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Nutrition, Metabolism, and Body Temperature Regulation Nutrition • Nutrient – a substance that promotes normal growth, maintenance, and repair • Major nutrients – carbohydrates, lipids, and proteins • Other nutrients – vitamins and minerals (and technically speaking, water) Carbohydrates • Complex carbohydrates (starches) are found in bread, cereal, flour, pasta, nuts, and potatoes • Simple carbohydrates (sugars) are found in soft drinks, candy, fruit, and ice cream • Glucose is the molecule ultimately used by body cells to make ATP • Neurons and RBCs rely almost entirely upon glucose to supply their energy needs • Excess glucose is converted to glycogen or fat and stored Lipids • The most abundant dietary lipids, triglycerides, are found in both animal and plant foods • Essential fatty acids – linoleic and linolenic acid, found in most vegetables, must be ingested • Dietary fats: – Help the body to absorb vitamins – Are a major energy fuel of hepatocytes and skeletal muscle – Are a component of myelin sheaths and all cell membranes Proteins • Proteins supply: – Essential amino acids, the building blocks for nonessential amino acids – Nitrogen for nonprotein nitrogen-containing substances • Daily intake should be approximately 0.8g/kg of body weight Vitamins • Organic (carbon) compounds needed for growth and good health • They are crucial in helping the body use nutrients and often function as coenzymes • Only vitamins D, K, and B are synthesized in the body; all others must be ingested • Water-soluble vitamins (B-complex and C) are absorbed in the gastrointestinal tract – B12 additionally requires gastric intrinsic factor to be absorbed Minerals • Seven minerals are required in moderate amounts – Calcium, phosphorus, potassium, sulfur, sodium, chloride, and magnesium • Dozens are required in trace amounts • Minerals work with nutrients to ensure proper body functioning • Calcium, phosphorus, and magnesium salts harden bone Minerals • Sodium and chloride help maintain normal osmolarity, water balance, and are essential in nerve and muscle function • Uptake and excretion must be balanced to prevent toxic overload Metabolism • Metabolism – all chemical reactions necessary to maintain life • Cellular respiration – food fuels are broken down within cells and some of the energy is captured to produce ATP – Anabolic reactions – synthesis of larger molecules from smaller ones – Catabolic reactions – hydrolysis of complex structures into simpler ones Metabolism • Enzymes shift the high-energy phosphate groups of ATP to other molecules • These phosphorylated molecules are activated to perform cellular functions Stages of Metabolism • Energy-containing nutrients are processed in three major stages 1. Digestion – breakdown of food; nutrients are transported to tissues 2. Anabolism and formation of catabolic intermediates where nutrients are: 1. Built into lipids, proteins, and glycogen 2. Broken down by catabolic pathways to pyruvic acid and acetyl CoA 3. Oxidative breakdown – nutrients are catabolized to carbon dioxide, water, and ATP Stages of Metabolism Carbohydrate Metabolism • Since all carbohydrates are transformed into glucose, it is essentially glucose metabolism • Oxidation of glucose is shown by the overall reaction: C6H12O6 + 6O2 6H2O + 6CO2 + 36 ATP + heat • Glucose is catabolized in three pathways 1. Glycolysis 2. Krebs cycle 3. The electron transport chain and oxidative phosphorylation Carbohydrate Catabolism Glycolysis • A three-phase pathway in which: 1. Glucose is oxidized into pyruvic acid 2. NAD+ is reduced to NADH + H+ 3. ATP is synthesized by substrate-level phosphorylation • Pyruvic acid: – Moves on to the Krebs cycle in an aerobic pathway (with O2) – Is reduced to lactic acid in an anaerobic environment (if no O2) 3 Outcomes of Glycolysis 3. ATP is synthesized by substrate-level phosphorylation 2. NAD+ is reduced to NADH + H+ 1. Glucose is oxidized into pyruvic acid Glycolysis: Phase 1 and 2 • Phase 1: Sugar activation – Two ATP molecules activate glucose into fructose-1,6-diphosphate • Phase 2: Sugar cleavage – Fructose-1,6-bisphosphate is cleaved into two 3-carbon isomers • Bishydroxyacetone phosphate • Glyceraldehyde 3-phosphate Glycolysis: Phase 3 • Phase 3: Oxidation and ATP formation – The 3-carbon sugars are oxidized (reducing NAD+) – Inorganic phosphate groups (Pi) are attached to each oxidized fragment – The terminal phosphates are cleaved and captured by ADP to form four ATP molecules Glycolysis: Phase 3 • The final products are: 1. Two pyruvic acid molecules 2. Two NADH + H+ molecules (reduced NAD+) 3. A net gain of two ATP molecules Krebs Cycle: Preparatory Step • Occurs in the mitochondrial matrix and is fueled by pyruvic acid and fatty acids Krebs Cycle: Preparatory Step • Pyruvic acid is converted to acetyl CoA in three main steps: 1. Decarboxylation • • Carbon is removed Carbon dioxide is released 2. Oxidation • • Hydrogen atoms are removed from pyruvic acid NAD+ is reduced to NADH + H+ 3. Formation of acetyl CoA – the resulting acetic acid is combined with coenzyme A, a sulfur-containing coenzyme, to form acetyl CoA Krebs Cycle • An eight-step cycle in which each acetic acid is decarboxylated and oxidized, generating: 1. 2. 3. 4. • Three molecules of NADH + H+ One molecule of FADH2 Two molecules of CO2 One molecule of ATP For each molecule of glucose entering glycolysis, two molecules of acetyl CoA enter the Krebs cycle Krebs Cycle Electron Transport Chain • Food (glucose) is oxidized and the released hydrogens: 1. Are transported by coenzymes NADH and FADH2 2. Enter a chain of proteins bound to metal atoms (cofactors) 3. Combine with molecular oxygen to form water 4. Release energy • The energy released is harnessed to attach inorganic phosphate groups (Pi) to ADP, making ATP by oxidative phosphorylation Mechanism of Oxidative Phosphorylation • The hydrogens delivered to the chain are split into protons (H+) and electrons – The protons are pumped across the inner mitochondrial membrane by: • NADH dehydrogenase (FMN, Fe-S) • Cytochrome b-c1 • Cytochrome oxidase (a-a3) – The electrons are shuttled from one acceptor to the next Mechanism of Oxidative Phosphorylation 1. Electrons are delivered to oxygen, forming oxygen ions 2. Oxygen ions attract H+ to form water 3. H+ pumped to the intermembrane space: – Diffuses back to the matrix via ATP synthase – Releases energy to make ATP Mechanism of Oxidative Phosphorylation 1. Hydrogens are split into protons and electrons Mechanism of Oxidative Phosphorylation 2. Protons are shuttled across membrane Mechanism of Oxidative Phosphorylation 3. Electrons cross membrane as well but fall back sooner Mechanism of Oxidative Phosphorylation 4. When electrons fall back, you have 2 gradients, a pH gradient and a strong charge gradient Mechanism of Oxidative Phosphorylation 5. When H comes back, it can give off energy that is used to make ATP Summary of ATP Production Lipid Metabolism • Most products of fat metabolism are transported in lymph as chylomicrons • Lipids in chylomicrons are hydrolyzed by plasma enzymes and absorbed by cells • Catabolism of fats involves two separate pathways Glycerol Fatty Acids – Glycerol pathway – Fatty acids pathway Lipid Metabolism Lipogenesis and Lipolysis • Excess dietary glycerol and fatty acids undergo lipogenesis to form triglycerides • Glucose is easily converted into fat since acetyl CoA is: – An intermediate in glucose catabolism – The starting molecule for the synthesis of fatty acids Lipogenesis and Lipolysis • Lipolysis, the breakdown of stored fat, is essentially lipogenesis in reverse • Oxaloacetic acid is necessary for the complete oxidation of fat – Without it, acetyl CoA is converted into ketones (ketogenesis) Lipogenesis and Lipolysis The main point here is that lipids and sugars are interconvertible Protein Metabolism • Excess dietary protein results in amino acids being: – Oxidized for energy – Converted into fat for storage • Amino acids must be deaminated prior to oxidation for energy Protein Metabolism Synthesis of Proteins • Amino acids are the most important anabolic nutrients, and they form: – All protein structures – The bulk of the body’s functional molecules State of the Body • The body exists in a dynamic catabolicanabolic state • Organic molecules (except DNA) are continuously broken down and rebuilt • The body’s total supply of nutrients constitutes its nutrient pool Absoprtive and Postabsorptive States • Metabolic controls equalize blood concentrations of nutrients between two states • Absorptive – The time during and shortly after nutrient intake • Postabsorptive – The time when the GI tract is empty – Energy sources are supplied by the breakdown of body reserves Absorptive State (Full Stomach) • The major metabolic thrust is anabolism and energy storage – Amino acids become proteins – Glycerol and fatty acids are converted to triglycerides – Glucose is stored as glycogen • Dietary glucose is the major energy fuel • Excess amino acids are deaminated and used for energy or stored as fat in the liver Absorptive State Principal Pathways of the Absorptive State • In muscle: – Amino acids become protein – Glucose is converted to glycogen • In the liver: – Amino acids become protein or are deaminated to keto acids – Glucose is stored as glycogen or converted to fat Principal Pathways of the Absorptive State • In adipose tissue: – Glucose and fats are converted and stored as fat • All tissues use glucose to synthesize ATP Principal Pathways of the Absorptive State Insulin Effects on Metabolism • Insulin controls the absorptive state and its secretion is stimulated by: – Increased blood glucose – Elevated amino acid levels in the blood – Gastrin, CCK, and secretin • Insulin enhances: – Active transport of amino acids into tissue cells – Facilitated diffusion of glucose into tissue Insulin Effects on Metabolism Diabetes Mellitus • A consequence of inadequate insulin production (Type I) or abnormal insulin receptors (Type II) • Glucose becomes unavailable to most body cells • Metabolic acidosis, protein wasting, and weight loss result as fats and tissue proteins are used for energy Postabsorptive State • The major metabolic thrust is catabolism and replacement of fuels in the blood – Proteins are broken down to amino acids – Triglycerides are turned into glycerol and fatty acids – Glycogen becomes glucose • Glucose is provided by glycogenolysis and gluconeogenesis • Fatty acids and ketones are the major energy fuels • Amino acids are converted to glucose in the liver Postabsorptive State Principle Pathways in the Postabsorptive State • In muscle: – Protein is broken down to amino acids – Glycogen is converted to ATP and pyruvic acid (lactic acid in anaerobic states) Principle Pathways in the Postabsorptive State • In the liver: – Amino acids, pyruvic acid, stored glycogen, and fat are converted into glucose – Fat is converted into keto acids that are used to make ATP • Fatty acids (from adipose tissue) and ketone bodies (from the liver) are used in most tissue to make ATP • Glucose from the liver is used by the nervous system to generate ATP Principle Pathways in the Postabsorptive State Hormonal and Neural Controls of the Postabsorptive State • Decreased plasma glucose concentration and rising amino acid levels stimulate alpha cells of the pancreas to secrete glucagon (the antagonist of insulin) • Glucagon stimulates: – Glycogenolysis and gluconeogenesis – Fat breakdown in adipose tissue – Glucose sparing Hormonal and Neural Controls of the Postabsorptive State • In response to low plasma glucose, the sympathetic nervous system releases epinephrine, which acts on the liver, skeletal muscle, and adipose tissue to mobilize fat and promote glycogenolysis Cholesterol • Is the structural basis of bile salts, steroid hormones, and vitamin D • Makes up part of the hedgehog molecule that directs embryonic development • Is transported to and from tissues via lipoproteins Cholesterol • Lipoproteins are classified as: – HDLs – high-density lipoproteins have more protein content – LDLs – low-density lipoproteins have a considerable cholesterol component – VLDLs – very low density lipoproteins are mostly triglycerides Lipoproteins • High levels of HDL are thought to protect against heart attack • High levels of LDL, especially lipoprotein (a), increase the risk of heart attack Metabolic Rate • Rate of energy output (expressed per hour) equal to the total heat produced by: – All the chemical reactions in the body – The mechanical work of the body • Measured directly with a calorimeter or indirectly with a respirometer Metabolic Rate • Basal metabolic rate (BMR) – Reflects the energy the body needs to perform its most essential activities • Total metabolic rate (TMR) – Total rate of kilocalorie consumption to fuel all ongoing activities Factors that Influence BMR • Surface area, age, gender, stress, and hormones • As the ratio of surface area to volume increases, BMR increases • Males have a disproportionately high BMR • Stress increases BMR • Thyroxine increases oxygen consumption, cellular respiration, and BMR