Energy Metabolism PDF

NUTR 250 Human Nutrition & Metabolisms Chapter 9 Energy Metabolism Dr. Keting Li, FDST, UNL Chapter Topics -ISMs: Metabolism, catabolism, anabolism Oxidation & Reduction Metabolic pathways: ATP production from CHO, fats, protein Gluconeogenesis ATP production from alcohol Feasting and Fasting Inborn...

NUTR 250 Human Nutrition & Metabolisms Chapter 9 Energy Metabolism Dr. Keting Li, FDST, UNL Chapter Topics -ISMs: Metabolism, catabolism, anabolism Oxidation & Reduction Metabolic pathways: ATP production from CHO, fats, protein Gluconeogenesis ATP production from alcohol Feasting and Fasting Inborn errors of metabolism Metabolism The entire network of chemical processes essential for life: Gain energy from CHO, fat, protein, alcohol Synthesize of new substances Excrete of waste products Metabolic pathway A group of biochemical reactions that occur in a progression from beginning to end Catabolic pathway or Anabolic pathway Anabolism vs. Catabolism Anabolic pathway Small compounds → larger, complex compounds Building blocks: glucose, fatty acids, cholesterol, amino acids Require energy e.g., gluconeogenesis Catabolic pathway Breakdown of larger compounds: glycogen, TG, proteins Release Energy (ATP) e.g., glycolysis Converting Food into Energy + Heat + H2O ATP: Adenosine Triphosphate The cellular energy “currency” Energy in ATP is used directly for: Synthesis of new compounds Muscle contraction Conducting nerve impulses Pumping ions across membranes High-energy phosphate bond Hydrolysis of high-energy phosphate bonds releases energy. ATP 1. Hydrolysis of ATP: 1 Energy produces adenosine diphosphate (ADP) 2. Hydrolysis of ADP: Energy produces adenosine monophosphate (AMP) ATP Recycling ATP is regenerated by adding phosphate back to ADP; ADP is regenerated by adding phosphate back to AMP; involves the exchange of electrons in the form of H+. Essential survival strategy Cells constantly break down ATP and regenerate it! (Sedentary adult breaks down and resynthesizes about 40 kg of ATP each day) Oxidation-Reduction reactions (Redox) A type of chemical reaction that involves a transfer of electrons between two species e.g., cellular respiration is the oxidation of glucose to CO2 and the reduction of oxygen to water. C6H12O6 + 6 O2 → 6 CO2 + 6 H2O C6H12O6 → 6 CO2 O2 → 2 H 2 O Energy Carriers A small class of compounds functions as mobile electron carrier; derived from the B vitamin group and are derivatives of nucleotides nicotinamide adenine dinucleotide (NAD), nicotinamide adenine dinucleotide phosphate (NADP), and flavin adenine dinucleotide (FAD) NAD+/NADH; NADP+/NADPH; FAD/FADH2 oxidized form: NAD+ reduced form: NADH ATP Production from Carbohydrates The production of ATP is achieved through the oxidation of glucose molecules Aerobic: In presence of O2 Creates 30-32 ATP from 1 glucose Anaerobic: Without O2 Creates 2 ATP from 1 glucose Anaerobic vs Aerobic Metabolism Aerobic respiration 1. 2. 3. 4. Glycolysis Pyruvate oxidation TCA cycle Oxidative phosphorylation Energy investment phase Aerobic respiration 1. Glycolysis Glucose converted to 2 units of pyruvate Initially requires 2 ATPs, however, generates 4 ATP – net gain of 2 ATP; 2 NADH Two roles: generate energy and provide building blocks for synthesizing other needed compounds Glyceraldehyde-3-P dehydrogenase Energy payoff phase Aerobic respiration 2 ATP 2 NAD+ 2 Pi 4 ATP 2 NADH 2 H2O Glucose 2 Pyruvate Net gain: 2 ATP and 2 NADH Glycolysis song Aerobic respiration 2. Pyruvate oxidation (transition reaction) Conversion of pyruvate to acetyl-CoA; catalyzed by pyruvate dehydrogenase; irreversible Transition from glycolysis to the TCA cycle A deficiency of pyruvate dehydrogenase can result in lactic acidosis 2 NADH Aerobic respiration 3. Tricarboxylic acid cycle (TCA) Krebs cycle, Citric Acid Cycle A series of chemical reactions to generate energy via the oxidation of acetyl-CoA 2 ATP 6 NADH 2 FADH2 Aerobic respiration TCA cycle 4 H2O 2 FAD 6 NAD+ 2 GDP 2 CoASH 2 GTP 2 FADH 6 NADH + H+ 4 CO2 2 Acetyl-CoA (Activated Acetate) TCA Cycle (8 reactions) Aerobic respiration Aerobic respiration 4. Oxidative phosphorylation Almost 90% of the ATP is produced Two closely connected components: the electron transport chain (ETC) + chemiosmosis In ETC, electron (delivered by reduced electron carriers NADH and FADH2) are passed from one molecule to another, and energy released is used to form an electrochemical gradient. O2 sits at the end of ETC and accepts electron and picks up protons to form water In chemiosmosis, the energy stored in the gradient is used to make ATP by ATP synthase. ATP Production from glucose + O2 * * Each NADH from glycolysis produces net 1.5 ATP (due to NADH transport over the mitochondrial membrane) or 2.5 ATP. The amount depends on the tissue. Anaerobic respiration Anaerobic conditions Pyruvate is converted to lactate instead of acetyl-CoA  Quickly produce ATP, 2 ATP  Gluconeogenesis in the liver Only way to make ATP for cells that lack mitochondria (e.g., red blood cells) Cori Cycle High intensity exercise rely heavily on anaerobic glycolysis Lactate produced by anaerobic glycolysis is transported to the liver and converted to glucose, then, returned to the muscle ATP Production from Fats 1. Lipolysis: triglycerides are broken down into their constituent molecules Enzyme: Lipases Products: Glycerol goes through glycolysis (glycerol → glycerol 3-p →Dihydroxyacetone-P) Free fatty acids taken up by cells; shuttled into mitochondria 2. Fatty acid oxidation (beta-oxidation): Breakdown of fatty acids; 2-carbon groups are cleaved (acetyl-CoA) Occurs in the mitochondria Acetyl-CoA enters citric acid cycle Stages of fatty acid oxidation Example: palmitic acid (C16) Step 1: fatty acids activation palmitic acid to palmitoyl-CoA (Acyl-CoA synthetase) Input of 2 ATP equivalents Step 2: Imported into mitochondrial matrix Step 3: Fatty acid break down Stage 1 breaks fatty acids into acetyl-CoA, called β-oxidation and generates NADH and FADH2 Stage 2 oxidizes acetyl-CoA into CO2 with the TCA cycle (and generation NADH and FADH2) Stage 3 generates ATP from NADH and FADH2 via the mitochondrial electron transport chain How much ATP do we get from “burning” (i.e. oxidizing) 1 16:0 fatty acid? 1. Fatty acid activation: 16:0 + ATP + CoASH → 16:0-CoA + AMP + PPi Input of 2 ATP equivalents PPi + H2O → 2 Pi 2. β-Oxidation (7 rounds) 16:0-CoA + 7 FAD + 7 H2O +7 NAD+ + 7 CoASH → 8 Acetyl-CoA + 7 NADH + 7 FADH2 3. TCA Cycle (8 rounds) 8 Acetyl-CoA + 8 FAD + 24 NAD+ 16 H2O + 8 ADP → 24 NADH + 8 FADH2 + 8 ATP + 16 CO2 4. Electron Transport Chain 31 NADH + 15 FADH2 + 23 O2 → 77.5 ATP + 22.5 ATP + 46 H2O 8 + 77.5 + 22.5 - 2 = 106 ATP ATP Production from Carbohydrates and Fats Pathway Substrate O2 CHO - anaerobic 1. Glycolysis Glucose No CHO - aerobic 1. Glycolysis Glucose Yes NADH+H+ FADH2 GTP +2 -2 +4 Net: +2 Activation -2 +2 2. Pyruvate oxidation +2 3. Citric Acid Cycle +6 +2 +2 Net: +30-32 4. Oxidative phosphorylation Fat 1. Beta-Oxidation 2. Citric Acid Cycle ATP Fatty Acid (e.g. C16) Yes +7 +7 +24 +8 Activation -2 +8 Net: +106 3. Electron Transport Chain 2.5 ATP per NADH, 1.5 ATP per FADH2 ATP Production from Fats Fats yield more energy than carbohydrates 9 kcal/g vs 4 kcal/g 1. FAs contain more C atoms than glucose → more acetylCoA enter citric acid cycle 16C fatty acid: 8 acetyl-CoA 6C glucose: 2 acetyl-CoA 2. Fatty acids have fewer O atoms than glucose Palmitic acid: C16H32O2 Glucose: C6H12O6 FA carbon yield about 7 ATP; glucose carbon yield about 5 ATP CHOs aid Fat Metabolism Citric acid cycle requires oxaloacetate Source of oxaloacetate: pyruvate (from CHO) Ketones By-produces of fat catabolism inadequate oxaloacetate to allow acetyl-CoA to enter TCA cycle Occurs with hormonal imbalance (insufficient insulin) - ketosis Destination: most are converted back into acetyl-CoA in other body cells Used as energy (heart, muscles, brain) Leave the body via lung (acetone) Acetone Acetoacetic acid Beta-hydroxybutyric acid Ketosis in Semistarvation or Fasting Diabetic Ketosis (Type 1 Diabetes) Little or no insulin produced in type 1 diabetes Cells cannot take up glucose -> rapid lipolysis Excessive ketone production o Excretion via urine (mineral imbalance) o Acidosis (or diabetic ketoacidosis) Semistarvation or Fasting Low glucose and insulin levels -> Lipolysis Ketones serve as fuel Adaptive response to spare protein The need for glucose as body fuel diminishes, reduce the need for liver and kidney to produce from amino acids Protein Metabolism Breakdown of Amino Acids for fuel Liver: primary site Muscle: Branched-chain amino acids (Leucine, Isoleucine, Valine) First step: Deamination Results in carbon skeleton (acetyl-CoA, pyruvate, citric acid cycle intermediates) Requires vitamin B-6 Protein Metabolism Glucogenic amino acids: Form pyruvate, or bypass acetylCoA and enter the citric acid cycle Carbon skeleton is used to form glucose Ketogenic amino acids: Carbon skeleton become acetylCoA for ketone body synthesis; When insulin levels are low, become ketones Exclusively ketogenic: lysine and leucine Disposal of Excess Amino Groups from Amino Acid Metabolism Amino acid catabolism yields amino groups Converted to ammonia (NH3 = toxic to brain!) Urea cycle Liver converts the amino groups for excretion in the urine (kidney) with the urea cycle Alcohol Metabolism 1. Alcohol dehydrogenase pathway (low level intake) Alcohol → acetaldehyde → acetyl-CoA Result: 2 NADH + H+ Small amount of acetyl-CoA can enter citric acid cycle But NADH build up slows citric acid cycle Acetyl-CoA directed to fatty acid and triglyceride production (steatosis) 2. MEOS (moderate-to-excessive consumption) Requires O2 and NADPH + H+ Role of Liver Key metabolic functions: 1. Conversions of sugars 2. Fat synthesis 3. Production of ketones 4. Amino acid metabolism 5. Urea production 6. Alcohol metabolism 7. Nutrient storage “First pass” Most nutrients pass through liver after absorption Regulation of Energy Metabolism Regulation involves ATP concentrations Enzymes Hormones Vitamins Minerals Regulation of Energy Metabolism ATP concentrations High ATP ↓ ATP synthesis and energy-yielding reactions ↑ Anabolic reactions High ADP ↑ ATP synthesis and energy-yielding reactions Enzymes: Presence Rate of activity Synthesis controlled by cells and reaction products Example: A high protein diet leads to increased synthesis of enzymes associated with amino acid metabolism and gluconeogenesis. Regulation of Energy Metabolism Hormones: High insulin ↑ Glycogen synthesis ↑ Fat synthesis ↑ Protein synthesis Low Insulin ↑ Gluconeogenesis ↑ Lipolysis ↑ Protein breakdown Regulation of Energy Metabolism Vitamins and minerals needed for metabolism Thiamin (B1) Riboflavin (B2) Niacin (B3) Pantothenic acid (B5) Pyridoxine (B6) Biotin (B7) Folate (B9) Cobalamin (B12) Iron Copper Feasting and Fasting Feasting Most obvious result: fat accumulation Other adaptations: ↑ Insulin ↑ Burning of glucose ↑ Glycogen synthesis ↑ Protein and fat synthesis Feasting Excess fat Stored in adipose tissue (little energy required) -> High fat, high energy diets promote adiposity Excess protein Does not promote muscle synthesis Amino acids will stay in “pool” or form fatty acids Excess carbohydrates First into glycogen stores Used for energy or fat synthesis Anyone who consumes more calories from any energy-yielding nutrients than what the body can use will gain weight. Lipogenesis The pathways for the synthesis of fat from excess carbohydrate or protein Primarily in liver Link the acetyl-CoA (from either glucose or ketogenic amino acids) to palmitic acid (16 C) Key enzyme: fatty acid synthase Stimulated by insulin Lipogenesis Synthesis of long-chain fatty acids from substrates other than lipids Means by which excess CHO can be laid down as fat Regulated by insulin (↑gene expression) Occurs in liver and adipose Not active in muscle De Novo lipogenesis: not of major importance in humans unless: - very high CHO diet for several days - overfeeding for consecutive days - intravenous feeding while recovering Abbreviation: GK, glucokinase; DHAP, dihydroxyacetone phosphate; PEP, from illness phosphoenol pyruvate; PK, pyruvate kinase; ATP:CL, ATP citrate lyase; ACC, acetyl-CoA carboxylase; FAS, fatty acid synthase Fuel Reserves Well-fed 70 kg human has fuel reserves ~170,000 kcal Energy needed for a 24-hr period is 1,600-6,000 kcal Sufficient reserves for starvation up to 1-3 months But, glucose+glycogen reserves are exhausted in 2 days) Glucose oxidation Ketolysis Once glycogen stores are depleted Proteolysis ↑ in muscle and liver to provide gluconeogenic substrates to liver Proteolysis Lipolysis ↑ in adipose tissue β-Oxidation TCA cycle Ketogenesis ↑ in liver Proteolysis↓ Gluconeo -genesis Ketogenesis β-Oxidation Glycolysis Gluconeo -genesis Lipolysis insulin is low while glucagon is elevated Fuel Metabolism in Prolonged Starvation 3-day versus 40-day starvation