MBB317. Dr D MANGNALL OBESITY. Lecture 2
|
|
- Wilfrid Palmer
- 6 years ago
- Views:
Transcription
1 MBB317 Dr D MANGNALL OBESITY Lecture 2 When the structure of the insulin receptor was first discovered it was assumed that the active beta subunit tyrosine kinase would phosphorylate some intracellular protein substrate, and a lot of time and energy was spent looking for intracellular substrates, and it took several years before any were clearly identified. To my knowledge there are only a few such substrates known so far. These are known as IRS1, IRS2 and IRS3, etc, where IRS means insulin receptor substrate. Part of insulin s actions depend on the phosphorylation of these intracellular substrates, although what happens after that is not totally clear. However, that is only part of the insulin action story. The receptor itself autophosphorylates, that is the receptor phosphorylates itself on tyrosine residues within the beta subunit. This phosphorylated form of the receptor is then recognised by other proteins within the cell, which then dock onto it, and form a complex, and these complexes are part of the signalling pathway. The key features as far as these lectures are concerned are that the receptor becomes active as a tyrosine kinase when insulin binds, and in the test tube the activated receptor will phosphorylate artificial proteins made as a polymer of glutamate and tyrosine. Thus, in vitro one can incubate the receptor with the glutamate: tyrosine polymer, and 32 P labelled ATP, and in the presence of insulin the activated tyrosine kinase will transfer 32 P from the ATP to tyrosine residues in the artificial acceptor protein, and this forms the basis of an assay to determine the ability of insulin to switch on the kinase, and to initiate the insulin signalling pathway. The other way of measuring the ability of insulin to switch on the tyrosine kinase activity is to incubate the receptors with 32 P- ATP as before, but to leave out the artificial tyrosine: glutamate polymer, so that the receptor itself becomes radioactively labelled with 32 P on tyrosine residues, and to measure the amount of labelling on the receptor. Both assay systems have been used successfully. The next overhead shows the insulin binding and insulin induced tyrosine kinase activity of receptors isolated from human muscle using the assay system, which looks at autophosphorylation of the receptor.
2 Figure 8 muscle. Insulin binding and autophosphorylation of receptors from human The panel on the left shows the binding of I labelled insulin. Here receptors have been incubated with a fixed amount of I 125 -labelled insulin and increasing amounts of non-labelled insulin. Results from receptors from lean controls are shown in the open symbols, and the filled symbols show data from receptors prepared from obese subjects. There is no difference in the ability of either group of receptors to bind insulin, thus the alteration in the insulin sensitivity is not due to any change in ability of the alpha subunits to form the binding domain for the insulin, and the insulin binds equally well to both sets of receptors. The right hand panel shows the ability of insulin to induce receptor autophosphorylation. The top line (with open symbols ) is the response for receptors from non-obese control subjects, and the bottom 3 sets are from 3 preparations of receptors from obese subjects. The asterisks indicate that the upper values are significantly higher than those of the lower group, and suggest that receptors from muscle obese subjects are inherently defective in their ability to autophosphorylate, and since this is part of the way in which insulin signalling is initiated, suggests that muscle from obese subjects is relatively insulin resistant. The next overhead shows similar data, but from mice rather than humans. Figure 9. Autophosphorylation of receptors from mouse muscle.
3 This again shows that receptors from obese mice are insulin resistant relative to receptors from lean controls. The next overhead (Figure 10) shows that with receptors from adipocytes (rather than muscle ), the situation seems to be reversed, ie, the ability of receptors from obese animals to phosphorylate a glutamate: tyrosine artificial acceptor protein is greater than that of receptors from lean controls. Figure 10. Phosphorylation of poly Glut:Tyr by receptors from rat adipocytes.
4 Collectively, this sort of data suggests that at least part of the reason for the altered insulin sensitivities of tissues in obese humans and rodents can be attributed to alterations at the level of the insulin receptor, and suggests that for obese subjects, insulin signalling via receptor auto phosphorylation is reduced in the muscle, but that signalling via the phosphorylation of intracellular proteins is enhanced in the adipose tissue. It should be clear from these kinds of studies that the obese human and the obese rodent are metabolically different from their lean, non-obese counterparts. There are lots of studies of this kind in the literature, and conflicting reports are not unknown, so the story is not one which is yet set in stone. However, one can construct a story around this kind of data which is consistent at least with the notion that in the obese situation skeletal muscle becomes less insulin sensitive, and adipose tissue changes in its insulin sensitivities. Thus the capacity for insulin stimulated oxidation of glucose to CO2 is reduced in adipose tissue in the obese, whilst the insulin stimulated uptake for 2-deoxyglucose is only slightly affected, and in the absence of insulin the basal level of 2 deoxyglucose uptake is increased. In skeletal muscle insulin binding is unaffected, but insulin signalling, at least via receptor autophosphorylation is reduced, In adipose tissue insulin signalling, as measured by the ability of insulin to stimulate the receptor to phosphorylate an artificial protein substrate, is increased., but not all insulin sensitive functions are stimulated (glucose oxidation to CO2 is clearly reduced ), but none the less some insulin signalling mechanism is potentially at least increased. This may be related to increased lipoprotein lipase activity, and together with the decreased capacity for
5 glucose oxidation, may indicate an increase in the ability of the adipose tissue to synthesise and store fatty acids as triglyceride. An unanswered question is 'how is altered kinase activity of the receptor achieved?' This is unclear at present, but it may be that alternative splicing of the receptor gene exons leads to alterations in receptor activity. Whist these kinds of study highlight metabolic differences between the obese and non-obese individuals they don't really say too much about why the obese subject has all that extra adipose tissue. So one can ask what accounts for the large amount of adipose tissue? ie what do we know about control of adipose tissue growth? ADIPOSE TISSUE GROWTH AND DEVELOPMENT. Although there have been considerable advances in recent years in understanding how adipocytes are formed, particularly an explosive increase in the identification of transcription factors which promote adipogenesis, there remain major gaps in our knowledge and only a speculative understanding of how it may relate to the obese state. (At present the work seems to be at the stage of establishing the general principles of adipogenesis rather than at the level of saying how this relates to the development of obesity.) The salient features of what is currently known are highlighted in the box below and subsequently discussed a little more fully.
6 ADIPOSE TISSUE DEVELOPMENT In both rodents and humans, adipose tissue develops during late gestation and first few weeks after birth. Adipose tissue comprises a mixture of cell types Precursor cells called preadipocytes fibroblast-like little of the enzymatic make up of the mature adipocyte can divide Mature Adipocytes Are fully differentiated do not divide Mild obesity results from existing adipocytes enlarging Severe obesity involves an increase in the number of adipocytes as well Much of our understanding of the differentiation process comes from studies of cells in culture eg 3T3-L1 ) 3T3-F442A ) from embryonic tissue Ob17 from adult tissue when treated in culture with a cocktail of stimulants these cells form fully differentiated adipocytes ( 3T3 lines need camp dexamethasone and insulin, Ob17 needs fatty acids ) generally a mixture of insulin, T3, glucocorticoids, GH, prostaglandins have been used. Transformation occurs in a step wise fashion in which a number of transcription factors are activated sequentially. The main ones are PPARγ and δ ( Peroxisome Proliferator-Activated Receptor ) C/EBP ( CCAAT/ Enhancer Binding Protein ) ADD-1 (Adipocyte Determination and Differentiation factor-1) In both rodents and humans adipose tissue development occurs during late gestation and the first few weeks after birth. It is now clear that adipocytes arise from a population of pre-adipocyte stem cells, which are lipid-free mesenchymal cells, which, in contrast to the mature adipocyte, are fibroblast-like and have little of the enzymatic capacity that characterises the mature adipocyte. The preadipocytes are able to divide and increase in numbers whilst the mature, fully differentiated adipocyte does not divide. The adipose tissue
7 thus comprises a mixture of cell types, but it is the presence of the preadipocytes that explains why the adipose tissue can increase in mass. In humans, mild obesity results from the enlargement of the adipocyte that accompanies increased triglyceride accumulation, whilst severe obesity involves an increase in the number of adipocytes as well. In rodents, and probably in humans also, high fat and high carbohydrate diets lead to increases in adipose tissue mass involving the appearance of new fat cells. This occurs firstly by the pre-adipocytes proliferating, which occurs within days, followed by a terminal differentiation step which takes weeks during which time there is lipid deposition within the adipocytes. Much of our current understanding of the molecular events of the differentiation process comes from studies of cell cultures. Some of the lines are derived from embryonic tissue (eg. 3T3-L1 and 3T3-F442A cells) and some from adult animals (eg the Ob17 cell line ). When these cells are treated in culture with a cocktail of stimulants they will convert from pre-adipocytes to the fully differentiated adipocyte, a process that involves the very ordered activation of a whole range of genes. The stimulants needed vary depending on the cell line ( perhaps reflecting the stage of development of the animal from which they were first isolated) so that the 3T3 cell lines respond to mixture of high cyclic AMP, dexamethasone and insulin, whist Ob17 cells will differentiate on expose to high fatty acid levels. Generally some combination of hormones ( insulin, triiodothyronine, glucocorticoids and growth hormone ) and prostaglandins has been used to promote the in vitro conversion of the preadipocytes in culture to the mature adipocyte. This transformation occurs in stepwise, sequential fashion, and involves the sequential activation of a number of transcription factors, the predominant ones being PPARγ and δ ( Peroxisome Proliferator-Activated Receptor ), the C/EBP (CCAAT/Enhancer Binding Protein ) family members and ADD-1 ( Adipocyte Differentiation and Determination factor-1). The PPAR proteins are found on the nuclear membrane, and when complexed to the appropriate ligand will act as transcription factors by moving into the nucleus and interacting with promoter regions of genes and switching on these genes specifically. PPARγ exists in 2 forms, PPARγ1 and PPARγ2 formed by alternative splicing. PPARγ2 is expressed at high levels in adipose tissue, whilst PPARγ1 is found at low levels in many other tissues. PPARγ2 is induced early in the adipocyte differentiation and appears to be a crucial regulator of many fat-specific genes as well as a 'master
8 regulator' capable of triggering the whole of the differentiation program. Interestingly, the adipogenic activity of PPARγ is markedly enhanced by insulin. PPARγ is not the only transcription factor of importance in adipocyte differentiation. C/EBPα,β and δ are all markedly increased relatively late in the process of adipogenesis, at least in cells in culture. However, in C/EBPα knockout mice, although there is a major reduction in the amount of fat in the adipose tissue, fat cell differentiation still occurs. The available evidence suggests that C/EBPα and PPARγ cooperate dramatically in vivo, and when expressed together the differentiation inducing effect is markedly stimulated. The promoter region for PPARγ 2 contains 2 C/EBP binding regions, and C/EBPβ, which is increased early in adipogenesis, increases the expression of PPARγ. Another factor, which interacts with PPARγ is ADD-1. Under conditions, which are not conducive to adipogenesis, this transcription factor induces 2 key enzymes of fatty acid metabolism, fatty acid synthetase and lipoprotein lipase, without stimulating fat cell differentiation, but under conditions, which favour adipogenesis ADD-1 increases the number of cells undergoing differentiation. This is at least in part due to an increase in the activity of PPARγ, ADD-1 is also involved in the control of key genes involved in cholesterol metabolism. A simplified scheme is shown in Figure 11 below. (Fig 1from Grimaldi review). FACTORS INFLUENCING PREADIPOCYTE TO ADIPOCYTE DIFFERENTIATION Insulin ADD-1 Long Chain Fatty acids Prostaglandin I2 Glucocorticoids camp, LIF, GH PPARδ C/EBPβ C/EBPδ PPARγ C/EBPα Terminal Differentiation Related Genes DIFFERENTIATING PREADIPOCYTE ADIPOCYTE ADIPOCYTE (From Grimaldi PA. The roles of PPARs in adipocyte differentiation (2001). Prpgress in Lipid Research ) Exposure of the pre-adipocytes to glucocorticoids, camp, growth hormone (GH) and leukaemia inhibitory factor (LIF) promotes the activation of C/EBPδ and C/EBPβ. In the presence of long chain fatty acid and prostaglandin I2 this leads to the activation of PPARδ. These changes occur at the point that the cultures reach confluence and
9 result in the cells becoming committed to differentiation. An early marker enzyme activity appearing at this stage is lipoprotein lipase. The second stage is a proliferation stage during which there is a clonal expansion of these committed cells, which divide and multiply. During this stage the pattern of activated transcription factors changes. C/EBPαbecomes the predominant C/EBP form, and is induced by the action of the β and δ forms. C/EBPα, β and δ also combine with PPARδ to activate PPARγ. If the necessary hormones and PPARγ ligands are available, the transcriptional activity of PPARγ activates the gene cascade that leads to adipogenesis. Activation of PPARγ is also promoted by ADD-1, which is activated by the presence of insulin. The appearance of PPARγ and C/EBPα leads to a terminal differentiation stage associated with the expression of a number of adipose tissue specific genes. ADD-1 is needed for the expression of the fatty acid synthetase, and ADD-1 expressing cells produce lipid molecules that bind to and activate PPARγ. Thus, late on in the process, PPARγ activates C/EBPα expression and PPARγ and C/EBPα co-operation brings about maximal differentiation and full lipogenic capacity. Almost certainly this scheme of things will be shown to be much more complex as more research is done. There are several issues which are clearly yet to be resolved, not least of which is the nature of the PPARγ ligand, and which are the important hormones. Despite these recent advances in understanding how adipogenesis and differentiation are achieved at the molecular level, there is very little hard data currently available which relates directly to how this process is accelerated or exaggerated in the obese subject. However, one may speculate that the ingestion, digestion and absorption of nutrients, which is generally believed to increase during the time at which obesity develops, gives rise not only to nutrients which might stimulate insulin release from the pancreas, but also produces a range of signals in the form of hormones from the gut, and signals from the brain. These gut signals may be part of the hormonal environment which promotes adipogenesis. Insulin is known to enhance the adipogenic activity of PPARγ, possibly through a change in phosphorylation state of PPARγ. The abundance of PPARγ falls in starvation and in diabetes. The insulin stimulation of PPARγ may be due to an increase in C/EBPβ and C/EBPδ which are induced by insulin in cells in culture. ADD1/SREBP1 activity is also increased by insulin. Glucocorticoids are also important in this scheme, since induction of PPARγ by C/EBPβ and C/EBPδ. is dependent upon the presence of a glucocorticoid.
10 Although precisely how this relates to the development of an obese state remains to be elucidated, THE OBESITY GENE AND LEPTIN Regulation of adipose tissue mass Since total body mass can be kept constant (+/- 1% over the course of many years) despite a widely fluctuating food intake and energy expenditure, it has been postulated that there must be a powerful, slow, feedback pathway operating. It has been proposed that it is the total amount of fat which is sensed. It is postulated that when mammals overeat the resultant extra fat signals to the brain that the body is obese and the animal then responds to signals from the brain by eating less and/or burning more fuel. The key points, (derived mainly from animal studies, but probably applying to mammals generally) are: a). The hypothalamus, ( more specifically the ventromedial nucleus of the hypothalamus, VMN ) is probably the main control centre for satiety and energy expenditure. Damage can result in obesity, similar to that in ob/ob mice, whilst stimulation reduces eating and increases energy expenditure. b). Rats forced to overeat lay down excess fat, but when offered a normal eating routine they eat less until a normal body weight Is obtained. c). Surgical removal of substantial amounts of fat is followed by increased eating and an increase in the remaining fat stores. (Presumably this has implications for surgical interventionist approaches such as 'apronectomy' or liposuction ). d). Overfeeding one of a pair of parabiotic mice, (ie. mice joined surgically to have some interchange of blood) causes reduced food intake and loss of weight in the partner mouse, suggesting transfer of a circulating hormone. e). Hypothalamic lesions on one of a pair of parabiotic mice leads to obesity in that mouse, but reduced food intake and loss of adipose tissue in the other mouse, again suggesting transfer of a proposed satiety hormone from the obese mouse to the lean mouse. Ie. the 'fed' signal is produced by both mice but not recognised by the mouse with the hypothalamic lesion, and the normal mouse gets an overdose of the 'stop eating ' signal.
11 f). If an ob/ob mouse is parabiotically joined to a normal mouse it eats less and looses weight. This suggests the obesity of the ob/ob mouse is due the loss of a satiety hormone, which is then provided by the normal animal of the parabiotic pair. g). Mice homozygous for another mutation, db (diabetes), are also obese. The db/db phenotype reflects a defect in the action of the Ob protein (leptin) due to a defect in the receptor for leptin. Normal mice parabiotically joined to db/db mice reject food and die of starvation. When ob/ob mice are joined to db/db mice the ob/ob mouse reduces food intake and looses adipose tissue. The ob/ob mouse appears to react to a putative excess of normal Ob protein produced by the db/db partner. All of this suggests that fat produces a factor, which acts as a satiety factor, and that when normal animals overeat the resultant extra fat somehow signals to the brain that the body is obese, with the result that less food is consumed and/ or energy expenditure is increased. In 1994 J.M. Friedman and colleagues reported the cloning of a gene from ob/ob mice ( the ob gene ), which had been recognised 40 years earlier to lead to profound obesity and type ll diabetes in mice homozygous for the mutation, resulting in a state resembling morbid obesity in man. The ob gene was only expressed to any extent by adipose tissue The gene consists of 3 exons and 2 introns, and encodes a 4.5 kilobase mrna derived from coding sequences in exons 2 and 3. The predicted protein product, which is now called Leptin, ( from the Greek Leptos, meaning 'thin' ), was derived from a 167 amino acid open reading frame which included a 21 amino acid secretory signal sequence, suggesting that the product was a secreted protein. They suggested mice homozygous for ob gene fail to secrete the normal protein, and that leptin may represent a 'satiety' factor. It is now recognised that the original strain of ob/ob mice used by Friedman's group had a non-sense mutation at codon 105, and so produced a mutated form of leptin. The protein is now known to be 84 % homologous to the human protein, and similar proteins have now been described for several other mammals, chickens and eels ( but not fruit flies!). In 1995, it was shown that injections of purified leptin caused mice to lose weight and maintain their weight loss.
12 Mice lost 40% of their body weight after a month of daily injections. Compared to pair fed untreated obese mice, the injected group lost 50% more weight than the untreated group, suggesting reduced food intake alone cannot explain the weight loss. Leptin also had an effect on energy expenditure, sluggish ob/ob mice became more active, and their slow metabolism was stimulated, thermogenesis was stimulated. Similar results were obtained using a strain of mouse, which, like the human, becomes obese when its diet contains too much fat, a condition called dietary induced obesity.. These mice, like the ob/ob mice, ate less of the high fat food and lost weight in response to injections of the Ob protein. In mice, which stay lean, when young but become fat as they get older, also lost weight when injected with the Ob protein. Thus, this kind of obesity (not due to a mutation in the ob gene) is correctable by the Ob protein. Ob also causes weight loss in mice that are not fat. Lean mice receiving a relatively high dose of Ob lost 12% of body weight and virtually all body fat after 4 days of injections and maintained the new weight for a further 2 weeks whilst they continued to receive injections. End of Lecture 2
BIOL212 Biochemistry of Disease. Metabolic Disorders - Obesity
BIOL212 Biochemistry of Disease Metabolic Disorders - Obesity Obesity Approx. 23% of adults are obese in the U.K. The number of obese children has tripled in 20 years. 10% of six year olds are obese, rising
More informationObesity in aging: Hormonal contribution
Obesity in aging: Hormonal contribution Hormonal issues in obesity and aging Hormonal role in regulation of energy balance Genetic component in hormonal regulation Life style contribution to hormonal changes
More information18. PANCREATIC FUNCTION AND METABOLISM. Pancreatic secretions ISLETS OF LANGERHANS. Insulin
18. PANCREATIC FUNCTION AND METABOLISM ISLETS OF LANGERHANS Some pancreatic functions have already been discussed in the digestion section. In this one, the emphasis will be placed on the endocrine function
More informationIn The Name Of God. In The Name Of. EMRI Modeling Group
In The Name Of God In The Name Of God EMRI Modeling Group Cells work together in functionally related groups called tissues Types of tissues: Epithelial lining and covering Connective support Muscle movement
More informationHomeostasis and Mechanisms of Weight Regulation
Homeostasis and Mechanisms of Weight Regulation Purpose In this activity students will investigate how negative feedback mechanisms function to maintain homeostatic balance using a recently discovered
More informationHormones. Prof. Dr. Volker Haucke Institut für Chemie-Biochemie Takustrasse 6
Hormones Prof. Dr. Volker Haucke Institut für Chemie-Biochemie Takustrasse 6 Tel. 030-8385-6920 (Sekret.) 030-8385-6922 (direkt) e-mail: vhaucke@chemie.fu-berlin.de http://userpage.chemie.fu-berlin.de/biochemie/aghaucke/teaching.html
More informationLeptin Intro/Signaling. ATeamP: Angelo, Anthony, Charlie, Gabby, Joseph
Leptin Intro/Signaling ATeamP: Angelo, Anthony, Charlie, Gabby, Joseph Overview Intro to Leptin Definition & Sources Physiology Bound vs. Free Receptors Signaling JAK/STAT MAPK PI3K ACC Experimental findings
More informationab Adipogenesis Assay Kit (Cell-Based)
ab133102 Adipogenesis Assay Kit (Cell-Based) Instructions for Use For the study of induction and inhibition of adipogenesis in adherent cells. This product is for research use only and is not intended
More informationKEY CONCEPT QUESTIONS IN SIGNAL TRANSDUCTION
Signal Transduction - Part 2 Key Concepts - Receptor tyrosine kinases control cell metabolism and proliferation Growth factor signaling through Ras Mutated cell signaling genes in cancer cells are called
More informationInsulin Resistance. Biol 405 Molecular Medicine
Insulin Resistance Biol 405 Molecular Medicine Insulin resistance: a subnormal biological response to insulin. Defects of either insulin secretion or insulin action can cause diabetes mellitus. Insulin-dependent
More informationLeptin part 2. Mary ET Boyle
Leptin part 2 Mary ET Boyle Leptin Feedback: leptin levels drop during starvation, when fat depots are depleted to support the organism s basic energy needs, leptin levels rise during refeeding where fat
More informationPEPCK. The Regulation of Eukaryotic Gene Expression. Why choose PEPCK? PEPCK. PEPCK overexpression in muscle. The Supermouse.
PEPK The Regulation of Eukaryotic Gene Expression..using the example of PEPK This is an acronym for an enzyme PhosphoEnol Pyruvate arboxykinase This enzyme is NLY regulated by gene expression! No allosteric
More informationENERGY FROM INGESTED NUTREINTS MAY BE USED IMMEDIATELY OR STORED
QUIZ/TEST REVIEW NOTES SECTION 1 SHORT TERM METABOLISM [METABOLISM] Learning Objectives: Identify primary energy stores of the body Differentiate the metabolic processes of the fed and fasted states Explain
More informationBEIGE AND BROWN FAT: BASIC BIOLOGY AND NOVEL THERAPEUTICS Dr. Carl Ascoli
BEIGE AND BROWN FAT: BASIC BIOLOGY AND NOVEL THERAPEUTICS Dr. Carl Ascoli Symposium Co-Chairs: Bruce M. Spiegelman (Harvard/Dana Farber) and Sven Enerbäck (U.Gothenburg) April 17-23, 2015 Snowbird Resort,
More informationGENERAL CHARACTERISTICS OF THE ENDOCRINE SYSTEM FIGURE 17.1
GENERAL CHARACTERISTICS OF THE ENDOCRINE SYSTEM FIGURE 17.1 1. The endocrine system consists of glands that secrete chemical signals, called hormones, into the blood. In addition, other organs and cells
More informationHORMONES AND CELL SIGNALLING
HORMONES AND CELL SIGNALLING TYPES OF CELL JUNCTIONS CHEMICAL SIGNALS AND MODES OF ACTION Endocrine system produces chemical messages = hormones that are transported from endocrine gland to target cell
More informationChapter 12. Ingestive Behavior
Chapter 12 Ingestive Behavior Drinking a. fluid compartments b. osmometric thirst c. volumetric thirst Eating a. energy sources b. starting a meal c. stopping a meal d. eating disordersd Drinking a. fluid
More information5.0 HORMONAL CONTROL OF CARBOHYDRATE METABOLISM
5.0 HORMONAL CONTROL OF CARBOHYDRATE METABOLISM Introduction: Variety of hormones and other molecules regulate the carbohydrates metabolism. Some of these have already been cited in previous sections.
More informationProject Summary. Funded by The Beef Checkoff. Regulation of Marbling Development in Beef Cattle by Specific Fatty Acids
Project Summary Regulation of Marbling Development in Beef Cattle by Specific Fatty Acids Principal Investigators: S. Smith 1, B. Johnson 2 and M. Doumit 3 Texas A&M University 1, Texas Tech University
More informationInsulin mrna to Protein Kit
Insulin mrna to Protein Kit A 3DMD Paper BioInformatics and Mini-Toober Folding Activity Student Handout www.3dmoleculardesigns.com Insulin mrna to Protein Kit Contents Becoming Familiar with the Data...
More informationReceptors Functions and Signal Transduction- L4- L5
Receptors Functions and Signal Transduction- L4- L5 Faisal I. Mohammed, MD, PhD University of Jordan 1 PKC Phosphorylates many substrates, can activate kinase pathway, gene regulation PLC- signaling pathway
More informationMetabolism of cardiac muscle. Dr. Mamoun Ahram Cardiovascular system, 2013
Metabolism of cardiac muscle Dr. Mamoun Ahram Cardiovascular system, 2013 References This lecture Mark s Basic Medical Biochemistry, 4 th ed., p. 890-891 Hand-out Why is this topic important? Heart failure
More informationNUTRITION & MALIGNANCY: An Overview
NUTRITION & MALIGNANCY: An Overview UNIVERSITY OF PNG SCHOOL OF MEDICINE AND HEALTH SCIENCES DISCIPLINE OF BIOCHEMISTRY & MOLECULAR BIOLOGY PBL MBBS II SEMINAR VJ Temple 1 Malignancy and Weight loss (Cachexia)
More informationUNIVERSITY OF PNG SCHOOL OF MEDICINE AND HEALTH SCIENCES DIVISION OF BASIC MEDICAL SCIENCES DISCIPLINE OF BIOCHEMISTRY AND MOLECULAR BIOLOGY
1 UNIVERSITY OF PNG SCHOOL OF MEDICINE AND HEALTH SCIENCES DIVISION OF BASIC MEDICAL SCIENCES DISCIPLINE OF BIOCHEMISTRY AND MOLECULAR BIOLOGY GLUCOSE HOMEOSTASIS An Overview WHAT IS HOMEOSTASIS? Homeostasis
More information(*) (*) Ingestion, digestion, absorption, and elimination. Uptake of nutrients by body cells (intestine)
Human Digestive System Food is pushed along the digestive tract by peristalsis the rhythmic waves of contraction of smooth muscles in the wall of the canal Accessory glands. Main stages of food processing
More informationThe molecule that serves as the major source of readily available body fuel is: a. fat. b. glucose. c. acetyl CoA. d. cellulose.
The molecule that serves as the major source of readily available body fuel is: a. fat. b. glucose. c. acetyl CoA. d. cellulose. Dietary fats are important because: a. they keep blood pressure normal.
More informationAyman Mesleh & Leen Alnemrawi. Bayan Abusheikha. Faisal
24 Ayman Mesleh & Leen Alnemrawi Bayan Abusheikha Faisal We were talking last time about receptors for lipid soluble hormones.the general mechanism of receptors for lipid soluble hormones: 1. Receptors
More informationType 1 Diabetes 2/23/2015. Endocrine System Hormones. Living with Type 1 Diabetes
Endocrine System Hormones 2007-2008 Living with Type 1 Diabetes Type 1 Diabetes results from the autoimmune destruction of the insulin- producing beta-cells in the pancreas. The lack of insulin leads to
More informationOverall Energy metabolism: Integration and Regulation
Overall Energy metabolism: Integration and Regulation We have discussed various fuels which are oxidized via different catabolic pathways to generate ATP, or reducing equivalents required to carry out
More informationG-Protein Signaling. Introduction to intracellular signaling. Dr. SARRAY Sameh, Ph.D
G-Protein Signaling Introduction to intracellular signaling Dr. SARRAY Sameh, Ph.D Cell signaling Cells communicate via extracellular signaling molecules (Hormones, growth factors and neurotransmitters
More informationChromium is a transition metal element, which belongs to Group VI of the. periodic table (Expert Group on Vitamins and Minerals (EVM), 2002) and
1.0 Introduction 1.1 What is Chromium? Chromium is a transition metal element, which belongs to Group VI of the periodic table (Expert Group on Vitamins and Minerals (EVM), 2002) and commonly exists in
More informationLESSON 3.3 WORKBOOK. How do we decide when and how much to eat?
Appetite The psychological desire to eat, driven by feelings of pleasure from the brain. Hunger The biological or physiological need to eat, caused by a release of hormones from the digestive tract. LESSON
More informationFinal Review Sessions. 3/16 (FRI) 126 Wellman (4-6 6 pm) 3/19 (MON) 1309 Surge 3 (4-6 6 pm) Office Hours
Final Review Sessions 3/16 (FRI) 126 Wellman (4-6 6 pm) 3/19 (MON) 1309 Surge 3 (4-6 6 pm) Office ours 3/14 (WED) 9:30 11:30 am (Rebecca) 3/16 (FRI) 9-11 am (Abel) Final ESSENTIALS Posted Lecture 20 ormonal
More informationCHM333 LECTURE 34: 11/30 12/2/09 FALL 2009 Professor Christine Hrycyna
Lipid Metabolism β-oxidation FA Acetyl-CoA Triacylglycerols (TAGs) and glycogen are the two major forms of stored energy in vertebrates Glycogen can supply ATP for muscle contraction for less than an hour
More informationPropagation of the Signal
OpenStax-CNX module: m44452 1 Propagation of the Signal OpenStax College This work is produced by OpenStax-CNX and licensed under the Creative Commons Attribution License 3.0 By the end of this section,
More informationLecture 5: Cell Metabolism. Biology 219 Dr. Adam Ross
Lecture 5: Cell Metabolism Biology 219 Dr. Adam Ross Cellular Respiration Set of reactions that take place during the conversion of nutrients into ATP Intricate regulatory relationship between several
More informationLipid Metabolism. Remember fats?? Triacylglycerols - major form of energy storage in animals
Remember fats?? Triacylglycerols - major form of energy storage in animals Your energy reserves: ~0.5% carbs (glycogen + glucose) ~15% protein (muscle, last resort) ~85% fat Why use fat for energy? 1 gram
More informationWeek 3 The Pancreas: Pancreatic ph buffering:
Week 3 The Pancreas: A gland with both endocrine (secretion of substances into the bloodstream) & exocrine (secretion of substances to the outside of the body or another surface within the body) functions
More informationPrinciples of Anatomy and Physiology
Principles of Anatomy and Physiology 14 th Edition CHAPTER 25 Metabolism and Nutrition Metabolic Reactions Metabolism refers to all of the chemical reactions taking place in the body. Reactions that break
More informationWEIGHT GAIN DURING MENOPAUSE EMERGING RESEARCH
MENOPAUSE WHEN DOES IT OCCUR? The cessation of the menstrual cycle for one year. WEIGHT GAIN DURING MENOPAUSE EMERGING RESEARCH Jan Schroeder, Ph.D. Chair of The Department of Kinesiology California State
More informationIntegration Of Metabolism
Integration Of Metabolism Metabolism Consist of Highly Interconnected Pathways The basic strategy of catabolic metabolism is to form ATP, NADPH, and building blocks for biosyntheses. 1. ATP is the universal
More informationEB Education Revision Guide. How to work with Homeostasis: Part 2 Blood Glucose Regulation
EB Education Revision Guide How to work with Homeostasis: Part 2 Blood Glucose Regulation Blood Glucose Regulation a) Why your body regulates glucose levels What you need to know about Homeostasis: Part
More informationDigestion: Endocrinology of Appetite
Digestion: Endocrinology of Dr. Ritamarie Loscalzo Medical Disclaimer: The information in this presentation is not intended to replace a one on one relationship with a qualified health care professional
More informationMarch 19 th Batool Aqel
March 19 th - 2013 6 Batool Aqel Hormones That Bind to Nuclear Receptor Proteins Hormones bind to their receptors.whether the receptor is found in the nucleus or the cytoplasm, at the end they are translocated
More informationEAT TO LIVE: THE ROLE OF THE PANCREAS. Felicia V. Nowak, M.D., Ph.D. Ohio University COM 22 January, 2008
EAT TO LIVE: THE ROLE OF THE PANCREAS Felicia V. Nowak, M.D., Ph.D. Ohio University COM 22 January, 2008 THE ROLE OF THE PANCREAS Exocrine pancreas Endocrine pancreas THE ROLE OF THE PANCREAS EXOCRINE
More informationEndocrine System Hormones. AP Biology
Endocrine System Hormones 2007-2008 Regulation Why are hormones needed? u chemical messages from one body part to another u communication needed to coordinate whole body u daily homeostasis & regulation
More informationCARBOHYDRATE METABOLISM 1
CARBOHYDRATE METABOLISM 1 web 2017 József Mandl Strategy of metabolism 1 Strategy of metabolism to extract energy ( hydrogen ) from the environment to store the energy excess to store hydrogen CH 3 O 2
More informationnumber Done by Corrected by Doctor
number 20 Done by Corrected by Rana Ghassan Doctor Only 4 questions in the mid-term exam are based on the 4 lectures to be given by Dr Faisal. Dr Faisal will give us 10 lectures, the first 4 are included
More information2013 W. H. Freeman and Company. 12 Signal Transduction
2013 W. H. Freeman and Company 12 Signal Transduction CHAPTER 12 Signal Transduction Key topics: General features of signal transduction Structure and function of G protein coupled receptors Structure
More informationCell Communication and Cell Signaling
Cell Communication and Cell Signaling Why is cell signaling important? Why is cell signaling important? Allows cells to communicate and coordinate functions/activities of the organism Usually involves
More informationANSC/NUTR 601 GENERAL ANIMAL NUTRITION Stearoyl-CoA desaturase, VLDL metabolism, and obesity
ANSC/NUTR 601 GENERAL ANIMAL NUTRITION Stearoyl-CoA desaturase, VLDL metabolism, and obesity I. Stearoyl coenzyme A desaturase and obesity in rodents A. Stearoyl coenzyme A desaturase (SCD) is the 9 desaturase.
More informationWhat systems are involved in homeostatic regulation (give an example)?
1 UNIVERSITY OF PNG SCHOOL OF MEDICINE AND HEALTH SCIENCES DIVISION OF BASIC MEDICAL SCIENCES DISCIPLINE OF BIOCHEMISTRY AND MOLECULAR BIOLOGY GLUCOSE HOMEOSTASIS (Diabetes Mellitus Part 1): An Overview
More informationMamofillin New aesthetic perspective
New aesthetic perspective info@ White adipose tissue (WAT) White adipose tissue (WAT) is the prevalent type in human adults functioning as the major storage site for the lipids absorbed from daily intake
More informationINTRODUCTION TO THE BIOCHEMISTRY OF HORMONES AND THEIR RECPTORS
INTRODUCTION TO THE BIOCHEMISTRY OF HORMONES AND THEIR RECPTORS 1 Introduction to the Biochemistry of Hormones and their Receptors Lectuctre1 Sunday 17/2/ Objectives: 1. To understand the biochemical nature
More informationBiochemistry: A Short Course
Tymoczko Berg Stryer Biochemistry: A Short Course Second Edition CHAPTER 27 Fatty Acid Degradation Dietary Lipid (Triacylglycerol) Metabolism - In the small intestine, fat particles are coated with bile
More informationREAD THESE INSTRUCTIONS!
READ THESE INSTRUCTIONS! A. Please write your name at the top of this page, and on the Scantron sheet; fill in your student ID on the Scantron form. B. Make sure you fill in the exam letter (under your
More informationComprehensive and Easy Course Notes for BIOL1040 Exams and Assessment
Comprehensive and Easy Course Notes for BIOL1040 Exams and Assessment MODULE 1: PRINCIPLES OF CELL FUNCTION Membrane Structure & Function Cellular membranes are fluid mosaics of lipids and proteins Phospholipids
More informationBi156 lecture 2, 1/6/12. Eating and weight regulation
Bi156 lecture 2, 1/6/12 Eating and weight regulation Introduction: weight regulation in an affluent society In our society much effort and money is expended on regulation of weight. Failure to maintain
More informationEndocrine System Hormones (Ch. 45)
Endocrine System Hormones (Ch. 45) Regulation Why are hormones needed? chemical messages from one body part to another communication needed to coordinate whole body daily homeostasis & regulation of large
More informationHormonal Regulations Of Glucose Metabolism & DM
Hormonal Regulations Of Glucose Metabolism & DM What Hormones Regulate Metabolism? What Hormones Regulate Metabolism? Insulin Glucagon Thyroid hormones Cortisol Epinephrine Most regulation occurs in order
More informationRole of fatty acids in the development of insulin resistance and type 2 diabetes mellitus
Emerging Science Role of fatty acids in the development of insulin resistance and type 2 diabetes mellitus George Wolf Insulin resistance is defined as the reduced responsiveness to normal circulating
More informationOxidation of Long Chain Fatty Acids
Oxidation of Long Chain Fatty Acids Dr NC Bird Oxidation of long chain fatty acids is the primary source of energy supply in man and animals. Hibernating animals utilise fat stores to maintain body heat,
More informationEligibility The NCSF online quizzes are open to any currently certified fitness professional, 18 years or older.
Eligibility The NCSF online quizzes are open to any currently certified fitness professional, 18 years or older. Deadlines Course completion deadlines correspond with the NCSF Certified Professionals certification
More informationMotivation 1 of 6. during the prandial state when the blood is filled
Motivation 1 of 6 I. INTRODUCTION A. Motivation: a condition (usually internal) that initiates, activates, or maintains goal-directed behavior. B. Archery analogy 1. undrawn bow has no potential energy
More informationAN ANIMAL S DIET MUST SUPPLY CHEMICAL ENERGY, ORGANIC MOLECULES, AND ESSENTIAL NUTRIENTS
1 ANIMAL NUTRITION 2 3 4 5 6 7 Food is taken in, taken apart, and taken up in the process of animal nutrition In general, animals fall into three categories: Herbivores eat mainly plants and algae Carnivores
More informationChapter 4 Reading Guide
Chapter 4 Reading Guide 1. How many covalent bonds does carbon (C) form? 2. What is the chemical formula for glucose? 3. List the major dietary monosaccharides and disaccharides. What are the components
More informationPathogenesis of Diabetes Mellitus
Pathogenesis of Diabetes Mellitus Young-Bum Kim, Ph.D. Associate Professor of Medicine Harvard Medical School Definition of Diabetes Mellitus a group of metabolic diseases characterized by hyperglycemia
More informationLecture 36. Key Concepts. Overview of lipid metabolism. Reactions of fatty acid oxidation. Energy yield from fatty acid oxidation
Lecture 36 Lipid Metabolism 1 Fatty Acid Oxidation Ketone Bodies Key Concepts Overview of lipid metabolism Reactions of fatty acid oxidation Energy yield from fatty acid oxidation Formation of ketone bodies
More informationHistory of Investigation
Acini - Pancreatic juice (1º) (2º) Secretions- neuronal and hormonal mechanisms 1) Secretin - bicarbonate rich 2) Cholecystokinin - enzyme rich Islets of Langerhans (contain 4 cell types) Alpha cells (α)-
More informationCell Quality Control. Peter Takizawa Department of Cell Biology
Cell Quality Control Peter Takizawa Department of Cell Biology Cellular quality control reduces production of defective proteins. Cells have many quality control systems to ensure that cell does not build
More informationUniversità degli Studi di Ferrara
Università degli Studi di Ferrara DOTTORATO DI RICERCA IN FARMACOLOGIA E ONCOLOGIA MOLECOLARE CICLO XXI COORDINATORE Prof. Pier Andrea Borea High Glucose Induces Adipogenic Differentiation of Muscle-Derived
More informationAMPK. Tomáš Kučera.
AMPK (AMP- ACTIVATED PROTEIN KINASE ) Tomáš Kučera tomas.kucera@lfmotol.cuni.cz Department of Medical Chemistry and Clinical Biochemistry 2nd Faculty of Medicine, Charles University in Prague and Motol
More informationGrowth Hormone, Somatostatin, and Prolactin 1 & 2 Mohammed Y. Kalimi, Ph.D.
Growth Hormone, Somatostatin, and Prolactin 1 & 2 Mohammed Y. Kalimi, Ph.D. I. Growth Hormone (somatotropin): Growth hormone (GH) is a 191 amino acid single chain polypeptide (MW 22,000 daltons). Growth
More informationHormones and Homeostasis
Hormones and Homeostasis The endocrine system is a system of organs that releases chemical message molecules, called hormones, into the blood. Unlike the nervous system whose action helps the body react
More informationHormonal regulation of. Physiology Department Medical School, University of Sumatera Utara
Hormonal regulation of nutrient metabolism Physiology Department Medical School, University of Sumatera Utara Homeostasis & Controls Successful compensation Homeostasis reestablished Failure to compensate
More informationMetabolic Syndrome. DOPE amines COGS 163
Metabolic Syndrome DOPE amines COGS 163 Overview - M etabolic Syndrome - General definition and criteria - Importance of diagnosis - Glucose Homeostasis - Type 2 Diabetes Mellitus - Insulin Resistance
More information1Why lipids cannot be transported in blood alone? 2How we transport Fatty acids and steroid hormones?
1Why lipids cannot be transported in blood alone? 2How we transport Fatty acids and steroid hormones? 3How are dietary lipids transported? 4How lipids synthesized in the liver are transported? 5 Lipoprotien
More informationAMPK. Tomáš Kuc era. Ústav lékar ské chemie a klinické biochemie 2. lékar ská fakulta, Univerzita Karlova v Praze
AMPK (AMP- ACTIVATED PROTEIN KINASE ) Tomáš Kuc era Ústav lékar ské chemie a klinické biochemie 2. lékar ská fakulta, Univerzita Karlova v Praze 2013 AMPK AMP-ACTIVATED PROTEIN KINASE present in all eukaryotic
More informationThe Endocrine Pancreas
Chapter 7 The Endocrine Pancreas The pancreas houses two distinctly different tissues. The bulk of its mass is exocrine tissue and associated ducts, which produce an alkaline fluid loaded with digestive
More informationPlasma membranes. Plasmodesmata between plant cells. Gap junctions between animal cells Cell junctions. Cell-cell recognition
Cell Communication Cell Signaling Cell-to-cell communication is essential for multicellular organisms Communicate by chemical messengers Animal and plant cells have cell junctions that directly connect
More informationThe Cell Cycle M G2 G1 G0 S 1
The Cell Cycle M G2 G1 G0 S 1 Cell Cycle G1 (Gap 1) 3 to 12 hours in length Respond to cues from the environment External cues Growth factors that signal the cell to stay in G1 or continue to through the
More informationCompanion to Biosynthesis of Ketones & Cholesterols, Regulation of Lipid Metabolism Lecture Notes
Companion to Biosynthesis of Ketones & Cholesterols, Regulation of Lipid Metabolism Lecture Notes The major site of acetoacetate and 3-hydorxybutyrate production is in the liver. 3-hydorxybutyrate is the
More informationDNA and Protein Synthesis Practice
Biology 12 DNA and Protein Synthesis Practice Name: 1. DNA is often called the "code of life". Actually it contains the code for a) the sequence of amino acids in a protein b) the sequence of base pairs
More informationThe number of microorganisms residing in our intestines is 10 times the number of our somatic and germ cells.
The number of microorganisms residing in our intestines is 10 times the number of our somatic and germ cells. The number of microorganisms residing in our intestines is 10 times the number of our somatic
More informationTHE GLUCOSE-FATTY ACID-KETONE BODY CYCLE Role of ketone bodies as respiratory substrates and metabolic signals
Br. J. Anaesth. (1981), 53, 131 THE GLUCOSE-FATTY ACID-KETONE BODY CYCLE Role of ketone bodies as respiratory substrates and metabolic signals J. C. STANLEY In this paper, the glucose-fatty acid cycle
More information7.06 Cell Biology EXAM #3 April 24, 2003
7.06 Spring 2003 Exam 3 Name 1 of 8 7.06 Cell Biology EXAM #3 April 24, 2003 This is an open book exam, and you are allowed access to books and notes. Please write your answers to the questions in the
More informationGoals and Challenges of Communication. Communication and Signal Transduction. How Do Cells Communicate?
Goals and Challenges of Communication Reaching (only) the correct recipient(s) Imparting correct information Timeliness Causing the desired effect Effective termination Communication and Signal Transduction
More informationWeek 3, Lecture 5a. Pathophysiology of Diabetes. Simin Liu, MD, ScD
Week 3, Lecture 5a Pathophysiology of Diabetes Simin Liu, MD, ScD General Model of Peptide Hormone Action Hormone Plasma Membrane Activated Nucleus Cellular Trafficking Enzymes Inhibited Receptor Effector
More informationEndocrine Disrupters as Obesogens
Endocrine Disrupters as Obesogens Is the environment making us fat? Bruce Blumberg, Ph.D. Department of Developmental and Cell Biology Department of Pharmaceutical Sciences Developmental Biology Center
More informationHORMONES (Biomedical Importance)
hormones HORMONES (Biomedical Importance) Hormones are the chemical messengers of the body. They are defined as organic substances secreted into blood stream to control the metabolic and biological activities.
More informationFAT. It s Not All That! A Closer Look at the Two Main Types of Fat in Our Bodies: Visceral and Subcutaneous Fat
Mary-Kate Perrone Capstone Seminar July 14, 2007 Draft #2 Fat Stats FAT. It s Not All That! A Closer Look at the Two Main Types of Fat in Our Bodies: Visceral and Subcutaneous Fat According to the 2003-2004
More informationChapter 11. Cell Communication. Signal Transduction Pathways
Chapter 11 Cell Communication Signal Transduction Pathways Signal-Transduction Pathway Signal on a cell s surface is converted into a specific cellular response Local signaling (short distance) - Paracrine
More informationBIOH111. o Cell Module o Tissue Module o Skeletal system o Muscle system o Nervous system o Endocrine system o Integumentary system
BIOH111 o Cell Module o Tissue Module o Skeletal system o Muscle system o Nervous system o Endocrine system o Integumentary system Endeavour College of Natural Health endeavour.edu.au 1 Textbook and required/recommended
More informationLESSON 2.2 WORKBOOK. Metabolism: Glucose is the middleman for ATP
DEFINITIONS OF TERMS Homeostasis The tendency toward a relatively stable equilibrium that is maintained by physiological processes. For a complete list of defined terms, see the Glossary. LESSON 2.2 WORKBOOK
More informationLESSON 2.4 WORKBOOK. Part two: Glucose homeostasis in the blood Un-Storing energy
DEFINITIONS OF TERMS Fasting A state of abstinence from all food or drinks that provide calories. For a complete list of defined terms, see the Glossary. LESSON 2.4 WORKBOOK Part two: Glucose homeostasis
More informationIntracellular signalling pathways activated by leptin by Gema FRUHBECK. Presentation by Amnesiacs Anonymous
Intracellular signalling pathways activated by leptin by Gema FRUHBECK Presentation by Amnesiacs Anonymous Introduction to Leptin By Ahrial Young Why is Leptin important? Pleiotropic = it controls the
More informationSupplementary Fig. 1 eif6 +/- mice show a reduction in white adipose tissue, blood lipids and normal glycogen synthesis. The cohort of the original
Supplementary Fig. 1 eif6 +/- mice show a reduction in white adipose tissue, blood lipids and normal glycogen synthesis. The cohort of the original phenotypic screening was n=40. For specific tests, the
More information7.06 Spring of PROBLEM SET #6
7.6 Spring 23 1 of 6 7.6 PROBLEM SET #6 1. You are studying a mouse model of hypercholesterolemia, a disease characterized by high levels of cholesterol in the blood. In normal cells, LDL particles in
More informationEndocrine Notes Mrs. Laux AP Biology I. Endocrine System consists of endocrine glands (ductless), cells, tissues secrete hormones
I. Endocrine System consists of endocrine glands (ductless), cells, tissues secrete hormones regulates metabolism, fluid balance, growth, reproduction A. Hormones 1. chemical signals-cell to cell communication
More informationCopyright Strengthworks International Publishing. All rights are reserved. Updated egor 2: GUIDE
Copyright 2017. Strengthworks International Publishing. All rights are reserved. Updated 02.14.17 THE V-TAPER SOLUTION SUPPLEMENT GUIDE Category 2 Primary Goal Fat Loss Based on your current measurements
More information