Nutrition, Metabolism & Energy Balance I PDF

Nutrition, Metabolism & Energy Balance I Chapter 24 p. 932 – 961 (Sections 24.1 – 24.7) http://2012books.lardbucket.org/books/an-introduction-to- nutrition/section_14/162d91c78c4bfdaeade6c0c77d0b9ee5.jpg...

Nutrition, Metabolism & Energy Balance I Chapter 24 p. 932 – 961 (Sections 24.1 – 24.7) http://2012books.lardbucket.org/books/an-introduction-to- nutrition/section_14/162d91c78c4bfdaeade6c0c77d0b9ee5.jpg 1 Université d’Ottawa | University of Ottawa Disclosure You may only access and use this PowerPoint presentation for educational purposes. You may not post this presentation or the associated vieos online or distribute it without the permission of the author. uottawa.ca 2 Objectives I 2.1 Review the metabolic pathways and their interactions 2.2 Define the absorptive state and justify the key role of insulin in its metabolic regulation 2.3 Define the post absorptive state and describe the roles of glucagon and other supporting mechanisms in the maintenance of blood glucose levels 3  Nutrition o the study of nutrients in food o how the body extracts and uses nutrients o the relationship between diet, health and disease. 4  Nutrients Nutrient: substance in food needed for growth, maintenance, & repair o used for metabolic fuel o some are for cell structures and molecular synthesis ▪ Macronutrients: three major nutrients that make up the bulk of ingested food ▪ Carbohydrates ▪ Lipids ▪ Proteins ▪ Micronutrients: two other nutrients that are required, but only in small amounts ▪ Vitamins ▪ Minerals o Water is required, so technically is a nutrient: 60% by volume of the food we eat 5  Essential vs Non-Essential nutrients Essential (indispensable) nutrients - cannot be synthesized in the body or are synthesized in insufficient amounts so they must be provided by the diet for growth, health and survival throughout life o 40 - 50 nutrients are considered essential – inadequate intake of any essential nutrient leads to a characteristic deficiency disease, that may ultimately lead to death eg iron deficiency anemia Nonessential (dispensable) nutrients – may be eliminated from the diet with no adverse health effects because they are synthesized in the body – Cells (especially liver cells) have ability to convert one type of molecule to another; interconversions allow us to adjust to varying food intakes Energy value of nutrients measured in kilocalories (kcal) – One kca is amount of heat needed to raise temperature of 1 k g of H2O by 1oC 1 kcal = one calorie (C) Carbohydrates and proteins have 4 kcal/g, but lipids have almost 9 kcal/g 6  Health Canada Food Guide Eat a variety of healthy foods each day guidelines represented as portions on a dinner plate Food groups represented – Fruits – Vegetables – Grains – Protein – Dairy Basic dietary principles: eat only what you need (eat less overall); eat plenty of fruits, vegetables, and whole grains; avoid junk food https://food- guide.canada.ca/themes/custom/wxtsub_boot strap/images/food_guide_visual_en.png 7  Carbohydrates Dietary sources Primarily from plants, such as starch (complex CHO) in grains and vegetables Sugars in fruits, sugarcane, sugar beets & honey http://www.weightlossforall.com/wp- content/uploads/2010/08/shutterstock_56950423- 300x200.jpg Small amount in milk sugar, glycogen in meats Insoluble fiber: cellulose in vegetables provides roughage Soluble fiber: pectin in apples and citrus fruits reduces blood cholesterol levels Uses in body Glucose: fuel most used by cells to make ATP ▪ Some cells use fat for energy ▪ Neurons and RBCs rely entirely on glucose Neurons die quickly without glucose Excess glucose is converted to glycogen or fat, then stored Fructose and galactose are converted to glucose by liver before entering circulation Dietary requirements – Recommended daily intake is 45–65% of total calories – Should consist mostly of complex carbohydrates (whole grains & vegetables) 8  LIPIDS ▪ a family of chemical compounds soluble in organic solvents/insoluble in H2O ▪ Contains more stored energy than any other organic compounds. ▪ Almost entirely C and H with almost no O2 Dietary sources – Triglycerides (neutral fats): most abundant form. Found as: ▪ saturated fats in meat, dairy, some tropical plants (coconut) ▪ unsaturated fats found in seeds, nuts, olive oil, and most vegetable oils ▪ trans fats in hydrogenated oils (e.g., margarine and shortening) https://www.cfs.gov.hk/english/multimedia/multimedia_pub/images/multimedia_pub_fsf_158/fs f_158_2.png – Cholesterol found in egg yolk, meats, organ meats, shellfish, and milk products ▪ Liver makes ~85% cholesterol 9  LIPIDS Liver can convert some fatty acids into others – Two essential fatty acids it cannot synthesize: ▪ Linoleic acid – an omega-6 fatty acid (component of lecithin) ▪ Linolenic acid – an omega-3 fatty acid ▪ Both can be found in most vegetable oils Uses in body – Adipose tissue offers protection, insulation, fuel storage – Phospholipids essential in myelin sheaths and all cell membranes – Cholesterol stabilizes membranes; precursor of bile salts, steroid hormones – Prostaglandins → smooth muscle contraction, BP control, inflammation – Major fuel of hepatocytes and skeletal muscle – Help absorb fat-soluble vitamins Dietary requirements – Fats should represent 20–35% of total caloric intake Limit saturated fats to 10% or less of total fat intake Cholesterol can be synthesized to meet needs (not required in diet) 10  Proteins ▪ 3D coiled up chain of amino acids (aa) arranged in a precise sequence ▪ One of the main constituents of our bodies ▪ The greatest amount in muscle tissue ▪ Crucial for regulation and maintenance of processes in our body Dietary sources ▪ Animal products (eggs, milk, fish, most meats), as well as soybeans, are considered complete proteins. Why? ▪ Legumes, nuts, and cereals contain incomplete proteins ▪ Legumes & cereal grains together contain all essential amino acids ▪ 20 AAs, 9 essential must be provided with food ▪ Essential used to make nonessential AAs (if those are not provided with a diet) e.g. our body can convert Phe to Tyr o The requirement for the essential aa much higher in children than in adults!!!! 11  Proteins Uses in the body ▪ Structural materials e.g.: keratin (skin), collagen & elastin (connective tissue) & muscle proteins ▪ Functional molecules e.g.: enzymes and some hormones Three factors help determine whether amino acids in cells are used to synthesize proteins or burned as fuel: 1. All-or-none rule 2. Adequacy of caloric intake 3. Hormonal controls – Anabolic hormones (GH, sex hormones) promote protein synthesis & growth – Adrenal glucocorticoids (released during stress) promote protein breakdown & conversion of amino acids → glucose 12  Nitrogen Balance Homeostatic state where rate of protein synthesis equals rate of breakdown and loss the difference between the total nitrogen consumed and the amount excreted in urine and feces. Positive nitrogen balance: synthesis exceeds breakdown – Normal in growing children, pregnant women, tissue repair Negative nitrogen balance: breakdown for energy exceeds synthesis – Occurs during stress, burns, infection, injury, low quality or quantity of dietary proteins, starvation https://o.quizlet.com/CO96E3eg5QF9fbxdGxMf.g.jpg Dietary requirements – Needed to supply essential amino acids (and make nonessential ones) – Amount needed depends on age, size, metabolic rate, current nitrogen balance ▪ Rule of thumb: daily intake of 0.8 g per kg body weight 13  Vitamins & Minerals Vitamins ▪ Organic compounds that are crucial in helping body use macronutrients ▪ Most function as coenzymes (e.g., B vitamins act as coenzymes when glucose is used to make ATP) ▪ Most must be ingested, except: – Vitamin D (made in skin) – Some B and K synthesized by intestinal bacteria – Beta-carotene (e.g., from carrots) converted in body to vitamin A o No one food group contains all vitamins ▪ Two types of vitamins based on solubility – Water-soluble vitamins o B complex and C are absorbed with water o B12 absorption requires intrinsic factor – Fat-soluble vitamins o A, D, E, and K are absorbed with lipid digestion products o Stored in body, except for vitamin K – Excessive consumption can cause health problems 14  Vitamins & Minerals Vitamins Free radicals (molecules with unpaired electron) generated during normal metabolism – Vitamins A, C, E, and mineral selenium are antioxidants—participants in antioxidant reactions that neutralize dangerous free radicals Good sources of A and C : broccoli, cabbage, cauliflower, brussels sprouts are all good sources of vitamins A and C Megadoses of vitamins not beneficial, and may cause serious health problems (especially fat-soluble vitamins) http://www.baby-kids-parents.com/images/2016-2/Antioxidantfoods.jpg 15  Vitamins & Minerals Minerals ▪ Seven are required in moderate amounts: ▪ Ca2+, P, K+, S, Na+, Cl- & Mg2+ ▪ Others are required in trace amounts ▪ Work with nutrients to ensure proper body functioning ▪ Uptake and excretion are balanced to prevent toxic overload Like vitamins, work with nutrients for proper body functioning – Incorporating minerals into structures makes them stronger ▪ Ca2+, P, and Mg salts harden teeth and strengthen bone – Most ionized in body fluids or bound to organic compounds to form phospholipids, hormones, and various proteins ▪ Iron is essential part of oxygen-binding heme of hemoglobin ▪ Sodium and chloride are major electrolytes in blood ▪ Iodine is necessary for thyroid hormone synthesis 16  https://cdn1.byjus.com/wp-content/uploads/2018/02/ENERGY-AND-HUMAN-LIFE-2.png METABOLISM 17  Metabolism Metabolism: sum of all biochemical reactions in the body, which involve nutrients – Substances are constantly built up (anabolism) and broken down (catabolism) – Even at rest, body uses lots of energy for essential activities (like breathing and absorbing nutrients from food) Anabolism: reactions that build larger molecules or structures from smaller ones; – E.g., synthesis of proteins from amino acids Catabolism: reactions that break down more complex structures to simpler ones – E.g., hydrolysis of proteins into amino acids https://cdn1.byjus.com/wp-content/uploads/2018/02/ATP-min-1.png 18  Three Stages of Metabolism of Energy-Containing Nutrients Cellular Respiration 19  Metabolism Cellular Respiration catabolic breakdown of food fuels where energy from food is captured to form ATP in cells – Goal: to trap chemical energy in ATP which directly powers chemical reactions in cells Energy can also be stored in glycogen and fats for later use Reactions: glycolysis, the citric acid (Krebs) cycle & oxidative phosphorylation 20  Oxidation-Reduction Reactions and the Role of Coenzymes ▪ Oxidation reactions: involve the gain of O2 or loss of H2 atoms (and their electrons) most biological oxidations involve the loss of hydrogen atoms & are called dehydrogenation reactions E.g., oxidation of glucose involves removal of pairs of hydrogen atoms (with their electrons) until only CO2 remains ▪ Reduction: opposite of oxidation/ the addition of electrons to a molecule ▪ Oxidation-reduction (redox) reactions are always coupled – Oxidized substances lose electrons and energy (donor) – Reduced substances gain electrons and energy (acceptor) 21  Oxidation-Reduction Reactions and the Role of Coenzymes ▪ Redox reactions are catalyzed by enzymes that usually require a B vitamin coenzyme which can accept the hydrogen and its electron, becoming reduced when a substrate is oxidized ▪ Two important coenzymes act as hydrogen (or electron) acceptors in oxidative pathway Nicotinamide adenine dinucleotide (NAD+) Flavin adenine dinucleotide (FAD) 22  ATP Synthesis Two mechanisms are used to make ATP from captured energy that is liberated during cellular respiration 1. Substrate-level phosphorylation – High-energy phosphate groups are directly transferred from phosphorylated substrates to ADP 2. Oxidative phosphorylation ‒ More complex process, but produces most ATP ‒ Carried out by inner mitochondrial membrane proteins in two steps: ‒ Electron Transport chain: energy released via nutrient oxidation used to pump H+ across the inner membrane ‒ Chemiosmotic process: couples movement of substances across membranes to chemical reactions 23  Carbohydrate Metabolism 24 https://ic.pics.livejournal.com/thiruvelan/19136399/2284/2284_900.jpg  Carbohydrate Metabolism Oxidation of Glucose ▪ When glucose enters a cell, it is phosphorylated to glucose-6-phosphate ▪ Most cells (except intestinal cells, kidney and hepatocytes) lack enzymes for reverse reaction, so glucose becomes trapped inside cell Glucose is catabolized via following reaction: C6H12O6 + 6O2 → 6H2O + 6CO2 + 30 ATP + heat glucose oxygen water carbon dioxide Complete glucose catabolism requires three pathways 1. Glycolysis: occurs in the absence of O2 2. Krebs cycle: occurs in the absence of O2 3. Electron transport chain & oxidative phosphorylation 25  Carbohydrate Metabolism Oxidation of Glucose 26  Carbohydrate Metabolism Oxidation of Glucose 1. Glycolysis ▪ Also called glycolytic pathway /anaerobic (no O2 required) ▪ Occurs in the cytosol, involves ten chemical steps ▪ Glucose (6C) → 2 pyruvic acid molecules (3C) Three major phases Phase 1: Sugar activation Glucose is phosphorylated → fructose-1,6-bisphosphate Phase 2: Sugar cleavage Fructose-1,6-bisphosphate is split into 2 -3-carbon fragments Phase 3: Sugar oxidation and ATP formation Six steps involved, with two major events (a) Each 3-C fragment is oxidized by removal of a pair of H, which is picked up by NAD+, forming reduced NADH + H+ H carries a portion of glucose’s energy (b) Inorganic phosphate groups (Pi) are then attached to each oxidized fragment 27  Carbohydrate Metabolism Oxidation of Glucose 1. Glycolysis Final products of glycolysis are: ▪ 2 pyruvic acids (C3H4O3) ▪ 2 reduced NAD+ (NADH + H+) ▪ Net gain of 2 ATP – For glycolysis to continue, more NAD+ must be present to accept more hydrogen atoms Supply of NAD+ is limited NADH must donate its accepted hydrogen atoms to become NAD+ again to be free to pick up more H+ so glycolysis can continue – If oxygen is present, NADH + H+ will transfer its H to proteins in electron transport chain – Occurs in mitochondria – If no oxygen is present, NADH will give hydrogen atoms back to pyruvic acid, reducing it to lactic acid 28  Carbohydrate Metabolism Oxidation of Glucose 2. Citric Acid Cycle (Krebs Cycle) ▪ Occurs in the mitochondrial matrix / does not directly use O2 ▪ Fueled by pyruvic acid (glucose breakdown) and fatty acids from fat breakdown ▪ Pyruvic acid must be actively transported into mitochondria where it enters transitional phase during which its converted to acetyl coenzyme A in 3 steps: 1. Decarboxylation: 1C from pyruvic acid removed → CO2 gas, (expelled by lungs) 2. Oxidation: 2-C fragment oxidized to acetic acid (removed H atoms is picked up by NAD+) 3. Formation of acetyl CoA: acetic acid + coenzyme A form acetyl CoA 29  Carbohydrate Metabolism Oxidation of Glucose 2. Citric Acid Cycle (Krebs Cycle) ▪ CoA shuttles 2 carbon-acetic acid to an enzyme of the Krebs cycle that condenses it with 4C oxaloacetic acid (pickup molecule) thus forming 6C citric acid ▪ During eight steps, original acetic acid is decarboxylated and oxidized to keto acid intermediates, resulting in NADH + H+, FADH2 and CO2 ▪ In final step, oxaloacetic acid regenerated Figure 24.7 Simplified version of the citric acid (Krebs) cycle 30  Carbohydrate Metabolism Oxidation of Glucose For each turn of the cycle, we get: 2 CO2 from decarboxylation 4 molecules of reduced enzymes – 3 NADH + H+ and 1 FADH2 1 ATP (by substrate level phosphorylation) o Started with 2 pyruvic acid molecules, so final products from 1 glucose is doubled – Adding products of transitional phase, total final products for breakdown of 1 glucose are: 6 CO2, 8 NADH + H+, 2 FADH2, and 2 ATP o Note: net gain of 2 ATP molecules o Substrate level phosphorylation 31  Carbohydrate Metabolism Oxidation of Glucose 3. Oxidative Phosphorylation – Electron transport chain (ETC) only pathway to directly use oxygen ▪ NADH + H+ (from glycolysis and Krebs cycle) shuttle H atoms to ETC proteins which combine with O2 to form H2O ‒ Chemiosmosis uses energy released to attach Pi to ADP forming ATP ETC involves chain of carrier proteins (with bound metal atoms called cofactors) embedded in inner mitochondrial membrane ‒ Flavins: proteins derived from riboflavin (ETC complexes I and II ‒ Cytochromes: proteins with iron-containing pigment (III and IV) ‒ Respiratory enzyme complexes: clusters of neighboring carriers that are alternately reduced and oxidized as they pass electrons down the line 32 Focus Figure 24.1 Oxidative Phosphorylation 33  Carbohydrate Metabolism Oxidation of Glucose 3. Oxidative Phosphorylation Phase 1: Electron transport chain ▪ ETC: only pathway that directly uses oxygen – Citric acid cycle will not run if oxygen is not present, but does not directly use oxygen Step 1. Complexes I and II accept hydrogen from NADH and FADH2 respectively NAD+ and FAD can now return to glycolysis and Krebs cycle Step 2. Hydrogen atoms are split into H+ (proton) + electrons (e-) Electrons are passed down chain/energy released with each transfer Each complex is reduced (picking up e-) and then oxidized (transferring e- to the next complex At complex IV electron pairs combine with two H+ and half a molecule of oxygen to form water. Net reaction for ETC Coenzyme-2H + ½ (O2) → Coenzyme + H2O reduced oxidized 34  Carbohydrate Metabolism Oxidation of Glucose 3. Oxidative Phosphorylation Phase 2: Chemiosmosis uses the energy of the proton gradient to synthesize ATP H+ is strongly attracted to the matrix side but can only cross through the membrane protein ATP synthase (complex V) Synthase joins Pi to ADP to make ATP 35  Figure 24.11 Energy yield during cellular respiration C6H12O6 + 6O2 → 6H2O + 6CO2 + 30 ATP o During glycolysis, each glucose (6C) o The pyruvic acid then enters the mitochondrial o Energy-rich electrons picked up by coenzymes (NAD & molecule → 2 pyruvic acid (3C) in the matrix, where the Krebs cycle → CO2. FAD) → ETC, built into the cristae membrane. cytosol. o During glycolysis & the Krebs cycle, small o The ETC carries out oxidative phosphorylation, which amounts of ATP (4) (by substrate-level accounts for most of the ATP generated by cellular phosphorylation.) respiration. 36  Oxidation of Glucose Summary of ATP production Net energy gain from complete oxidation of 1 glucose molecule 1. Substrate-level phosphorylation: 4 ATPs – 2 from glycolysis and 2 from citric acid cycle 2. Oxidative phosphorylation: 28 ATPs – For each NADH + H+ brought in, proton gradient generates 2.5 ATPs 10 NADH + H+ are made, so 25 ATPs – For every FADH2 brought in, only 1.5 ATPs are created 2 FADH2 are made, so 3 ATPs created – Totals between substrate-level phosphorylation and oxidative phosphorylation equal 32 ATPs – But….energy is required to move NADH + H+ generated in glycolysis into mitochondria, which uses up ~2 ATPs, so final total is 30 ATPs produced ▪ There is still uncertainty on final total 37  Glycogenesis, Glycogenolysis & Gluconeogenesis ▪ Cells cannot store large amounts of ATP ▪ Rising intracellular levels of ATP inhibit glucose catabolism and promote glycogen or fat formation ▪ Fats account for 80–85% of stored energy Glycogenesis ▪ Glycogen formation (catalyzed by glycogen synthase) when glucose supplies exceed need for ATP / mostly in liver and skeletal muscle Glycogenolysis ▪ Glycogen breakdown via glycogen phosphorylase in response to low blood glucose / releases glucose monomers Gluconeogenesis ▪ Formation of new (neo) glucose from non- carbohydrate (e.g. glycerol and amino acid) molecules 38 Figure 24.13  Lipid Metabolism 39  Lipid Metabolism ▪ Body’s most concentrated source of energy / key for long-term energy storage & release ▪ Lipids provide a greater energy yield than from glucose or protein catabolism – Fat catabolism yields 9 kcal per gram versus 4 kcal per gram of carbohydrate or protein ▪ Most products of fat digestion are transported in lymph as chylomicrons ▪ Hydrolyzed by endothelial enzymes into fatty acids and glycerol 40  Lipid Metabolism Only triglycerides (TGs) are routinely oxidized for energy Two building blocks of TGS are oxidized separately 1.Glycerol breakdown ▪ Glycerol is broken down into glyceraldehyde 3- phosphate (same as in glycolysis), which then enters citric acid cycle – Yields 15 ATP/glycerol 2. Fatty acid breakdown ▪ Fatty acids undergo beta oxidation in mitochondria: ▪ FAs: broken into 2C acetic acid fragments/coenzymes (FAD and NAD+) are reduced ▪ Acetic acid fragment fuses with CoA to form acetyl CoA, which enters citric acid cycle – Reduced coenzymes enter electron transport chain ▪ Referred to as “beta” oxidation because two carbons are broken off fatty acid chain, allowing third-position carbon to be oxidized 41  Lipid Metabolism Lipogenesis ▪ TG synthesis occurs when cellular ATP and glucose levels are high ▪ Dietary glycerol and fatty acids not needed for energy are stored as triglycerides o 50% is stored in adipose tissue; other 50% is deposited in other areas ▪ Excess ATP causes accumulation of acetyl CoA and glyceraldehyde 3-phosphate o Acetyl C o A molecules are joined, forming fatty acid chains that grow two carbons at a time (so almost all fatty acids in body contain an even number) Lipolysis ▪ breakdown of stored lipids into glycerol & FAs; reverse of lipogenesis – FAs are actually preferred by liver, cardiac muscle, resting skeletal muscle for fuel – Lipolysis is accelerated when carbohydrate intake is inadequate ▪ Beta oxidation of the released fatty acids results in production of large amounts of acetyl CoA which can enter citric acid cycle only if enough carbohydrate intermediates are available Without oxaloacetic acid fat oxidation is incomplete, and Acetyl CoA accumulates ▪ The liver converts acetyl-CoA to ketone bodies (ketogenesis) ▪ Ketone bodies include acetoacetic acid, β-hydroxybutyric acid, and acetone 42 Lipid Metabolism Figure 24.16 Lipid metabolism 43  Protein Metabolism https://o.quizlet.com/h3OKFQEGPRkILCM.xbWj5Q.png 44  Protein Metabolism ▪ Proteins deteriorate, so they need to be continually broken down and replaced ▪ Amino acids are recycled into new proteins or different compounds ▪ Cells use amino acids to replace tissue proteins at a rate of ~100 g/day ▪ Proteins are not stored in body – When dietary proteins are in excess, amino acids are: Oxidized for energy Converted to fat or glycogen for storage Degradation of Amino Acids ▪ Goal is to produce molecules that can be used for energy in citric acid cycle or converted to glucose Three events of amino acid degradation Transamination / Oxidative deamination / Keto acid modification  Protein Metabolism 46 Figure 24.17 Processes that occur when amino acids are utilized for energy.  Protein Metabolism Degradation of Amino Acids 1. Transamination: many amino acids can transfer their amine group to α- ketoglutaric acid (a citric acid cycle keto acid), transforming it into glutamic acid ▪ original aa becomes a keto acid ▪ glutamic acid is an intermediate keto acid of the citric acid cycle 2. Oxidative deamination: In the liver, amine group of glutamic acid is removed as ammonia (NH3) ▪ α-ketoglutaric acid is regenerated ▪ NH3 then combines with CO2 to form urea & water ▪ Urea is released to blood and excreted in urine 3. Keto acid modification: Keto acids formed from transamination are altered to produce metabolites that can enter citric acid cycle ▪ Major metabolites produced: pyruvic acid, acetyl CoA, α-ketoglutaric acid, oxaloacetic acid ▪ Glycolysis reactions are reversible, so pyruvic acid metabolites formed can be reconverted to glucose 47  Protein Metabolism Protein Synthesis ▪ Amino acids are most important anabolic nutrients – Form all proteins as well as bulk of functional molecules ▪ Protein synthesis that occurs on ribosomes is hormonally controlled (example: growth hormone, thyroid hormone, sex hormones) ▪ Synthesis requires complete set of amino acids – Essential amino acids must be acquired in diet 48 Metabolic States of the Body 49  Catabolic-Anabolic Steady State ▪ Dynamic state in which organic molecules (except DNA) are continuously broken down and rebuilt (catabolic- anabolic balance) ▪ Body uses nutrient pools: amino acids, carbohydrates, fats ▪ Pools are interconvertible because pathways are linked by common intermediates ▪ Amount and direction of conversion are directed by liver, adipose tissue, and skeletal muscle ▪ Organs have different fuel preferences Amino Acid pool Carbohydrate and Fat Pools ▪ body’s total supply of free amino ▪ Easily interconverted through key acids intermediates ▪ Proteins are lost in urine, hair, and ▪ Differ from the amino acid pool in skin cells; replaced by diet that: – Fats & CHOs are oxidized ▪ Pool is the source for directly to produce energy – Resynthesizing body proteins – Excess carbohydrate and fat can – Forming amino acid derivatives be stored as such (aa not stored – Gluconeogenesis as proteins) 50 Interconversion of carbohydrates, fats and proteins 51  FED STATE ▪ Fed state also called absorptive state (~4 hrs. after eating); absorption of nutrients is occurring ▪ Anabolism exceeds catabolism; excess nutrients are stored as fats ▪ Dietary amino acids and fats used to remake degraded body protein or fat ▪ Excess nutrients (regardless of source) transformed to fat 52  Hormonal Control of the Fed state – Absorptive state is controlled primarily by insulin – Insulin secretion by beta cells of pancreas is stimulated by: ▪ Elevated blood levels of glucose ▪ Elevated blood levels of FAs and AAs ▪ acetylcholine is released by parasympathetic nerve fibers ▪ Intestinal GIP (glucose-dependent insulinotropic peptide) – Insulin facilitates the glucose uptake – Insulin is a hypoglycemic hormone that enhances: ▪ Glucose oxidation for energy ▪ Glycogen and triglyceride formation ▪ Active transport of amino acids into tissue cells ▪ Protein synthesis 53  Hormonal Control of the Fed state – It also inhibits glucose release from liver and gluconeogenesis – Insulin lowers blood glucose levels in three ways: ▪ Enhances membrane transport of glucose into fat and muscle cells ▪ Inhibits breakdown of glycogen to glucose ▪ Inhibits conversion of amino acids or fats to glucose Net Effect of Insulin ↓ Blood glucose ↑ glycogen storage ↓ Blood amino acids & FFA 54  FASTING STATE ▪ also called postabsorptive state, when GI tract is empty, and energy is supplied by breakdown of body’s reserves ▪ Catabolism of fat, glycogen, and proteins exceeds anabolism Goal: maintain blood glucose within normal range between meals ▪ by making glucose available to blood and promoting the use of fats for energy ▪ Glucose sparing saves glucose for organs that need it most, such as brain 55  FASTING STATE Sources of blood glucose 1. Glycogenolysis in liver: first reserve used 2. Glycogenolysis in skeletal muscle: before glucose from liver is exhausted, glycogen stores in skeletal muscles start to break down 3. Lipolysis in adipose tissues and liver ▪ Glycerol used for gluconeogenesis in liver 4. Catabolism of cellular protein: major source during prolonged fasting; liver converts amino acids to glucose (gluconeogenesis). ▪ limited amount of protein can be broken down before damage ▪ Amount of fat in body determines how long a person can survive without food Glucose Sparing: ‒ During prolonged fasting, body uses more noncarbohydrate fuels to conserve glucose ‒ Brain uses bulk of glucose while other body cells switch to fatty acids as main fuel 56  Hormonal and neural control of the fasting state Glucagon: hyperglycemic hormone whose release is stimulated by: ▪ Declining blood glucose levels / rising amino acid levels. ▪ Glucagon promotes: – Glycogenolysis and gluconeogenesis in the liver – Lipolysis in adipose tissue, causing FAs and glycerol to be released ▪ SNS interacts with several hormones to control events of postabsorptive state Sympathetic fibers innervate adipose tissue, releasing norepinephrine to stimulate lipolysis – Release of epinephrine from adrenal medulla targets liver, skeletal muscle, and adipose to mobilize fat and promote glycogenolysis Net Effect of Glucagon – Pathway stimulates by anything that triggers ↑ Blood glucose ↓ glycogen storage the fight-or-flight response ↑ Blood amino acids & FFA 57  The previous slide marks the end of the content that will be evaluated on Midterm 1 (February 7th) 58