Loading...

4-2 Protein Synthesis
Quiz by Jennifer Faulknor
Customize this quiz to suit your class
Instantly translate to 100+ languages
Tag the questions with any skills you have. Your dashboard will track each student's mastery of each skill.
Give this quiz to my class
The endoplasmic reticulum (EN-doh-PLAZ-mik ri-TIK-yuh-luhm), abbre- viated ER, is a system of membranous tubes and sacs, called cisternae (sis-TUHR-nee). The ER functions primarily as an intracellu- lar highway, a path along which molecules move from one part of the cell to another. The amount of ER inside a cell fluctuates, depending on the cell’s activity. There are two types of ER: rough and smooth. The two types of ER are thought to be continuous. Rough Endoplasmic Reticulum The rough endoplasmic reticulum is a system of interconnected, flattened sacs covered with ribosomes, as shown in Figure 4-15. The rough ER produces phospholipids and proteins. Certain types of proteins are made on the rough ER’s ribosomes. These proteins are later exported from the cell or inserted into one of the cell’s own membranes. For example, ribosomes on the rough ER make digestive enzymes, which accumulate inside the endoplasmic retic- ulum. Little sacs or vesicles then pinch off from the ends of the rough ER and store the digestive enzymes until they are released from the cell. Rough ER is most abundant in cells that produce large amounts of protein for export, such as cells in digestive glands and antibody-producing cells. Smooth Endoplasmic Reticulum The smooth ER lacks ribosomes and thus has a smooth appear- ance. Most cells contain very little smooth ER. Smooth ER builds lipids such as cholesterol. In the ovaries and testes, smooth ER produces the steroid hormones estrogen and testosterone. In skeletal and heart muscle cells, smooth ER releases calcium, which stimulates contraction. Smooth ER is also abundant in liver and kidney cells, where it helps detoxify drugs and poisons. Long-term abuse of alcohol and other drugs causes these cells to produce more smooth ER. Increased amounts of smooth ER in liver cells is one of the factors that can lead to drug tolerance. As Figure 4-15 shows, rough ER and smooth ER form an interconnected network. Copyright © by Holt, Rinehart and Winston. All rights reserved. reticulum from the Latin rete, meaning “net”; reticulum means “little net” Word Roots and Origins The endoplasmic reticulum (ER) serves as a site of synthesis for proteins, lipids, and other materials. The dark lines in the photo represent the membranes of the ER, and the narrow lighter areas between the dark lines show the channels and spaces (cisternae) inside the ER. FIGURE 4-15 Smooth ER Ribosomes Rough ER Cisternae 82 CHAPTER 4 GOLGI APPARATUS The Golgi apparatus, shown in Figure 4-16, is another system of flattened, membranous sacs. The sacs nearest the nucleus receive vesicles from the ER containing newly made proteins or lipids. Vesicles travel from one part of the Golgi apparatus to the next and transport substances as they go. The stacked membranes modify the vesicle contents as they move along. The proteins get “address labels” that direct them to various other parts of the cell. During this modification, the Golgi apparatus can add carbohydrate labels to proteins or alter new lipids in various ways. VESICLES Cells contain several types of vesicles, which perform various roles. Vesicles are small, spherically shaped sacs that are surrounded by a single membrane and that are classified by their contents. Vesicles often migrate to and merge with the plasma membrane. As they do, they release their contents to the outside of the cell. Lysosomes Lysosomes (LIE-suh-SOHMZ) are vesicles that bud from the Golgi appa- ratus and that contain digestive enzymes. These enzymes can break down large molecules, such as proteins, nucleic acids, car- bohydrates, and phospholipids. In the liver, lysosomes break down glycogen in order to release glucose into the bloodstream. Certain white blood cells use lysosomes to break down bacteria. Within a cell, lysosomes digest worn-out organelles in a process called autophagy (aw-TAHF-uh-jee). Lysosomes are also responsible for breaking down cells when it is time for the cells to die. The digestion of damaged or extra cells by the enzymes of their own lysosomes is called autolysis (aw-TAHL-uh-sis). Lysosomes play a very important role in maintaining an organism’s health by destroying cells that are no longer functioning properly. Copyright © by Holt, Rinehart and Winston. All rights reserved. The Golgi apparatus modifies many cellular products and prepares them for export. FIGURE 4-16 CELL STRUCTURE AND FUNCTION 83 Peroxisomes Peroxisomes are similar to lysosomes but contain different enzymes and are not produced by the Golgi apparatus. Peroxisomes are abundant in liver and kidney cells, where they neutralize free radicals (oxygen ions that can damage cells) and detoxify alcohol and other drugs. Peroxisomes are named for the hydrogen peroxide, H2O2, they produce when breaking down alco- hol and killing bacteria. Peroxisomes also break down fatty acids, which the mitochondria can then use as an energy source. Other Vesicles Specialized peroxisomes, called glyoxysomes, can be found in the seeds of some plants. They break down stored fats to provide energy for the developing plant embryo. Some cells engulf material by surrounding it with plasma membrane. The resulting pocket buds off to become a vesicle inside the cell. This vesicle is called an endosome. Lysosomes fuse with endosomes and digest the engulfed material. Food vacuoles are vesicles that store nutrients for a cell. Contractile vacuoles are vesicles that can contract and dispose of excess water inside a cell. Protein Synthesis One of the major functions of a cell is the production of protein. The path some proteins take from synthesis to export can be seen in Figure 4-17. In step , proteins are assembled by ribosomes on the rough ER. Then, in step , vesicles transport proteins to the Golgi apparatus. In step , the Golgi modifies proteins and pack- ages them in new vesicles. In step , vesicles release proteins that have destinations outside the cell. In step , vesicles containing enzymes remain inside the cell as lysosomes, peroxisomes, endo- somes, or other types of vesicles. 5 4 3 2 1 Copyright © by Holt, Rinehart and Winston. All rights reserved. Proteins are assembled by ribosomes on the rough ER. Vesicles carry proteins from the rough ER to the Golgi apparatus. Proteins are modified in the Golgi apparatus and enter new vesicles. Some vesicles release their proteins outside the cell. Other vesicles remain in the cell and become lysosomes and other vesicles. Nucleus
What is a Plant Cell? Plant cells are eukaryotic cells that vary in several fundamental factors from other eukaryotic organisms. Both plant and animal cells contain a nucleus along with similar organelles. One of the distinctive aspects of a plant cell is the presence of a cell wall outside the cell membrane. Plant Cell Structure Just like different organs within the body, plant cell structure includes various components known as cell organelles that perform different functions to sustain itself. These organelles include: Cell Wall It is a rigid layer which is composed of polysaccharides cellulose, pectin and hemicellulose. It is located outside the cell membrane. It also comprises glycoproteins and polymers such as lignin, cutin, or suberin. The primary function of the cell wall is to protect and provide structural support to the cell. The plant cell wall is also involved in protecting the cell against mechanical stress and providing form and structure to the cell. It also filters the molecules passing in and out of it. The formation of the cell wall is guided by microtubules. It consists of three layers, namely, primary, secondary and the middle lamella. The primary cell wall is formed by cellulose laid down by enzymes. Cell membrane It is the semi-permeable membrane that is present within the cell wall. It is composed of a thin layer of protein and fat. The cell membrane plays an important role in regulating the entry and exit of specific substances within the cell. For instance, cell membrane keeps toxins from entering inside, while nutrients and essential minerals are transported across. Nucleus The nucleus is a membrane-bound structure that is present only in eukaryotic cells. The vital function of a nucleus is to store DNA or hereditary information required for cell division, metabolism and growth. 1. Nucleolus: It manufactures cells’ protein-producing structures and ribosomes. 2. Nucleopore: Nuclear membrane is perforated with holes called nucleopore that allow proteins and nucleic acids to pass through. Plastids They are membrane-bound organelles that have their own DNA. They are necessary to store starch and to carry out the process of photosynthesis. It is also used in the synthesis of many molecules, which form the building blocks of the cell. Some of the vital types of plastids and their functions are stated below: Leucoplasts They are found in the non-photosynthetic tissue of plants. They are used for the storage of protein, lipid and starch. Chromoplasts They are heterogeneous, colored plastid which is responsible for pigment synthesis and for storage in photosynthetic eukaryotic organisms. Chromoplasts have red-, orange- and yellow-colored pigments which provide color to all ripe fruits and flowers. Central Vacuole It occupies around 30% of the cell’s volume in a mature plant cell. Tonoplast is a membrane that surrounds the central vacuole. The vital function of the central vacuole apart from storage is to sustain turgor pressure against the cell wall. The central vacuole consists of cell sap. It is a mixture of salts, enzymes and other substances. Golgi Apparatus They are found in all eukaryotic cells, which are involved in distributing synthesized macromolecules to various parts of the cell. Ribosomes They are the smallest membrane-bound organelles which comprise RNA and protein. They are the sites for protein synthesis, hence, also referred to as the protein factories of the cell. Mitochondria They are the double-membraned organelles found in the cytoplasm of all eukaryotic cells. They provide energy by breaking down carbohydrate and sugar molecules, hence they are also referred to as the “Powerhouse of the cell.” Lysosome Lysosomes are called suicidal bags as they hold digestive enzymes in an enclosed membrane. They perform the function of cellular waste disposal by digesting worn-out organelles, food particles and foreign bodies in the cell. In plants, the role of lysosomes is undertaken by the vacuoles. Chloroplasts It is an elongated organelle enclosed by phospholipid membrane. The chloroplast is shaped like a disc and the stroma is the fluid within the chloroplast that comprises a circular DNA. Each chloroplast contains a green colored pigment called chlorophyll required for the process of photosynthesis. The chlorophyll absorbs light energy from the sun and uses it to transform carbon dioxide and water into glucose. Structure of Chloroplast Chloroplasts are found in all higher plants. It is oval or biconvex, found within the mesophyll of the plant cell. The size of the chloroplast usually varies between 4-6 µm in diameter and 1-3 µm in thickness. They are double-membrane organelle with the presence of outer, inner and intermembrane space. There are two distinct regions present inside a chloroplast known as the grana and stroma. • Grana are made up of stacks of disc-shaped structures known as thylakoids or lamellae. The granum of the chloroplast consists of chlorophyll pigments and are the functional units of chloroplasts. • Stroma is the homogenous matrix which contains grana and is similar to the cytoplasm in cells in which all the organelles are embedded. Stroma also contains various enzymes, DNA, ribosomes, and other substances. Stroma lamellae function by connecting the stacks of thylakoid sacs or grana. The chloroplast structure consists of the following parts: Membrane Envelope It comprises inner and outer lipid bilayer membranes. The inner membrane separates the stroma from the intermembrane space. Intermembrane Space The space between inner and outer membranes. Thylakoid System (Lamellae) The system is suspended in the stroma. It is a collection of membranous sacs called thylakoids or lamellae. The green colored pigments called chlorophyll are found in the thylakoid membranes. It is the sight for the process of light-dependent reactions of the photosynthesis process. The thylakoids are arranged in stacks known as grana and each granum contains around 10-20 thylakoids. Stroma It is a colorless, alkaline, aqueous, protein-rich fluid present within the inner membrane of the chloroplast present surrounding the grana. Grana Stack of lamellae in plastids is known as grana. These are the sites of conversion of light energy into chemical energy. Chlorophyll It is a green photosynthetic pigment that helps in the process of photosynthesis. Functions of Chloroplast Following are the important chloroplast functions: • The most important function of the chloroplast is to synthesize food by the process of photosynthesis. • Absorbs light energy and converts it into chemical energy. • Chloroplast has a structure called chlorophyll which functions by trapping the solar energy and is used for the synthesis of food in all green plants. • Produces NADPH and molecular oxygen (O 2 ) by photolysis of water. • Produces ATP – Adenosine triphosphate by the process of photosynthesis. • The carbon dioxide (CO2) obtained from the air is used to generate carbon and sugar during the Calvin Cycle or dark reaction of photosynthesis. Mitochondria “Mitochondria are membrane-bound organelles present in the cytoplasm of all eukaryotic cells, that produce adenosine triphosphate (ATP), the main energy molecule used by the cell.” What are Mitochondria? Popularly known as the “Powerhouse of the cell,” mitochondria (singular: mitochondrion) are a double membrane-bound organelle found in most eukaryotic organisms. They are found inside the cytoplasm and essentially function as the cell’s “digestive system.” They play a major role in breaking down nutrients and generating energy-rich molecules for the cell. Many of the biochemical reactions involved in cellular respiration take place within the mitochondria. The term ‘mitochondrion’ is derived from the Greek words “mitos” and “chondrion” which means “thread” and “granules-like”, respectively. It was first described by a German pathologist named Richard Altmann in the year 1890. Structure of Mitochondria • The mitochondrion is a double-membraned, rod-shaped structure found in both plant and animal cell. • Its size ranges from 0.5 to 1.0 micrometers in diameter. • The structure comprises an outer membrane, an inner membrane, and a gel-like material called the matrix. • The outer membrane and the inner membrane are made of proteins and phospholipid layers separated by the intermembrane space. • The outer membrane covers the surface of the mitochondrion and has a large number of special proteins known as porins. Cristae The inner membrane of mitochondria is rather complex in structure. It has many folds that form a layered structure called cristae, and this helps in increasing the surface area inside the organelle. The cristae and the proteins of the inner membrane aid in the production of ATP molecules. The inner mitochondrial membrane is strictly permeable only to oxygen and ATP molecules. A number of chemical reactions take place within the inner membrane of mitochondria. Mitochondrial Matrix The mitochondrial matrix is a viscous fluid that contains a mixture of enzymes and proteins. It also comprises ribosomes, inorganic ions, mitochondrial DNA, nucleotide cofactors, and organic molecules. The enzymes present in the matrix play an important role in the synthesis of ATP molecules. Functions of Mitochondria The most important function of mitochondria is to produce energy through the process of oxidative phosphorylation. It is also involved in the following process: 1. Regulates the metabolic activity of the cell 2. Promotes the growth of new cells and cell multiplication 3. Helps in detoxifying ammonia in the liver cells 4. Plays an important role in apoptosis or programmed cell death 5. Responsible for building certain parts of the blood and various hormones like testosterone and estrogen 6. Helps in maintaining an adequate concentration of calcium ions within the compartments of the cell 7. It is also involved in various cellular activities like cellular differentiation, cell signaling, cell senescence, controlling the cell cycle and in cell growth. Disorders Associated with Mitochondria Any irregularity in the way mitochondria function can directly affect human health, but often, it is difficult to identify because symptoms differ from person to person. Disorders of the mitochondria can be quite severe; in some cases, they can even cause an organ to fail.
Received: 26 November 2019 Revised: 10 January 2020 Accepted: 19 January 2020 DOI: 10.1111/obr.13005 PEDIATRICS/PHYSIOLOGY Adipokines: A gear shift in puberty Desirée Nieuwenhuis | Natàlia Pujol-Gualdo Amanda J. Kiliaan Department of Anatomy, Radboud university medical center, Donders Institute for Brain, Cognition and Behaviour, Preclinical Imaging Center PRIME, Nijmegen, The Netherlands Correspondence Amanda J. Kiliaan, PhD, Associate Professor, Department of Anatomy, Donders Institute for Brain, Cognition, and Behaviour, Preclinical Imaging Center PRIME, Radboud university medical center, 6500 HB Nijmegen, Geert Grooteplein 21N 6525 EZ Nijmegen, The Netherlands. Email: amanda.kiliaan@radboudumc.nl Funding information Europees Fonds voor Regionale Ontwikkeling (EFRO), Grant/Award Number: BriteN 2016 1 | INTRODUCTION The prevalence of obesity in adolescents and children is increasing in | Ilse A.C. Arnoldussen | Summary In this review, we discuss the role of adipokines in the onset of puberty in children with obesity during adrenarche and gonadarche and provide a clear and detailed overview of the biological processes of two major players, leptin and adiponectin. Adipokines, especially leptin and adiponectin, seem to induce an early onset of puberty in girls and boys with obesity by affecting the hypothalamic-pituitary- gonadal (HPG) axis. Moreover, adipokines and their receptors are expressed in the gonads, suggesting a role in sexual maturation and reproduction. All in all, adipokines may be a clue in understanding mechanisms underlying the onset of puberty in child- hood obesity and puberty onset variability. KEYWORDS adipokines, obesity, puberty 1,2 the age of 5 years were overweight or were with obesity in 2016, and 3 Obesity is defined by an excessive accumulation of white adipose tissue (WAT), and it is often indicated by a body mass index (BMI) 4 above 30. Two main types of adipose tissue were described: WAT and brown adipose tissue (BAT), which differ in morphology and func- 5-7 Ilse A.C. Arnoldussen and Amanda J. Kiliaan contributed equally to this work. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. © 2020 The Authors. Obesity Reviews published by John Wiley & Sons Ltd on behalf of World Obesity Federation Obesity Reviews. 2020;21:e13005. wileyonlinelibrary.com/journal/obr 1 of 10 https://doi.org/10.1111/obr.13005 alarming rates. Specifically, worldwide, 41 million children below this number is expected to increase to 70 million in 2025. obesity is associated with various severe health complications, includ- ing increased risk of diabetes mellitus type 2, hypertension, heart dis- eases, and disturbances in sex hormone levels. 5,6 and mitochondria and plays a role in thermogenesis. Adipocytes in tion. BAT consists of adipocytes containing multiple lipid droplets WAT contain only a few mitochondria and a single lipid droplet. Adipose tissue has several functions including the storage of energy, thermogenesis, and the production and secretion of adipokines Generally, two physiological processes, adrenarche and gonadarche, 11,24 Childhood 5,7,8 a key role in puberty onset. Puberty is known as a period through which the body changes physically, being a physiological process resulting in the maturation of children, i.e. they develop sexual characteristics and obtain reproduc- 9,11 Adipokines are involved in a number of physiological processes including blood pressure, metabo- lism, glucose, and vascular homeostasis and may play amongst others 8-10 (hormones, cytokines, and peptides). tive functions. between obesity and puberty,2,12-23 the biological mechanisms under- lying obesity and puberty onset remain unclear. Hereafter, we review in detail the role of adipokines in the onset of puberty in childhood obesity. Although many studies have shown associations 2 | INITIATION OF PUBERTY PHYSIOLOGICAL PROCESSES IN THE interact to regulate the onset of puberty. During adrenarche, the adrenal cortex secretes steroid hormones (including 2 of 10 NIEUWENHUIS ET AL. androstenedione, dehydroepiandrosterone, dehydroepiandrosterone sulfate (DHEAS), androstenedione, and cortisol), insulin-like growth factor, and growth hormone, which contribute to the pubertal insights on new genetic loci (e.g. melanocortin-4 receptor, mitochon- drial carrier 2, and mitogen-activated protein kinase 13) and on sev- eral pathways that regulate the timing of puberty; however, it partly 34 9,24,25 Both adrenarche and gonadarche are involved in the development growth spurt, body odor, skin oiliness, and skeletal maturation. explains puberty timing variation. Thereby, defining the role of 25 adipokines is of importance in elucidating the variability in puberty as the expression of adipokines is sex-specific and is altered with body composition, adiposity, and during growth spurts. Moreover, adipokines and their receptors are expressed in gonads and several brain regions suggesting involvement in the onset of puberty and sex- ual maturation. Lastly, adipokines interfere in processes regulating timing and duration of puberty, for instance in the HPA and HPG axes which are both key players during adrenarche and gonadarche. Involvement of adipokines in the onset of puberty and specifically in individuals with obesity will be further reviewed in the next 2,24 3 | Puberty onset in girls is assessed using different markers, such as thelarche (breast development), menarche (the start of of pubic hair. pituitary-gonadal (HPG) axis is activated,2,26 and several hormones have been identified to participate in the activation of the HPG axis During gonadarche (Figure 1), the hypothalamic- 2,27 Kisspeptin, neurokinin B, and dynorphin are released by specialized including kisspeptin, neurokinin B, dynorphin, leptin, and ghrelin. 28 key regulator of the pulsatile secretion of gonadotropin releasing neurons, the KNDy neurons in the hypothalamus. Kisspeptin is a 29,30 B stimulates, and dynorphin inhibits the release of kisspeptin, which hormone (GnRH) from the hypothalamus. In addition, neurokinin implies that both coordinate a pulsatile release of kisspeptin. 31 Sub- sections. sequently, the activated HPG axis induces the pituitary gland to secrete luteinising hormone (LH) and follicle stimulating hormone (FSH). As a result, gametogenesis occurs, and the gonads will release sex hormones. Consequently, secondary sex characteristics develop including breast development in girls and an increased testicular vol- 2,26,32 is possibly due to differences in levels of body fat, hypothalamic-pitui- THE ONSET OF PUBERTY IN GIRLS ume in boys. The age at puberty onset varies greatly among individuals, which 19 35 menstruation), and pubic hair development. 33 genome-wide association studies have provided important new tary-adrenal (HPA) axis activity, and genetic background. Recent The average age of However, this age differs between cultures and ethnicities, and since 1980, age at menarche is girls at start of menarche is 12.4 years. 36 significantly decreasing. 36-39 F I G U R E 1 Hormonal regulation in the initiation of puberty in boys and girls. The secretion of kisspeptin, neurokinin B, and dynorphin from KNDy neurons initiate the release of gonadotropin releasing hormone (GnRH) from the hypothalamus. This activates the pituitary gland to produce and secrete luteinising hormone (LH) and follicle stimulating hormone (FSH), which in turn stimulate the gonads to produce estrogen and testosterone in girls and boys, respectively 1467789x, 2020, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/obr.13005, Wiley Online Library on [10/03/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License NIEUWENHUIS ET AL. 3 of 10 T A B L E 1 Summary of included studies Authors Year Country Study Design Primary Outcome Sex Sample Size (n) Age (y) Data Collection Lian et al21 2019 China Cross-sectional Puberty starts earlier in Chinese Han girls with obesity compared with Chinese Han girls with normal weight. Girls 2996 9-19 2012 and 2013 Biro et al12 Lazzeri et al20 2018 USA 2018 Italy Longitudinal Cross-sectional Body mass index had a greater effect on age at menarche than did race and ethnicity. Girls 946 6-16 2004-2014 Li et al23 2018 China Longitudinal For both, boys and girls, a higher BMI (ie, overweight and obese) is associated with earlier onset of puberty Girls Girls Boys Girls 542 Deng et al22 Flom et al15 2017 China Cross-sectional Increased BMI is associated with early timing spermarche and menarche. Boys Girls Girls 1278258 9-15 2005-2012 He et al24 Holmgren et al17 2017 China 2017 Sweden Cross-sectional Longitudinal Onset of puberty is not related to obesity in boys. Boys Boys Girls Girls 782 7-17 972 929 5839 Kelly et al19 2017 UK 2016 Brazil 2016 USA Longitudinal prospective cohort Higher BMI in girls is associated with the onset of menstruation at an earlier age. 11 10-18 11-17 Barcellos Gemelli et al25 Cross-sectional Longitudinal Excess weight is associated with early age of menarche. Girls 727 2014 2003-2009 Glass et al16 Lee et al26 In girls, but not in boys, greater adiposity is associated with the earlier onset of puberty. Boys Girls 135 Cabrera et al27 Leonibus et al14 2014 USA 2013 Italy Cross-sectional Longitudinal Thelarche occurred earlier than recently reported, while age of menarche remained unchanged. Girls 610 3-17.9 2007 2005-2012 Currie et al13 2012 Europe, USA, Canada Cross-sectional Overweight/obesity during childhood predicts the early onset of puberty in girls. Girls 20410 11, 13, 15 2005-2006 2017 USA Prospective birth cohort Overweight/obese status at the age of 7 ye was associated with increased risk of early menarche 788 From birth to menarche occurred Pregnancies 1959-1966 2016 USA Cross-sectional Boys with overweight enter puberty earlier compared with boys with normal weight or obesity, while puberty starts later in boys with obesity compared with boys with normal weight and overweight. Boys 3872 6-16 2005-2010 Overweight during childhood shows a relation with the early onset of puberty in girls. 6535 4259 695 11 15 5.8-12.2 2009/2010 2013/2014 2014-2017 Higher BMI during childhood is associated with early puberty. 2008 and 2009 2000-2002 Obesity during childhood is related to the earlier onset of puberty. Boys Girls 84 123 71 (Continues) 1467789x, 2020, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/obr.13005, Wiley Online Library on [10/03/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 4 of 10 NIEUWENHUIS ET AL. 3.1 | Fat storage For the initiation of puberty, the timing of stimulation and/or inhibi- tion of different hormones is important, and additionally, a certain amount and distribution of body fat is needed in order to start menar- che, which emphasizes the importance of body fat. From an evolution- ary point of view, body fat increases in mammalian females during puberty onset, and it highlights the need to guarantee a healthy preg- 40 women with anorexia nervosa. particularly body fat localized predominantly on the gluteofemoral fat depots, is profoundly associated with start of menarche, more than nancy, offspring, and maternal survival. fat, sex-hormones, and neuroendocrine alterations can evolve in men- strual dysfunction, for instance, in women with severe obesity or in 41-43 44-46 to gluteofemoral fat depots suggesting that leptin may convey infor- amount of total body fat. mation on body fat distribution to the hypothalamus during puberty. An improper level of body Importantly, body fat distribution, Blood leptin levels are strongly related 45 3.2 | HPG axis The HPG axis is activated by the release of kisspeptin resulting in the release of GnRH from the hypothalamus, and LH and FSH from the pituitary gland. In girls, FSH is involved in the development of the folli- cles in the ovaries, and it promotes the secretion of estrogen. LH stim- ulates the production of androgen hormones and induces ovulation 48 9,47 the release of kisspeptin and neurokinin B, and kisspeptin thereby (Figure 1). The secretion of estrogen has an inhibitory effect on inhibits the GnRH release from the hypothalamus. pattern of GnRH is important for the regulation of the menstrual cycle. This roughly 28-day-cycle comprises several phases, including the follicular phase and luteal phase. During the follicular phase, increasing levels of FSH stimulate the maturation of follicles and the production of estrogen from the ovaries. This in turn inhibits the release of FSH from the pituitary gland. A high level of estrogen will induce the production of LH by the pituitary gland, resulting in ovula- tion. The matured follicle secretes progesterone thereby inhibiting the release of GnRH. When the corpus luteum is demolished, there is less 48 3.3 | Adipokines According to results from studies reported in Table 1, girls with obe- sity enter puberty earlier compared with girls with normal higher leptin concentrations inhibit the intake of food and increases inhibition of GnRH. As a consequence, the cycle will start again. whole process, starting from the activated HPG axis, results in the development of the secondary sex characteristics in girls including 9,47 thelarche and menarche. 13,14,16-23,49-51 weight. these girls might be found in the secretion of adipokines. For instance, leptin is positively associated with the amount of body fat. Generally, energy expenditure. 9,52-54 An explanation for the early onset of puberty in The expression This TABLE 1 (Continued) Authors Year Country Study Design Primary Outcome Sample Sex Size (n) Age (y) Data Collection Herman-Giddens et al28 2012 USA Cross-sectional Observed mean ages of beginning genital and pubic hair growth and early testicular volumes were earlier than in past studies, depending on the characteristic and race/ethnicity. Boys 4131 6-16 2005-2010 Sorensen et al29 Aksglaede et al30 2010 2009 Denmark Denmark Cross-sectional/longitudinal Longitudinal Puberty onset at earlier ages was associated with an increased BMI in boys. Boys 1528 5.8-19.9 1991-1993/2006-2008 1930-1969 Juul et al31 Ribeiro et al32 2007 2006 Denmark Portugal Retrospective cohort Cross-sectional Higher BMI is associated with early voice break. 11-15 10-15 1990-1999 Kaplowitz et al18 Abbreviation: BMI, body mass USA Cross-sectional The early onset of puberty in Caucasian girls is likely related to an increased BMI. 5-12 1992-1993 2001 index. The higher BMI in boys and girls at 7 y of age, the earlier they enter puberty. Boys 21 612 Girls 135 223 Boys 463 Boys 382 Girls 437 Girls 10 750 Early sexual maturation in boys and girls is associated with overweight. 1467789x, 2020, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/obr.13005, Wiley Online Library on [10/03/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License NIEUWENHUIS ET AL. 5 of 10 Leptin may possibly play a role in adrenarche as its plasma level increases with higher levels of body fat and as it can modulate both girls. 33 ing adrenarche. In coherence, in children with obesity, the androgen These findings suggested that lower reproductive status was associated with higher total adiponectin concentrations and that a higher reproductive status was related to higher HMW adiponectin the HPA and HPG axes. These axes are functionally integrated dur- DHEAS was positively associated with leptin levels. Nevertheless, concentrations in girls. In addition, individuals with obesity often another study showed that enhanced adrenal androgen secretion in girls with premature adrenarche was not explained by leptin or BMI 55 ated with androgen levels in girls ; however, it was not related to levels. and IL-6. TNF-α alters, and IL-6 inhibits the expression of 56 8 In addition, the adipokine adiponectin was negatively associ- 57 differences of adiponectin seem to develop during the progression of 56 adiponectin (Figure 2). Thereby, a low level of total adiponectin and/or high levels of inflammatory cytokines in individuals with obe- sity can promote the onset of puberty. Many more adipokines are secreted by WAT including omentin, 52,65-67 9,36,62,68 adrenarche in girls with Prader-Willi syndrome. Interestingly, sex puberty. adrenarche; however, both are not required factors. Thus, leptin and adiponectin might be able to influence In gonadarche, leptin can stimulate the secretion of kisspeptin, and subsequently activation of the HPG axis, which eventually increases the expression of estrogen and androstenedione in the ova- 58 2,60 65-67 The expression of these ries (Figure 2). Ob gene in WAT, resulting in the synthesis and secretion of leptin. Thus, high levels of leptin promote onset of puberty in girls via secre- tion of kisspeptin, and estrogen stimulates leptin secretion addition- ally. Moreover, adiponectin can affect the HPG axis due to the expression of adiponectin receptors in the hypothalamus, pituitary In return, estrogen stimulates the expression of the 59 gland, and gonads. onset as it inhibits the secretion of kisspeptin and GnRH in the hypo- thalamus and the release of GH and LH in the pituitary gland, and 2,60-62 52,60 63 girls with central precocious puberty (CPP). Moreover, total adiponectin had negative correlations with progression of puberty in girls (defined by Tanner stages), whereas HMW adiponectin had FIGURE 2 Adipokinesaffectingthe initiation of puberty in girls. Leptin stimulates the release of kisspeptin in KNDy neurons, which activates the hypothalamus to produce gonadotropin releasing hormone (GnRH). In response to the release of GnRH, the pituitary gland secretes follicle stimulating hormone (FSH) and luteinising hormone (LH), which stimulates the ovaries to release estrogen resulting in the formation of secondary sex characteristics in girls. Estrogen stimulates the production of leptin. Adiponectin inhibits GnRH release resulting in reduced levels of GnRH and thereby a delayed onset of puberty. TNF- α and IL-6 inhibit the production of adiponectin and therefore stimulate the onset of puberty In detail, adiponectin is a regulator of puberty thereby inhibiting the onset of puberty (Figure 2). with obesity often have low levels of adiponectin. et al. showed that total adiponectin was significantly lower, whereas high molecular weight (HMW) adiponectin was significantly higher in ment. 55 63 develop a chronic low-grade inflammatory state, which can be indi- cated by a high level of circulating inflammatory cytokines like TNF-α 64 Individuals Sitticharoon positive associations with LH levels and the progression of puberty in 63 visfatin, resistin, and chemerin. and visfatin are expressed in the ovaries. adipokines in the ovaries suggests a role within the reproductive sys- tem; however, the exact biological processes have to be examined. Thus, specifically leptin, adiponectin, and inflammatory cytokines pro- duced by WAT could be permissive key players during an early onset of puberty in girls with obesity. As an exception, HMW adiponectin seems to have a stimulatory effect on peripheral repro- ductive function as HMW is not able to cross the blood brain 63 barrier. 4 | Markers that are used to assess puberty onset in boys are THE ONSET OF PUBERTY IN BOYS spermarche, voice break, testicular volume, and pubic hair develop- 35 spermarche develop in the early stages of puberty onset, voice In women, omentin, chemerin, While pubic hair development, larger testicular volume, and 69 testicular volume increases, which occurs at an average age of break usually appears in later stages of puberty. Generally, first 1467789x, 2020, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/obr.13005, Wiley Online Library on [10/03/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 6 of 10 NIEUWENHUIS ET AL. 11.9 years, followed by the development of pubic hair at 12.2 years of average, and lastly, boys experience spermarche around an aver- 55 related with leptin levels. Thereby, leptin plausibly has a minor impact in adrenarche in boys. Since leptin receptors are found in the hypothalamus, pituitary gland, and testes, they might be involved in the onset of puberty by affecting the HPG axis during gonadarche. Leptin stimulates the release of kisspeptin and GnRH, and as a consequence, it accelerates the onset of puberty (Table 1, Figure 3). In contrast, adiponectin inhibits the secretion of GnRH, GH, LH, and FSH therewith delaying the onset of puberty. However, adiponectin levels are generally lower in men compared with women and even lower in men with obe- age age of 13.4 years. 70 4.1 | Fat storage Many aspects of the reproductive physiology are energetically demanding,71 and therefore, an adequate energy level is necessary. In boys, a dynamic change in body composition occurs around the age of 10 to 13 years, in which they gain approximately 40% of sity. culating inflammatory cytokines. levels can stimulate the HPG axis and therewith an early onset of puberty in boys. Nevertheless, leptin can inhibit the production of tes- 72 mostly consisting of lean mass, which causes exhaustion of most of fat. Subsequently, a growth spurt follows in which they gain tissue 72 in boys, an adequate amount of body fat is important in the onset of their body fat. These alterations in amount of body fat indicate that 4.2 | Puberty in boys is initiated by the release of kisspeptin. As mentioned before, this activates the HPG axis, resulting in the release of GnRH from the hypothalamus, and consequently the release of LH and FSH 9,74 puberty. tosterone from the testes, to estrogen (Figure 3). of the development of secondary sex characteristics in boys. Additionally, leptin can affect fertility in men as it can modulate the nutritional support of spermatogenesis, and moreover, dysfunction of spermatogenesis is associated with an increased leptin level and 73 58 2,60-62 HPG axis from the pituitary gland (Figure 1). and LH stimulates the secretion of testosterone from the testes, which inhibits the release of kisspeptin from the KNDy neurons and 9,48 in men, the release of kisspeptin is more consistent, causing a con- 29,48 subsequently GnRH from the hypothalamus. receptors expressed on KNDy neurons. In humans, KNDy neurons Contrarily to women, LH-induced testosterone levels lead to the stant release of LH. development of secondary sex characteristics in boys. differences between sexes in kisspeptin release are related to a sex- specific and sex steroid-dependent kisspeptin system as estrogen and progesterone modulate kisspeptin activity through the sex-steroid 48 in the infundibular nucleus are involved in negative and positive sex- 48 tal exposure to sex steroids and result in sex-specific differences in steroid feedbacks. kisspeptin release. These sexual dimorphisms are induced by perina- 75,76 4.3 | Adipokines The association between obesity and puberty onset in boys is rather controversial compared with findings in girls. Most studies reported an early onset of puberty in boys associated with increased ate adipose tissue from actual breast tissue. stages are more difficult to assess than female stages as boys lack a more determined marker such as menarche. Thirdly, puberty onset can be indicated by the activation of the HPG axis, and the presence of these secondary sex characteristics is the result of hormonal 2 14,17,22,23,50,51,77,78 BMI, 20,49 all while others reported no associations at Current markers used 79 16,80 or a delayed onset of puberty (Table 1). The presence of excessive adipose tissue can be involved in puberty onset in boys as the secretion of adipokines can modulate both adrenarche and gonadarche. Leptin can affect adrenarche by modulating both the HPG and HPA axes,33 and moreover, androgen levels were positively 55 nal androgen secretion in boys with premature adrenarche was not associated with plasma leptin levels. Nevertheless, enhanced adre- 9 In more detail, 61,62 adiponectin, and individuals with obesity often have high levels of cir- Moreover, inflammatory cytokines, TNF-α, and IL-6, inhibit expression of the leptin receptor in the testis. FSH induces spermatogenesis, too. function and role still have to be examined. 64 High leptin and low adiponectin and fat tissue can convert testosterone Both processes might result in the delay 29,61,79 81,82 In men, other adipokines like chemerin are found in the gonads 65 Thus, particularly high leptin and low adiponectin levels stimulate the HPG axis and thereby accelerate the onset of puberty in boys. Additionally, leptin can dysregulate the development of secondary sex characteristics and spermatogenesis by affecting testosterone levels and nutritional sup- port of spermatogenesis. 5 | LIMITATIONS AND FUTURE RESEARCH DIRECTIONS Even though multiple epidemiological studies have shown the link between puberty onset and obesity, there are some important limita- tions. Firstly, determining both the onset and stage of puberty is rather difficult. For instance, assessing the stage of breast develop- ment in girls with obesity is complicated as clinicians should differenti- 2 changes in response to the activated HPG axis. to determine the onset of puberty refer to secondary sex characteris- tics, such as testicular volume in boys and breast development in girls. A more accurate measurement of puberty onset would be to combine secondary sex characteristics with plasma or serum hormone level measurements such as LH, FSH, adipokines, e.g. leptin. Thereby, differences in puberty measurements could explain variations in the age of puberty onset between boys and girls within different Thereby, resistin is expressed in the testes of rats, but its exact 83 Secondly, male pubertal 1467789x, 2020, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/obr.13005, Wiley Online Library on [10/03/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License NIEUWENHUIS ET AL. 7 of 10 FIGURE 3 Adipokines affecting the initiation of puberty in boys. Leptin activates kisspeptin secretion in KNDy neurons, this activates the production of gonadotropin releasing hormone (GnRH) from the hypothalamus. GnRH stimulates the pituitary gland to secrete follicle stimulating hormone (FSH) and luteinising hormone (LH), activating the production of testosterone from the testes allowing the development of secondary sex characteristics. Leptin also inhibits the production of testosterone, which may cause a delayed onset of puberty. Adiponectin inhibits GnRH release. Low levels of adiponectin, as a result of TNF-α and IL-6 expression, lead to a reduced inhibition of GnRH. In response to GnRH release, the pituitary gland will secrete FSH and LH, and the testes will produce testosterone resulting in the development of secondary sex characteristics in boys countries, and In addition, the inclusion of a of puberty. ferent time points is complicated, as subjects examined several decades ago presented pronounced differences concerning lifestyle patterns such as nutrition and exercise habits. Lastly, obesity or over- weight is often determined by BMI, a classification based on weight and height measurements. Additionally, it is important that all studies studies or across continents, ethnicities proper age range (8-16 years) is important when assessing the onset (Figure 4). 12-15,17,20-23,49,77-79,84,85 30,47 Furthermore, comparison between studies from dif- 86 Specifically in children, BMI is often dependent on age and growth use the same anthropometric standards and sex-specific cut-offs. 13,14,16-23,49-51,77-80 fat and would represent a more accurate measurement in its regard. Based on this review, several suggestions can be made for further research. Firstly, the roles of adipokines like resistin, chemerin, visfatin, and omentin in puberty onset, fertility, and sexual maturation should be examined in detail. Secondly, future research examining the onset of puberty should combine indicators of puberty onset (e.g. breast development or testicular volume) with plasma or serum hor- mone measurements such as LH, FSH, sex-steroids, adipokines (e.g. spurts. ment in case of growth spurts. distribution of body fat should be taken into account in determining puberty and obesity in children. For instance, the body adiposity index (BAI), which was introduced in 2011 by Bergman et al.,87 uses hip cir- cumference and height in order to estimate the percentage of body 87 Thereby, BMI is a less accurate measure- F I G U R E 4 87,88 Therefore, both percentage and Average age of puberty onset in Europe, China, and the United States according to several studies from Table 1. Age of puberty onset ranges from 8.47 to 13.33 years in girls and from 8.63 leptin), and body fat distribution (e.g. BAI,87 waist-hip ratio's and/or dual-energy X-ray absorptiometry (DXA)2). Additionally, defining con- sistent and general measurements of puberty in both boys and girls, combined with a proper age range (8-16 years), would facilitate the comparisons between different studies and their results. 12-15, 17, 20-23, 25-29, 31 to 13.7 years in boys. included if average age of markers used to assess puberty was not reported. Pink: girls. Blue: boys Studies (Table 1) were not 39, 56 1467789x, 2020, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/obr.13005, Wiley Online Library on [10/03/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 8 of 10 NIEUWENHUIS ET AL. 6 | CONCLUSION In conclusion, epidemiological data regarding obesity and puberty onset in girls show similar outcomes as adiposity results in the early onset of puberty in girls. The majority of the studies examining boys with obesity indicate an early onset of puberty, while not all reported an earlier onset of puberty. In detail, high leptin, TNF-α, and IL-6 levels combined with low adiponectin levels stimulate the activation of the HPG axis in girls and boys with obesity, and 5, 45, 50, 51 REFERENCES 1. Kumar S, Kelly AS. Review of childhood obesity: from epidemiology, etiology, and comorbidities to clinical assessment and treatment. May- o Clin Proc. 2017;92(2):251-265. 2. Reinehr T, Roth CL. Is there a causal relationship between obesity and puberty? The Lancet Child & adolescent health. 2019;3(1):44-54. 3. WorldHealthOrganization. Facts and figures on childhood obesity. 2017. 4. Guglielmi V, Sbraccia P. Obesity phenotypes: depot-differences in adipose tissue and their clinical implications. Eat Weight Disord. 2018; 23(1):3-14. 5. Gomez-Hernandez A, Beneit N, Diaz-Castroverde S. Escribano O. Dif- ferential role of adipose tissues in obesity and related metabolic and vas- cular complications. 2016;2016:1-15, 1216783. 6. Zwick RK, Guerrero-Juarez CF, Horsley V, Plikus MV. Anatomical, physiological, and functional diversity of adipose tissue. Cell Metab. 2018;27(1):68-83. 7. Gulyaeva O, Dempersmier J, Sul HS. Genetic and epigenetic control of adipose development. Biochimica et Biophysica Acta (BBA)— Molecular and Cell Biology of Lipids. 2019;1864:3-12. 8. Khan M, Joseph F. Adipose tissue and adipokines: the association with and application of adipokines in obesity. Forensic Sci. 2014;2014: 711-724, 328592. 9. Alotaibi MF. Physiology of puberty in boys and girls and pathological disorders affecting its onset. J Adolesc. 2019;71:63-71. 10. Cousminer DL, Stergiakouli E, Berry DJ, et al. Genome-wide associa- tion study of sexual maturation in males and females highlights a role for body mass and menarche loci in male puberty. Hum Mol Genet. 2014;23(16):4452-4464. 11. Ahmed ML, Ong KK, Dunger DB. Childhood obesity and the timing of puberty. Trends in endocrinology and metabolism: TEM. 2009;20(5): 237-242. 12. Biro FM, Pajak A, Wolff MS, et al. Age of menarche in a longitudinal US cohort. J Pediatr Adolesc Gynecol. 2018;31(4):339-345. 13. Currie C, Ahluwalia N, Godeau E, Nic Gabhainn S, Due P, Currie DB. Is obesity at individual and national level associated with lower age at menarche? Evidence from 34 countries in the Health Behaviour in School-aged Children Study. The Journal of adolescent health: official publication of the Society for Adolescent Medicine. 2012;50(6): 621-626. 14. De Leonibus C, Marcovecchio ML, Chiavaroli V, de Giorgis T, Chiarelli F, Mohn A. Timing of puberty and physical growth in obese children: a longitudinal study in boys and girls. Pediatr Obes. 2014; 9(4):292-299. 15. Flom JD, Cohn BA, Tehranifar P, et al. Earlier age at menarche in girls with rapid early life growth: cohort and within sibling analyses. Ann Epidemiol. 2017;27(3):187-93.e2. 16. Glass NA, Torner JC, Letuchy EM, et al. The relationship between greater prepubertal adiposity, subsequent age of maturation, and bone strength during adolescence. Journal of bone and mineral research: the official journal of the American Society for Bone and Min- eral Research. 2016;31(7):1455-1465. 17. Holmgren A, Niklasson A, Nierop AF, et al. Pubertal height gain is inversely related to peak BMI in childhood. Pediatr Res. 2017;81(3): 448-454. 18. Kaplowitz PB, Slora EJ, Wasserman RC, Pedlow SE, Herman- Giddens ME. Earlier onset of puberty in girls: relation to increased body mass index and race. Pediatrics. 2001;108(2):347-353. 19. Kelly Y, Zilanawala A, Sacker A, Hiatt R, Viner R. Early puberty in 11-year-old girls: Millennium Cohort Study findings. Arch Dis Child. 2017;102(3):232-237. 20. Lazzeri G, Tosti C, Pammolli A, et al. Overweight and lower age at menarche: evidence from the Italian HBSC cross-sectional survey. BMC Womens Health. 2018;18(1):168-174. thereby an early onset of obesity. leptin can inhibit the production of testosterone in boys and subse- quently inhibit the development of secondary sex characteristics affecting spermatogenesis. for other adipokines, like resistin and omentin, are present in the testes and ovaries suggesting a role in puberty or reproduction; 58, 71 however, their plausible function is still unknown. that adipokines may be key regulators in an early onset of puberty in both girls and boys with obesity, specifically by affecting the HPG axis during gonadarche. Future research should focus on assessing puberty onset by measuring consistent puberty markers and determine the percentage of body fat and its distribution and adipokines and hormone serum levels particularly involved in the HPG axis. CONFLICTS OF INTEREST The authors declare no conflict of interest. FUNDING INFORMATION This research was funded by Europees Fonds voor Regionale Ontwikkeling (EFRO), project BriteN 2016. ORCID Ilse A.C. Arnoldussen Amanda J. Kiliaan https://orcid.org/0000-0002-7395-5284 https://orcid.org/0000-0002-2158-6210 13, 14, 16-26, 29-32 Furthermore, several receptors Nevertheless, We conclude Search strategy We searched PubMed for articles published before Novem- ber 15th, 2019 using relevant keywords, including ‘onset of puberty and adiposity/obesity’, ‘onset of puberty’, ‘children with obesity’, ‘adipose tissue’, ‘childhood obesity’, ‘adiposity’, ‘obesity’, ‘adipokine(s)’, ‘HPG axis’, ‘adipokines ovary/ova- ries’, or ‘adipokines testes’, either alone or in combination. Selection criteria used were English language, longitudinal or cross-sectional studies assessing the onset of puberty, including menarche, thelarche, spermarche, or voice break, combined with high BMI or obesity/adiposity, and articles assessing or reviewing adipokines and its effects on the reproductive system. 1467789x, 2020, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/obr.13005, Wiley Online Library on [10/03/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License NIEUWENHUIS ET AL. 9 of 10 21. Lian Q, Mao Y, Luo S, et al. Puberty timing associated with obesity and central obesity in Chinese Han girls. BMC Pediatr. 2019; 19(1):1-7. 22. Deng Y, Liang J, Zong Y, et al. Timing of spermarche and menarche among urban students in Guangzhou, China: trends from 2005 to 2012 and association with Obesity. Sci Rep. 2018;8(1):263-270. 23. Li W, Liu Q. Association of prepubertal obesity with pubertal devel- opment in Chinese girls and boys: a longitudinal study. 2018;30: e23195. 24. Mendle J, Beltz AM, Carter R, Dorn LD. Understanding puberty and its measurement: ideas for research in a new generation. Journal of research on adolescence: the official journal of the Society for Research on Adolescence. 2019;29(1):82-95. 25. Pagani S, Meazza C, Gertosio C, Bozzola E, Bozzola M. Growth hor- mone receptor gene expression in puberty. Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme. 2015;47:581-584. 26. Abreu AP, Kaiser UB. Pubertal development and regulation. Lancet Diabetes Endocrinol. 2016;4(3):254-264. 27. Aguirre RS, Eugster EA. Central precocious puberty: from genetics to treatment. Best Pract Res Clin Endocrinol Metab. 2018;32(4): 343-354. 28. Sultan C, Gaspari L, Maimoun L, Kalfa N, Paris F. Disorders of puberty. Best Pract Res Clin Obstet Gynaecol. 2018;48:62-89. 29. Skorupskaite K, George JT, Anderson RA. The kisspeptin-GnRH path- way in human reproductive health and disease. Hum Reprod Update. 2014;20(4):485-500. 30. Dahl SK, Amstalden M, Coolen L, Fitzgerald M, Lehman M. Dynorphin immunoreactive fibers contact GnRH neurons in the human hypothal- amus. Reprod Sci. 2009;16(8):781-787. 31. Navarro VM, Gottsch ML, Chavkin C, Okamura H, Clifton DK, Steiner RA. Regulation of gonadotropin-releasing hormone secretion by kisspeptin/dynorphin/neurokinin B neurons in the arcuate nucleus of the mouse. J Neurosci. 2009;29(38):11859-11866. 32. Zhai L, Liu J, Zhao J, et al. Association of obesity with onset of puberty and sex hormones in chinese girls: a 4-year longitudinal study. PLoS ONE. 2015;10(8):1-12, e0134656. 33. Cizza G, Dorn LD, Lotsikas A, Sereika S, Rotenstein D, Chrousos GP. Circulating plasma leptin and IGF-1 levels in girls with premature adrenarche: potential implications of a preliminary study. Horm Metab Res. 2001;33(3):138-143. 34. Cousminer DL, Widén E, Palmert MR. The genetics of pubertal timing in the general population: recent advances and evidence for sex-spec- ificity. Curr Opin Endocrinol Diabetes Obes. 2016;23(1):57-65. 35. Marshall WA, Tanner JM. Variations in pattern of pubertal changes in girls. Arch Dis Child. 1969;44(235):291-303. 36. Lacroix AE, Whitten R. Physiology. Treasure Island (FL): Menarche. StatPearls. StatPearls Publishing; 2018. 37. McDowell MA, Brody DJ, Hughes JP. Has Age at Menarche Chan- ged? Results from the National Health and Nutrition Examination Sur- vey (NHANES) 1999–2004. J Adolesc Health. 2007;40(3):227-231. 38. de Muinich Keizer SM, Mul D. Trends in pubertal development in Europe. Hum Reprod Update. 2001;7(3):287-291. 39. Talma H, Schönbeck Y, van Dommelen P, Bakker B, van Buuren S, Hirasing RA. Trends in menarcheal age between 1955 and 2009 in the Netherlands. PLoS ONE. 2013;8:e60056-e60056. 40. Kaplan HS, Lancaster JB. An evolutionary and ecological analysis of human fertility, mating patterns, and parental investment. Off- spring: Human fertility behavior in biodemographic perspective. 2003;1: 170-223. 41. Mitan LA. Menstrual dysfunction in anorexia nervosa. J Pediatr Adolesc Gynecol. 2004;17(2):81-85. 42. Xu H, Li P-H, Barrow TM, et al. Obesity as an effect modifier of the association between menstrual abnormalities and hypertension in young adult women: Results from Project ELEFANT. PLoS ONE. 2018; 13(11):e0207929-e0207929. 43. Tauqeer Z, Gomez G, Stanford FC. Obesity in women: insights for the clinician. J Womens Health (Larchmt). 2018;27(4):444-457. 44. de Ridder CM, Thijssen JH, Bruning PF, Van den Brande JL, Zonderland ML, Erich WB. Body fat mass, body fat distribution, and pubertal development: a longitudinal study of physical and hormonal sexual maturation of girls. J Clin Endocrinol Metab. 1992;75(2): 442-446. 45. Lassek W, Gaulin S. Brief communication: menarche is related to fat distribution. Am J Phys Anthropol. 2007;133(4):1147-1151. 46. Loomba-Albrecht LA, Styne DM. Effect of puberty on body composi- tion. Curr Opin Endocrinol Diabetes Obes. 2009;16:10-15. 47. Simonneaux V, Bahougne T. A multi-oscillatory circadian system times female reproduction. Front Endocrinol. 2015;6:1-15. 48. Marques P, Skorupskaite K, George JT, Anderson RA. Physiology of GNRH and gonadotropin secretion. In: Feingold KR, Anawalt B, Boyce A, et al., eds. Endotext. Endotext.org: South Dartmouth (MA); 2000. 49. Barcellos Gemelli IF, Farias EDS, Souza OF. Age at menarche and its association with excess weight and body fat percentage in girls in the Southwestern Region of the Brazilian Amazon. J Pediatr Adolesc Gynecol. 2016;29(5):482-488. 50. Aksglaede L, Juul A, Olsen LW, Sorensen TI. Age at puberty and the emerging obesity epidemic. PLoS ONE. 2009;4:1-6, e8450. 51. Ribeiro J, Santos P, Duarte J, Mota J. Association between over- weight and early sexual maturation in Portuguese boys and girls. Ann Hum Biol. 2006;33(1):55-63. 52. Budak E, Fernandez Sanchez M, Bellver J, Cervero A, Simon C, Pellicer A. Interactions of the hormones leptin, ghrelin, adiponectin, resistin, and PYY3-36 with the reproductive system. Fertil Steril. 2006;85(6):1563-1581. 53. Castellano JM, Tena-Sempere M. Metabolic control of female puberty: potential therapeutic targets. Expert Opin Ther Targets. 2016; 20(10):1181-1193. 54. Venancio JC, Margatho LO, Rorato R, et al. Short-term high-fat diet increases leptin activation of CART neurons and advances puberty in female mice. Endocrinology. 2017;158(11):3929-3942. 55. l'Allemand D, Schmidt S, Rousson V, Brabant G, Gasser T, Gruters A. Associations between body mass, leptin, IGF-I and circulating adrenal androgens in children with obesity and premature adrenarche. Eur J Endocrinol. 2002;146(4):537-543. 56. Böttner A, Jr K, Müller G, et al. Gender Differences of adiponectin levels develop during the progression of puberty and are related to serum androgen levels. J Clin Endocrinol Metabol. 2004;89(8):4053- 4061. 57. Unanue N, Bazaes R, Iñiguez G, Cortes F, Avila A, Mericq V. Adre- narche in Prader-Willi syndrome appears not related to insulin sensi- tivity and serum adiponectin. Horm Res. 2007;67(3):152-158. 58. Michalakis K, Mintziori G, Kaprara A, Tarlatzis BC, Goulis DG. The complex interaction between obesity, metabolic syndrome and repro- ductive axis: a narrative review. Metabolism: clinical and experimental. 2013;62(4):457-478. 59. Machinal-Quelin F, Dieudonne MN, Pecquery R, Leneveu MC, Giudicelli Y. Direct in vitro effects of androgens and estrogens on ob gene expression and leptin secretion in human adipose tissue. Endo- crine. 2002;18(2):179-184. 60. Dobrzyn K, Smolinska N, Kiezun M. Adiponectin: A new regulator of female reproductive system. Int J Endocrinol. 2018;2018:1-12, 7965071. 61. Martin LJ. Implications of adiponectin in linking metabolism to testic- ular function. Endocrine. 2014;46(1):16-28. 62. Mathew H, Castracane VD, Mantzoros C. Adipose tissue and repro- ductive health. Metabolism: clinical and experimental. 2018;86:18-32. 1467789x, 2020, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/obr.13005, Wiley Online Library on [10/03/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 10 of 10 NIEUWENHUIS ET AL. 63. Sitticharoon C, Sukharomana M, Likitmaskul S, Churintaraphan M, Maikaew P. Corrigendum to: Increased high molecular weight adiponectin, but decreased total adiponectin and kisspeptin, in central precocious puberty compared with aged-matched prepubertal girls. Reprod Fertil Dev. 2017;29:2506-2517. 64. Das UN. Is obesity an inflammatory condition? Nutrition. 2001; 17(11-12):953-966. 65. Comninos AN, Jayasena CN, Dhillo WS. The relationship between gut and adipose hormones, and reproduction. Hum Reprod Update. 2014; 20(2):153-174. 66. Singh A, Choubey M, Bora P, Krishna A. Adiponectin and chemerin: contrary adipokines in regulating reproduction and metabolic disor- ders. Reproductive sciences (Thousand Oaks, Calif). 2018;25:1462- 1473. 67. Tsatsanis C, Dermitzaki E, Avgoustinaki P, Malliaraki N, Mytaras V, Margioris AN. The impact of adipose tissue-derived factors on the hypothalamic-pituitary-gonadal (HPG) axis. Hormones (Athens). 2015; 14:549-562. 68. Kang MJ, Oh YJ, Shim YS, Baek JW, Yang S. Hwang IT. The usefulness of circulating levels of leptin, kisspeptin, and neurokinin B in obese girls with precocious puberty. 2018;34:627-630. 69. Lee J, Song J, Hootman JM, et al. Obesity and other modifiable fac- tors for physical inactivity measured by accelerometer in adults with knee osteoarthritis: data from the osteoarthritis initiative (OAI). Arthritis Care Res (Hoboken). 2012;53-61. 70. Bramswig J, Dubbers A. Disorders of pubertal development. Deutsches Arzteblatt international. 2009;106:295-303. quiz 04 71. Elias CF, Purohit D. Leptin signaling and circuits in puberty and fertil- ity. Cell Mol Life Sci. 2013;70(5):841-862. 72. Riumallo J, Durnin JV. Changes in body composition in adolescent boys. Eur J Clin Nutr. 1988;42(2):107-112. 73. Siervogel RM, Demerath EW, Schubert C, et al. Puberty and body composition. Horm Res. 2003;60(Suppl 1):36-45. 74. Zhang J. Gong M. Andrologia: Review of the role of leptin in the regu- lation of male reproductive function; 2018. 75. Kauffman AS, Gottsch ML, Roa J, et al. Sexual differentiation of Kiss1 gene expression in the brain of the rat. Endocrinology. 2007;148(4): 1774-1783. 76. Zeydabadi Nejad S, Ramezani Tehrani F, Zadeh-Vakili A. The role of kisspeptin in female reproduction. Int J Endocrinol Metab. 2017;15:1- 11, e44337. 77. Sorensen K, Aksglaede L, Petersen JH, Juul A. Recent changes in pubertal timing in healthy Danish boys: associations with body mass index. J Clin Endocrinol Metab. 2010;95(1):263-270. 78. Juul A, Magnusdottir S, Scheike T, Prytz S, Skakkebaek NE. Age at voice break in Danish boys: effects of pre-pubertal body mass index and secular trend. Int J Androl. 2007;30(6):537-542. 79. Lee JM, Wasserman R, Kaciroti N, et al. Timing of puberty in overweight versus obese boys. Pediatrics. 2016;137(2):137-146, e20150164. 80. He F, Guan P, Liu Q, Crabtree D, Peng L, Wang H. The relationship between obesity and body compositions with respect to the timing of puberty in Chongqing adolescents: a cross-sectional study. BMC Pub- lic Health. 2017;17:664-673. 81. Ishikawa T, Fujioka H, Ishimura T, Takenaka A, Fujisawa M. Expres- sion of leptin and leptin receptor in the testis of fertile and infertile patients. Andrologia. 2007;39(1):22-27. 82. Martins AD, Moreira AC, Sa R, et al. Leptin modulates human Sertoli cells acetate production and glycolytic profile: a novel mechanism of obesity-induced male infertility? Biochim Biophys Acta. 1852;2015: 1824-1832. 83. Morash BA, Willkinson D, Ur E, Wilkinson M. Resistin expression and regulation in mouse pituitary. FEBS Lett. 2002;526(1-3):26-30. 84. Cabrera SM, Bright GM, Frane JW, Blethen SL, Lee PA. Age of thelarche and menarche in contemporary US females: a cross- sectional analysis. Journal of pediatric endocrinology & metabolism: JPEM. 2014;27(1-2):47-51. 85. Herman-Giddens ME, Steffes J, Harris D, et al. Secondary sexual characteristics in boys: data from the Pediatric Research in Office Settings Network. Pediatrics. 2012;130(5):e1058-e1068. 86. WHO. Physical status: the use and interpretation of anthropometry. Report of a WHO Expert Committee. World Health Organ Tech Rep Ser. 1995;854:1-452. 87. Akin I, Tolg R, Hochadel M, et al. No evidence of “obesity paradox” after treatment with drug-eluting stents in a routine clinical practice: results from the prospective multicenter German DES.DE (German Drug-Eluting Stent) Registry. JACC Cardiovasc Interv. 2012;5(2): 162-169. 88. Marcovecchio ML, Chiarelli F. Obesity and growth during childhood and puberty. World Rev Nutr Diet. 2013;106:135-141. How to cite this article: Nieuwenhuis D, Pujol-Gualdo N, Arnoldussen IAC, Kiliaan AJ. Adipokines: A gear shift in puberty. Obesity Reviews. 2020;21:e13005. https://doi.org/ 10.1111/obr.13005 1467789x, 2020, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/obr.13005, Wiley Online Library on [10/03/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are gover
Ions Ions are charged substances that have formed through the gain or loss of electrons. Cations form from the loss of electrons and have a positive charge while anions form through the gain of electrons and have a negative charge. Cation Formation Cations are the positive ions formed by the loss of one or more electrons. The most commonly formed cations of the representative elements are those that involve the loss of all of the valence electrons. Consider the alkali metal sodium (Na) . It has one valence electron in the n=3 energy level. Upon losing that electron, the sodiu ion now has an octet of electrons from the second energy level and a charge of 1+ . The electron arrangement of the sodium ion is now the same as that of the noble gas neon. Consider a similar process with magnesium and aluminum. In this case, the magnesium atom loses its two valence electrons in order to achieve the same arrangement as the noble gas neon and a charge of 2+ . The aluminum atom loses its three valence electrons to have the same electron arrangement as neon and a charge of 3+ . For representative elements under typical conditions, three electrons is usually the maximum number that will be los. Representative elements will not lose electrons beyond their valence because they would have to "break" the octet of the previous energy level which provides stability to the ion. Anions Anions are the negative ions formed from the gain of one or more electrons. When nonmetal atoms gain elections, they often do so until their outermost principal energy level achieves an octet. For fluorine, which has an electron arrangement of (2, 7), it only needs to gain one electron to have the same electron arrangement as neon. Forming an octet (eight electrons in the outer shell) provides stability to the atom. Fluorine will gain one electron and have a charge of 1− . The electron arrangement of the fluoride ion (2, 8) will also change to reflect the gain of an electron. Oxygen has an electron arrangement of (2, 6) and needs to gain two electrons to fill the n=2 energy level and achieve an octet of electrons in the outermost shell. The oxide ion will have a charge of 2− as a result of gaining two electrons. Under typical conditions, three electrons is the maximum that will be gained in the formation of anions. Subatomic Particles in an Ion Since ions form from the gain or loss of electrons, we can also look at the number of subatomic particles (protons, neutrons, and electrons) found in an ion. Remember that the number of protons determines the identity of the element and will not change in a chemical process. Example 2.5.1 How many protons, neutrons, and electrons in a single oxide (O2−) ion? Solution Oxygen has the atomic number 8 so both the atom and the ion will have 8 protons. The average atomic mass of oxygen is 16. Therefore, there will be 8 neutrons (atomic mass−atomic number=neutrons) . A neutral oxygen atom would have 8 electrons. However, the anion has gained two electrons so O2− has 10 electrons. We can also use information about the subatomic particles to determine the identity of an ion. Example 2.5.2 An ion with a 2+ charge has 18 electrons. Determine the identity of the ion. Solution If an ion has a 2+ charge then it must have lost electrons to form the cation. If the ion has 18 electrons and the atom lost 2 to form the ion, then the neutral atom contained 20 electrons. Since it was neutral, it must also have had 20 protons. Therefore the element is calcium. Polyatomic Ions A polyatomic ion is an ion composed of two or more atoms that have a charge as a group (poly = many). The ammonium ion (see figure below) consists of one nitrogen atom and four hydrogen atoms. Together, they comprise a single ion with a 1+ charge and a formula of NH+4 . The hydroxide ion (see figure below) contains one hydrogen atom and one oxygen atom with an overall charge of 1− . The carbonate ion (see figure below) consists of one carbon atom and three oxygen atoms and carries an overall charge of 2− . The formula of the carbonate ion is CO2−3 . The atoms of a polyatomic ion are tightly bonded together and so the entire ion behaves as a single unit. The figures below show several examples. Soult Screenshot 2-2-1.png Figure 2.5.1 : The ammonium ion (NH+4) is a nitrogen atom (blue) bonded to four hydrogen atoms (white). Soult Screenshot 2-2-2.png Figure 2.5.2 : The hydroxide ion (OH−) is an oxygen atom (red) bonded to a hydrogen atom. Soult Screenshot 2-2-3.png Figure 2.5.3 : The carbonate ion (CO2−3) is a carbon atom (black) bonded to three oxygen atoms. The table below lists a number of polyatomic ions by name and by structure. The heading for each column indicates the charge on the polyatomic ions in that group. Note that the vast majority of the ions listed are anions - there are very few polyatomic cations. 1− 2− 3− 1+ Table 2.5.1 : Common Polyatomic Ions acetate, CH3COO− carbonate, CO2−3 arsenate, AsO3−3 ammonium, NH+4 bromate, BrO−3 chromate, CrO2−4 phosphite, PO3−3 chlorate, ClO−3 dichromate, Cr2O2−7 phosphate, PO3−4 chlorite, ClO−2 hydrogen phosphate, HPO2−4 cyanide, CN− oxalate, C2O2−4 dihydrogen phosphate, H2PO−4 peroxide, O2−2 hydrogen carbonate, HCO−3 silicate, SiO2−3 hydrogen sulfate, HSO−4 sulfate, SO2−4 hydrogen sulfide, HS− sulfite, SO2−3 hydroxide, OH− hypochlorite, ClO− nitrate, NO−3 nitrite, NO−2 perchlorate, ClO−4 permanganate, MnO−4 The vast majority of polyatomic ions are anions, many of which end in -ate or -ite. Notice that in some cases such as nitrate (NO−3) and nitrite (NO−2) , there are multiple anions that consist of the same two elements. In these cases, the difference between the ions is the number of oxygen atoms present, while the overall charge is the same. As a class, these are called oxyanions. When there are two oxyanions for a particular element, the one with the greater number of oxygen atoms gets the -ate suffix, while the one with the fewer number of oxygen atoms gets the -ite suffix. The four oxyanions of chlorine are shown below, which also includes the use of the prefixes hypo- and per-. ClO− , hypochlorite ClO−2 , chlorite ClO−3 , chlorate ClO−4 , perchlorate Not your usual ion Soult Screenshot 2-2-4.png "Drink you milk. It's good for your bones." We're told this from early childhood, and with good reason. Milk contains a good supply of calcium, part of the structure of bone. However, there are two other ionic components of hydroxyapatite, the mineral component. Phosphate ion and hydroxide ion make up the remainder of the inorganic material in bone. News You Can Use Bone is a very complex structure. It is composed of protein (mainly collagen), hydroxyapatite (a calcium-phosphate-hydroxide mixture), some other minerals, and contains 10 - 20% water. The calcium/phosphate ratios are not stoichiometric, but vary somewhat from one portion of bone to the next. Bones are very strong but will break under enough stress. Regular exercise and proper nutrition help to increase bone strength. Watch a video about bone structure at http://www.youtube.com/watch?v=d9owEvYdouk Nitrate is an anion with a complex bonding structure. Major sources for this ion in drinking water are runoff from fertilizer, septic tank leakage, sewage, and natural deposits. High concentrations of nitrates represent a significant health hazard, especially to infants. The nitrate in the body is converted to nitrite, which then binds to hemoglobin. This binding decreases the ability of hemoglobin to transport oxygen, thus depriving the cells of the O2 needed for proper functioning. Cyanide production is widespread throughout nature. Forest fires will produce significant amounts of cyanide. Many plants contain cyanide, and it is produced by a number of bacteria, algae, and fungi. Cyanide is used industrially in metal finishing, iron and steel mills, and in organic synthesis processes. This material is also an important component for the refining of precious metals. Formation of a complex between cyanide and gold allows extraction of this metal from a mixture.
LESSON 4. Cellular Respiration • Define cellular respiration • Identify the stages of clan respiration You have just learned how the energy from the sun is captured, processed, and stored in the form of glucose. Cellular respiration, another important life process, is the means by which cells release the stored energy in glucose to make adenosine triphosphate (ATP). The primary goal of this life process is to convert stored energy into usable form, such as ATP, for the cells to carry out their functions. Cellular respiration involves several chemical reactions. The reactions can be summed up in the following equation: C6 H12 O6 + 602 ----- 6 CO₂ +6H₂O + ATP Glucose oxygen carbon dioxide water energy Aerobic respiration reactions, or cellular respiration that takes place in the presence of oxygen, can be grouped into three stages glycolysis, Krebs cycle, and electron transport chain (ETC). Stage 1: Glycolysis Glycolysis is the process that breaks down one molecule of 6-C glucose into 3-C pyruvates or pyruvic acids. It also releases four molecules of ATP. This process occurs in the cytoplasm of the cell. The following is the step-by-step process of glycolysis. Take note that several enzymes are involved in this process. 1. The first step of glycolysis requires energy. It can only proceed when the two ATP molecules donate energy to the glucose by transferring a phosphate group with the help of an enzyme, producing glucose 6-phosphate 2. Then, a specific enzyme promotes the rearrangement of the atoms, producing the fructose 6-phosphate. 3. The action of the enzyme in step 2 promotes the transfer of a phosphate group from another ATP molecule, forming fructose 1,6-bisphosphate. 4. The resulting fructose 1,6-bisphosphate molecules, with the help of another enzyme, splits into two molecules, each with three carbon backbones. These two sugars are dihydroxyacetone phosphate and glyceraldehyde 3-phosphate. 5. Another important enzyme then rapidly interconverts the molecules of dihydro-xyacetone phosphate and glyceraldehyde 3-phosphate. This produces two molecules of glyceraldehyde 3-phosphate or 3-phosphoglyceraldehyde (PGAL) 6. The succeeding step involves another enzyme-mediated action. The hydrogen (H) from PGAL is transferred to the oxidizing agent, nicotinamide adenine dinucleotide (NAD), which forms NADH. A phosphate (P) is also added from the cytosol of the cell to oxidize the two molecules of PGAL, forming two 1.3-bisphosphoglycerate. 7. A phosphate (P) from 1,3-biphosphoglycerate is transferred to ADP to form ATP. This happens for each of the two 1,3-bisphosphoglycerate. resulting to a yield of two ATP and two 3-phosphoglycerate molecules. 8. A phosphate is transferred from 3-phosphoglycerate molecules from the third carbon to the second carbon, forming 2-phosphoglycerate molecules A hydrogen atom and a hydroxyl ((OH) group is released, which then combines to form water (H2O). The removal of H2O from 2-phosphoglycerate results in the formation of 2- phosphoglycerate molecules. 9. A hydrogen atom and a hydroxyl ((OH) group is released, which then combines to form water (H2O). The removal of H2O from 2-phosphoglycerate results in the formation of two phosphoenolpyruvic acid (PEP) 10. Phosphate (P) from PEP is transferred to ADP (and forms ATP) and the final product, pyruvic acid. This reaction yields two molecules of pyruvic acid and two ATP molecules In summary, a single glucose molecule that undergoes the process of glycolysis produces two molecules of pyruvic acid, four molecules of ATP, two molecules of NADEL and two molecules of H.O. However, only two molecules of ATP are counted as net products since two molecules of ATP are spent throughout the process. Stage II: Krebs Cycle The Krebs cycle, named after its proponent Sir Hans Adolf Krebs, is a cyclical series of enzyme-controlled reactions. This stage of cellular respiration occurs in the matrix of the mitochondria. It is sometimes. called the citric acid cycle (CAC) since it produces citric acid. Citric acid contains three carboxyl (COOH) groups; hence, it is also called the tricarboxylic acid cycle (TCA). This requires the pyruvic acids produced during glycolysis. The main function of this cycle is to produce high-energy-yielding molecules, namely, NADH and flavin adenine dinucleotide (FADH) that will later on be used in the electron transport chain reaction. Figure 6-7. Summary of glycolysis and corresponding products in each reaction presented (See Appendix F on page 285 for an enlarged and complete version of the image.) An initial process is needed for the Krebs cycle to begin. As a pyruvate molecule from glycolysis enters the mitochondrion, it undergoes an important preliminary ate to form acetyl-CoA reaction. Coenzyme-A (COA) combines with pyruvate help of an enzymatic complex. This conversion also produces CO, and NADH. The Krebs cycle is summarized as follows. Take note that several enzymes are involved in this process. 1. The Krebs cycle technically begins when the acetyl-CoA combines with oxaloacetic acid (OAA), a 4-C molecule, to produce citric acid, a 6-C molecule. 2. With the aid of an enzyme, the citric acid now goes through a series of reactions that releases energy. Water molecule is removed from the citric acid and is returned in a different location. The-OH group is repositioned, forming the molecule isocitrate. 3. Isocitrate is then oxidized, forming the a-ketoglutarate, a 5-C molecule. The byproducts of this reaction are NADH and CO, 4 The a-ketoglutarate loses its CO, and a coenzyme-A is added in its place. The decarboxylation occurs with the help of NAD, which then becomes NADH. The resulting molecule is called succinyl-CoA. 5. Succinyl-CoA is converted into succinate. Also in this reaction, a molecule of guanosine triphosphate (GTP) is synthesized. The GTP molecule has similar structure and energy properties to that of ATP and is used by cells the same way. The free phosphate group attacks the succinyl-CoA molecule, which detaches the COA. Then, phosphate is attached to GDP to come up with GTP, similar to the process that occur in ATP synthesis (from ADP to ATP). 6. Two hydrogens are removed from succinate, A molecule of flavin adenine dinucleotide (FAD), a coenzyme similar to NAD, is reduced to FADH, as it takes the hydrogens from the succinate. This reaction produces the fumarate. 7. Fumarate is then converted into malate as the addition of a water molecule is catalyzed. The final reaction is the regeneration of oxaloacetate. The resulting byproduct of this regeneration is NADH Recall that two pyruvate molecules were produced during glycolysis, causing the Krebs cycle to turn twice. Each tuts produces three molecules of NADH, single ATH one FADIH, and the by-product CO, which is exhaled. Stage III: Electron Transport Chain The electron transport chain (ETC) is a series of photon pumps on the inner membrane of the mitochondrion. Electron transport is the last stage of the cellular respiration. In this stage, the energy from NADH and FADH, from the Krebs cycle is transferred to ADP to produce ATP. This process is generally known as oxidative phosphorylation. This energy coupling mechanism in the cell was revealed by the work of Peter stored energy in the form of proton (1) gradient to phosphorylate (add phosphate) ADP and produce ATP. The pumping of hydrogen sons across the inner membrane creates higher concentration ions in the inner membrane than on the outside of the membrane. This chemiosmotic gradient causes the ions to flow back across the membrane where the concentration of ions is lower. ATP synthase lined in the matrix serve as a channel protein, helping the ions to move across the membrane. The chemiosmotic gradient powers the phosphorylation of ADP to ATP, which also occurs in the ATP synthase. After passing through the ETC, the oxygen, being the final hydrogen acceptor, combines with two electrons and two protons, forming a water molecule. Water is a by-product of cellular respiration and is excreted. MINI TEST 6-3 1. Which energy-releasing pathway yields the most ATF in each glucose molecule? 2. Briefly describe the two stages of aerobic respiration that follow glycolysis: (a) Krebs cycle (b) Electron transport chain Anaerobic Respiration Most cells carry out arrobic respiration when oxygen is present. Aerobic respiration is an efficient process that yields a lot of ATP. However, many organisms thrive in mud, marshes, animal gut, canned goods, sewage treatment pond, and deep oceans where oxygen is scarce. Organisms that can live without oxygen are called anaerobes. Cellular respiration that proceeds without the presence of oxygen is called anaerobic respiration. In the event that the oxygen supply becomes low, aerobic cells also perform fermentation and lactic acid fermentation anaerobic pathways. There are two common anaerobic pathways in these cells, alcoholic fermentation and lactic acid fermentation. In alcoholic fermentation, ethyl alcohol and carbon dioxide are produced by some cells using the pyruvate from glycolysis. Each pyruvate molecule is rearranged into acetaldehyde and carbon dioxide, which is eventually released. NADII gives up electrons to acetaldehyde to form ethanol Fermentation is widely used in the industry. Yeast, a fungus used in making bread. can undergo anaerobic respiration. Bakers aux sugar, flour, water, and yeast to form the bread dough. The dough rises due to the carbon dioxide and alcohol released by the yeast cells trapped in air bubbles. Beer and wine manufacturers, we yeast to ferment the sugars in wheat and grape juice, forming alcoholic beverages such as beer and wine. In some cells, glycolysis produces two pyruvates, two NADH molecules, and two ATP molecules. Pyruvate itself becomes the final acceptor of the electrons from the NADH that produces the final product: lactate. Oftentimes, this product is called lactic acid. Human skeletal muscles can carry out fermentation when the blood cannot supply the cells with adequate oxygen during strenuous activities. When lactic acid builds up in the muscles, fatigue, burning sensation, and cramps result. Lactic acid will continue to build up until there is adequate supply of oxygen. Lactic acid is then converted back into pyruvate in the liver. Muscles also restore normal functions. Have you ever wondered why milk or cream turns sour after some time? Bacterial cells that undergo fermentation are responsible in producing lactate that turns the milk sour. These bacteria are used in manufacturing yogurt and sour milk products. Fermentation pathways do not breakdown and utilize the glucose completely. ATP is no longer produced beyond the process of glycolysis. Thus, energy produced is just enough for some single-celled organisms, or the energy can only be used by multicellular organisms for a short period.
PHOTOSYNTHESIS LIGHT DEPENDENT REACTION 1. Photosystem II (PSII) – Light Absorption & Water Splitting • Light energy (photons) excites electrons in chlorophyll molecules. • These high-energy electrons leave PSII and are passed into the electron transport chain (ETC). • Meanwhile, water molecules are split (photolysis) into: o O₂ (released as a by-product into the atmosphere) o H⁺ ions (protons, which build up inside the thylakoid) o Electrons (e⁻), which replace the ones lost by PSII. 2. Electron Transport Chain (ETC) • Excited electrons move through protein carriers embedded in the thylakoid membrane. • As they move, their energy pumps H⁺ ions into the thylakoid space, creating a proton gradient (high H⁺ inside, low outside). 3. ATP Production (ATP Synthase) • The buildup of H⁺ ions acts like a “waterfall” of potential energy. • These protons flow back across the membrane through ATP synthase, a protein complex that acts like a turbine. • This flow drives the conversion of ADP + Pi → ATP, which provides energy for the Calvin cycle. 4. Photosystem I (PSI) • Electrons arriving from the ETC enter PSI. • Sunlight excites them again, boosting them to a higher energy level. 5. NADPH Production • The energized electrons are transferred to NADP⁺. • Along with a proton (H⁺), this forms NADPH, another energy carrier. • NADPH is then delivered to the Calvin cycle to help build glucose. End Products of Light-Dependent Reactions: • ATP (energy source for Calvin cycle) • NADPH (reducing power for glucose synthesis) • O₂ (released into the atmosphere as waste) Light-Independent Reactions (Calvin Cycle) • These reactions do not directly require sunlight. • They occur in the stroma of the chloroplast (the fluid-filled space surrounding the thylakoids). • The inputs are ATP and NADPH (from light-dependent reactions) and CO₂ (from the atmosphere). • The outputs are glucose (C₆H₁₂O₆) and other carbohydrates. Think of the Calvin cycle as a factory that uses the energy and “raw materials” made in Stage I (ATP & NADPH) to build sugars. The 3 Main Steps of the Calvin Cycle 1. Carbon Fixation • CO₂ from the atmosphere enters the chloroplast and diffuses into the stroma. • Each CO₂ molecule attaches to a 5-carbon sugar called RuBP (ribulose-1,5-bisphosphate). • This reaction is catalyzed by the enzyme RuBisCO (Ribulose-1,5-bisphosphate carboxylase/oxygenase — the most abundant enzyme on Earth!). • The result is a short-lived 6-carbon compound, which immediately splits into two 3-carbon molecules called 3-PGA (3-phosphoglycerate). Summary: CO₂ + RuBP → 2 × 3-PGA 2. Reduction Phase • The 3-PGA molecules are “energized” and converted into G3P (glyceraldehyde-3-phosphate), a more energy-rich 3-carbon sugar. • This transformation requires: o ATP (provides energy) o NADPH (provides high-energy electrons and hydrogen atoms). • Some of the G3P molecules will eventually be combined to form glucose and other sugars. Summary: 3-PGA + ATP + NADPH → G3P 3. Regeneration of RuBP • Not all G3P molecules leave the cycle. Most of them are used to regenerate RuBP so the cycle can continue. • This regeneration also requires ATP. • For every 3 turns of the cycle, 5 G3P molecules are recycled to regenerate 3 molecules of RuBP. Summary: G3P + ATP → RuBP The Full Cycle Balance • To make one G3P molecule that can exit the cycle (and later form glucose), the cycle must run 3 times, fixing 3 molecules of CO₂. • To make one glucose molecule (C₆H₁₂O₆), the cycle must run 6 times (since glucose needs 6 carbon atoms). Inputs (for 1 glucose): • 6 CO₂ • 18 ATP • 12 NADPH Outputs: • 1 glucose (C₆H₁₂O₆) • 18 ADP + 18 Pi • 12 NADP⁺ Day vs Night Clarification • The Calvin Cycle is called light-independent, but that doesn’t mean it only happens at night. • It usually happens during the day because it depends on ATP and NADPH, which are only produced in light-dependent reactions (when sunlight is available). Simplified Analogy • Carbon fixation = The factory brings in CO₂ as raw material. • Reduction = Workers use energy (ATP & NADPH) to shape the raw material into useful products (G3P). • Regeneration = Some products are recycled to keep the factory running (RuBP is re-formed). • Output = After enough cycles, the factory produces glucose, the “food” of the plant.
Make mcq quiz with 4 option in which one is correct -'10 Basis of Material Science • .....;;;";;;"~~;;,,;;,,,,;.;.,,;;,,,;,,;.;,.,------------ 6. Temporary materials: Some materials are meant to be placed in the oral cavity for a short period of time for different reasons. • Temporary crowns: While a permanent crown is prepared in the dental laboratory, the patient must wait for few days before it can be fabricated and cemented into place. Does patient experience any problems during this time period? If the tooth is vital (the pulp is alive), the patient is likely to experience pain and sensitivity while eating and drinking, also it looks unesthetic. What can be done to solve this problem? A temporary crown is placed before the patient leaves the clinic. It is constructed and luted in the same appointment in which the crown preparation is done. Temporary crowns are not very strong or esthetic but they serve adequately till the permanent crown is ready to be cemented. • Temporary restorations: Sometimes it is difficult to decide immediately the best line of treatment for a particular tooth. The exact condition of the pulp may not be obvious to the dentist from the patient's symptoms. A dentist removes all or part of the decay and then places a temporary restoration to have time to observe the behaviour of the pulp or to give the pilip time to heal before deciding the further treatment required. Classification based on Location of Fabrication 4,9 Materials can be classified based on the location of fabrication into: • Direct restorative materials. • Indirect restorative materials Direct restorative materials: They include those materials which are used to restore cavity preparations directly in the oral cavity (Box 1.5). Box 1.5: Examples of direct restorative materials Amalgam, composites, glass ionomer and other materials, which set by chemical reactions in the mouth. Indirect restorative materials: It includes those restorations which must be fabricated outside the mouth, indirectly on a cast/ model/ die, because their processing condition would harm oral tissues. Materials used in the construction of such prosthesis are called indirect restorative materials (Box 1.6). Box 1.6: Examples of indirect restorative materials Gold inlays, crowns of metal, ceramic and polymers, which are processed at elevated temperatures. Some indirect composite restorations can be processed under specific wavelength of light, e.g. Ceramage. Classification based on Longevity of Use 1. Permanent restorations: These restorations are not planned to be replaced for a particular time period. Though they are referred to as permanent, actually they are not, e.g. fillings, crowns, bridges and dentures do not last forever (Fig. 1.5). 2. Temporary restorations: These restorations are planned to be replaced in a short period of time, such as few days to weeks. For ~ Permanent C/) c c -.2 0 c- :;::; Cll co Interim ~ Q; 0 .8ll::1iJ C/) o~ Cll a:: c:=:J Temporary Time period Fig. 1.5: Diagram depicting the time period of use of a restoration. (Arrow in permanent restoration depicts that such restorations are not planned to be replaced for a long period of time.) Introducton to Dental Materials Dental materials Box 1.7: Characteristics of metals 1. High thermal and electrical conductivity 2. Ductility (pure metals are very soft and they can be bent without breaking) 3. Opacity (they do not transmit light) 4. Luster (they have a surface that strongly reflects light and appears bright and shiny) 5. They tend to dissolve to some extent in water or other aqueous solutions, producing cations. 6. All metals are white (actually gray) except for gold, which is yellow, and copper, which is reddish. 7. All metals are solid at room temperature except mercury, which is liquid at room temperature and is used with silver alloys as amalgam. 8. All metals have high melting temperatures because of high strength of the metallic bond that holds the atoms together. 3. Polymers 4. Composites Composites are mixtures of two or more of the first three classes in which the different components remain distinct from one another in the final structure. A common example is composite resin. Fig. 1.7a: Three-dimensional structure of iron (metal) Metals Metals are the oldest of the three classes of materials that have been used as dental materials. Metals are characterized by metallic bonds (Box 1.7) which will be discussed in the next chapter. Metals solidify with their atoms in a regular or crystalline arrangement (see Chapter 2), often in the form of a cube (Fig. 1.7a). example, temporary fillings done in a tooth during root canal treatment, which have to be replaced within 2-4 days during subsequent visits. They are used to protect the tooth and provide function till the final restoration is done. 3. Interim restoration: At times, dental treatment requires "long-term" definite temporary restorations or "interim" restorations. For examle, a 7-year-old child, met with trauma and fractured one of his central incisors. A large composite build- up may serve his immediate requirement until the root formation is completed and a permanent crown is placed. 5 Classification based on the Chemical Nature of the Material These are the atoms that make up a material and the way they are bonded together determine the properties of that materiaLS Weak bonds make for weak materials and vice versa (Table 1.4). Materials can be classified into different categories based on their primary atomic bonds (Fig. 1.6): 1. Metals 2. Ceramics Fig. 1.6: Classification of dental materials based on chemical nature 12 Basis of Material Science Box 1.9: Benefits of ceramics in dentistry 1. Many ceramic oxides are used as pigmenting agents. These oxides produce good range of colors. Due to this characteristic, we are able to match almost any tooth color with good esthetic results. 2. They are inert, i.e. not chemically reactive. This quality provides ceramics with good bio- compatibility. 3. Ceramic materials are translucent, like natural teeth. This translucency gives the ceramic crown a more natural appearance than any other dental material. Fig. 1.7b: Internal arrangement of tetrahedral structure of ceramic (silica) four large oxygen atoms surround smaller silicon atom Ceramics A ceramic is a compound formed by the union of a metallic and a non-metallic element (Box 1.8). Most of these materials are oxides, formed by the union of oxygen with metals such as silicon, aluminum, calcium and magnesium (Fig.1.7b). Ceramics may be simple or complex. Examples of simple ceramics are alumina and silica. Examples of complex ceramics are feldspar (potassium aluminum silicate) and kaolin (hydrated aluminum silicate). Ceramics may be crystalline or non- crystalline (i.e. amorphous). Porcelain is a specific type of ceramic used extensively in dentistry (Box 1.9). Box 1.8: Characteristics of ceramics 1. High melting points. 2. Brittleness, which means they cannot be bent or deformed (no sliding) to any extent without actually cracking and breaking. 3. They are poor conductor of heat and electricity. 4. They are chemically inert. 5. They have excellent esthetic result in terms of matching natural teeth. Fig. 1.8: Stucture of synthetic polymer Polymers They are the latest addition (early to mid- 1900s) to dental materials. Most of the polymers are nowadays synthesized by humans. Polymers are giant, long-chain organic molecules (Fig. 1.8). Polymers are characterized by covalent bonds within each molecule, giving them tremendous strength in a single direction. Try to break a nylon rope by pulling it! They are poor conductors of heat and electri- city. Most polymers have a structure containing thousands of carbon atoms linked together like beads on a string. Others, such as silicone polymers are formed with silicon-oxygen bonds. Introducton to Dental Materials Table 1.4: Characteristics of different materials 13 Characteristics Bond Properties Crystal structure Metals Metallic bonding High strength and hardness, high electrical and thermal conductivity BCC, FCC, or HCP unit cells Ceramics Ionic or covalent bonding, or both High hardness and stiffness, electrically insulating, refractory, and chemically inert Crystalline or amorphous Polymers Covalent bonding Low sensitivity, high electrical resistivity, and low thermal conductivity, strength and stiffness vary widely Amorphous and crystalline Composites Composites are combinations of any of the basic ceramic, metallic and polymeric materials (Box 1.10). Each material that makes up composites is called a phase. Their properties tend to be somewhere between those of their basic constituents and are used to enhance their performance, longevity and handling chracterstics. Box 1.10: Types of composites in dentistry 1. Ceramic - metallic composite: Tungsten carbide bur. 2. Metal - polymer composite: Die materials in dental laboratory. 3. Ceramic - polymer composite: Enamel, dentin, bone and restorative composites. A composite is a kind of "combination" of materials, which compliment each other. The properties lacking in one material are compensated by those of the other material. For example, restorative composite has two phases, namely resin and fillers. Teeth and bones are examples of natural composites. Enamel is a composite of hydroxyapatite (which is a ceramic material) and protein (which is a polymer). EVALUATION OF DENTAL MATERIALS Most manufacturers of dental materials maintain a quality assurance programme (As per international standard like ADA specifications) and materials are thoroughly tested before being released into the market for dental practitioner (Fig. 1.9). Laboratory Evaluations Most ADA/ ANSI specifications involve laboratory tests. The tests performed as per these specifications are useful but they all are performed in vitro, (carried out in the laboratory away from the clinical conditions) which have a lot of limitations in clinical practice.lO Clinical Notes 1. For example, most of the direct restorative materials are tested for their compressive strength but ultimately the material is subjected to a combination of compressive, tensile and shear stresses, which may decide the final success or failure of the material under masticatory load. 2. Similarly upper dentures mostly fracture along the midline because of bending. Hence a bending or transverse strength ~B-a-s-is-o-f-M-a-t-e-ria-I-S~c-ie-n-c-e-------------- ---------. test is far more meaningful for denture base materials than a compression test. Clinical Trials The majority of new materials are subjected to extensive clinical trials normally in co-operation with a dental college or hospital departments prior to their release. CONCLUSION As the number of available materials is going up, it is important that the dentist remains more aware about new products so that their judgement about the selection of material remains successful. Materials which have not been thoroughly evaluated should be avoided, specially with clinical dentistry falling under Consumer Protection Act (CPA). I Research and development I iI Manufacturer/analysis Ideal requirements for clinical use: Thermal, optical, mechanical, chemical, biological Available materials and their properties are evaluated Launch of new I product Choice and selection of material by the dentist Critical assessment based on clinical performance I I H feedback to I
The cytoskeleton is a network of thin tubes and filaments that crisscrosses the cytosol. The tubes and filaments give shape to the cell from the inside in the same way that tent poles support the shape of a tent. The cytoskeleton also acts as a system of internal tracks, shown in Figure 4-18, on which items move around inside the cell. The cytoskeleton’s functions are based on several struc- tural elements. Three of these are microtubules, microfilaments, and intermediate filaments, shown and described in Table 4-2. Microtubules Microtubules are hollow tubes made of a protein called tubulin. Each tubulin molecule consists of two slightly different subunits. Microtubules radiate outward from a central point called the centrosome near the nucleus. Microtubules hold organelles in place, maintain a cell’s shape, and act as tracks that guide organelles and molecules as they move within the cell. Microfilaments Finer than microtubules, microfilaments are long threads of the beadlike protein actin and are linked end to end and wrapped around each other like two strands of a rope. Microfilaments con- tribute to cell movement, including the crawling of white blood cells and the contraction of muscle cells. Intermediate Filaments Intermediate filaments are rods that anchor the nucleus and some other organelles to their places in the cell. They maintain the inter- nal shape of the nucleus. Hair-follicle cells produce large quantities of intermediate filament proteins. These proteins make up most of the hair shaft. 84 CHAPTER 4 TABLE 4-2 The Structure of the Cytoskeleton Property Microtubules Microfilaments Intermediate filaments Structure hollow tubes made of two strands of intertwined protein fibers coiled into coiled protein protein cables Protein subunits tubulin, with two subunits: å actin one of several types of and ∫ tubulin fibrous proteins Main function maintenance of cell shape; cell maintenance and changing of maintenance of cell shape; motility (in cilia and flagella); cell shape; muscle contraction; anchor nucleus and other chromosome movement; movement of cytoplasm; cell organelles; maintenance of organelle movement motility; cell division shape of nucleus Shape Microtubules provide a path for organelles and molecules as they move throughout the cell. FIGURE 4-18 Microtubules Nucleus Endoplasmic reticulum Mitochondrion Ribosomes Copyright © by Holt, Rinehart and Winston. All rights reserved. Copyright © by Holt, Rinehart and Winston. All rights reserved. CELL STRUCTURE AND FUNCTION 85 1. Explain how the fluid mosaic model describes the plasma membrane. 2. List three cellular functions that occur in the nucleus. 3. Describe the organelles that are found in a eukaryotic cell. 4. Identify two characteristics that make mitochon- dria different from other organelles. 5. Contrast three types of cytoskeletal fibers. CRITICAL THINKING 6. Relating Concepts If a cell has a high energy requirement, would you expect the cell to have many mitochondria or few mitochondria? Why? 7. Analyzing Information How do scientists think that mitochondria originated? Why? 8. Analyzing Statements It is not completely accurate to say that organelles are floating freely in the cytosol. Why not? SECTION 3 REVIEW During cell division, centrioles organize microtubules that pull the chromosomes (orange) apart. The centrioles are at the center of rays of microtubules, which have been stained green with a fluorescent dye. FIGURE 4-20 Cilia and Flagella Cilia (SIL-ee-uh) and flagella (fluh-JEL-uh) are hairlike structures that extend from the surface of the cell, where they assist in movement. Cilia are short and are present in large numbers on certain cells, whereas flagella are longer and are far less numerous on the cells where they occur. Cilia and flagella have a membrane on their outer surface and an internal structure of nine pairs of micro- tubules around two central tubules, as Figure 4-19 shows. Cilia on cells in the inner ear vibrate and help detect sound. Cilia cover the surfaces of many protists and “row” the protists through water like thousands of oars. On other protists, cilia sweep water and food particles into a mouthlike opening. Many kinds of protists use flagella to propel themselves, as do human sperm cells. Centrioles Centrioles consist of two short cylinders of microtubules at right angles to each other and are situated in the cytoplasm near the nuclear envelope. Centrioles occur in animal cells, where they organize the microtubules of the cytoskeleton during cell division, as shown in Figure 4-20. Plant cells lack centrioles. Basal bodies have the same structure that centrioles do. Basal bodies are found at the base of cilia and flagella and appear to organize the devel- opment of cilia and flagella.