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Metabolism Metabolism • All the biochemical reactions occurring in the body • Generating, storing, and expending energy • ATP • Supports body activities • Assists in constructing new tissue Metabolism • Two types of reactions • Catabolism • Breakdown of molecules • Releases energy • Anabolism • Synthesis of molecules • Requires energy Energy • Capacity to do work or put matter into motion • Force x distance • Types of energy: • Kinetic • Objects are moving • Potential • Stored (inactive) energy • Chemical energy • Potential energy stored in bonds of chemical substances Energy • Kinetic energy • Electromagnetic energy • Moving photons from the sun and stars • Heat • Movement of water or gas molecules • Potential energy • Energy used to increase the level of complexity in an object Energy • Chemical energy • Moving atoms may collide and form bonds • Increased complexity increases stored potential energy Energy • Greatest amount of energy in an atom is within nucleus • May be used or altered by biological processes Bonds and Bond Energy • Chemical energy of a molecule • Electron distance from nucleus • Moving closer to nucleus = energy released • Moving away from nucleus = energy added • Electronegativity • Ability of an atom to attract an electron to itself • Oxygen is very electronegative Bonds and Bond Energy • Covalent bonds • Bond energy • Energy required to break bonds • High energy molecules • • • • Carbohydrates, fats and amino acids C-C and C-H bonds Unstable Logical food sources • Low energy bonds • Atoms bonded to oxygen • C=O • Stable Bonds and Bond Energy • Bottom line • Energy is always released when bonds are formed • Amount of energy released is related to final position of bonding electrons Stages of Metabolism Processing of nutrients 1. 2. Digestion, absorption and transport to tissues Cellular processing in cytoplasm • • 3. Synthesis of lipids, proteins, and glycogen, or Catabolism (glycolysis) into intermediates Oxidative (mitochondrial) breakdown of intermediates into CO2, water, and ATP Stage 1 Digestion in GI tract lumen to absorbable forms. Transport via blood to tissue cells. PROTEINS CARBOHYDRATES Amino acids Glucose and other sugars Stage 2 Anabolism Proteins (incorporation into molecules) and catabolism of nutrients NH3 to form intermediates within tissue cells. FATS Glycerol Glycogen Glucose Fatty acids Fats Pyruvic acid Acetyl CoA Stage 3 Oxidative breakdown of products of stage 2 in Infrequent mitochondria of tissue cells. CO2 is liberated, and H atoms removed are ultimately delivered to molecular oxygen, forming water. Some energy released is used to form ATP. Krebs cycle H CO2 Oxidative phosphorylation (in electron transport chain) O2 H2O Catabolic reactions Anabolic reactions Figure 24.3 Carbohydrate Metabolism • Body’s preferred energy source • All cells possess enzymes to metabolize it • Galactose, fructose, and glucose may be directly absorbed • Galactose and fructose must be converted to glucose for cellular metabolism Carbohydrate Metabolism • Glucose is catabolized in three pathways • Glycolysis • Krebs cycle • Electron transport chain Chemical energy (high-energy electrons) Chemical energy Glycolysis Glucose Cytosol Krebs cycle Pyruvic acid Mitochondrial cristae Via substrate-level phosphorylation 1 During glycolysis, each glucose molecule is broken down into two molecules of pyruvic acid in the cytosol. Electron transport chain and oxidative phosphorylation Mitochondrion 2 The pyruvic acid then enters the mitochondrial matrix, where the Krebs cycle decomposes it to CO2. During glycolysis and the Krebs cycle, small amounts of ATP are formed by substratelevel phosphorylation. Via oxidative phosphorylation 3 Energy-rich electrons picked up by coenzymes are transferred to the electron transport chain, built into the cristae membrane. The electron transport chain carries out oxidative phosphorylation, which accounts for most of the ATP generated by cellular respiration. Figure 24.5 Carbohydrate Metabolism • Glycolysis • • • • 10-step pathway Anaerobic Occurs in the cytosol Glucose 2 pyruvic acid molecules Carbohydrate Metabolism • Glycolysis • Final products • Net gain of 2 ATP • 2 pyruvic acid molecules • Enter aerobic pathways if O2 is readily available Figure 24.6 The three major phases of glycolysis. Glucose Glycolysis Krebs cycle Glycolysis takes place in the cytosol Electron transport chain and oxidative phosphorylation Carbon atom Phosphate Phase 1 Sugar Activation Glucose is activated by phosphorylation 2 ADP and converted to fructose-1, Fructose-1,66-bisphosphate bisphosphate Phase 2 Sugar Cleavage Fructose-1, 6-bisphosphate is cleaved into two 3-carbon Dihydroxyacetone fragments phosphate Glyceraldehyde 3-phosphate Phase 3 Sugar oxidation and formation 2 NAD+ of ATP 4 ADP The 3-carbon frag2 NADH+H+ ments are oxidized (by removal of hydrogen) and 4 ATP 2 Pyruvic acid molecules are formed 2 NADH+H+ 2 NAD+ 2 Lactic acid To Krebs cycle (aerobic pathway) Copyright © 2010 Pearson Education, Inc. Carbohydrate Metabolism • Krebs cycle • Occurs in mitochondrial matrix • Electron (H+) carriers are reduced • Fueled by pyruvic acid and fatty acids • Some amino acids can also form pyruvic acid • Also called citric acid cycle Carbohydrate Metabolism • Krebs cycle summary • Occurs in the presence of oxygen • Pyruvic acid molecules enter mitochondrion • Catabolized to acetyl CoA • Acetyl Co A citric acid • Each citric acid generates • 2 CO2 • 1 ATP • Electrons are transferred to coenzymes which fuel the electron transport system Figure 24.7 Simplified version of the Krebs (citric acid) cycle. Glycolysis Krebs cycle Cytosol Electron transport chain and oxidative phosphorylation Pyruvic acid from glycolysis Transitional phase Carbon atom Inorganic phosphate Coenzyme A Mitochondrion (matrix) NAD+ CO2 NADH+H+ Acetyl CoA Oxaloacetic acid NADH+H+ (pickup molecule) Citric acid (initial reactant) NAD+ Malic acid Isocitric acid NAD+ Krebs cycle CO2 NADH+H+ -Ketoglutaric acid Fumaric acid CO2 FADH2 Succinic acid FAD GTP ADP Copyright © 2010 Pearson Education, Inc. Succinyl-CoA GDP + NAD+ NADH+H+ Carbohydrate Metabolism • Electron transport chain • Cytochromes • Proteins bound to iron atoms on inner mitochondrial membrane • Electrons passed from cytochrome to cytochrome • Release energy during transfer Outer mitochondrial membrane Ribosome Mitochondrial DNA (a) Inner mitochondrial membrane Cristae Matrix (c) Enzymes (b) Copyright © 2010 Pearson Education, Inc. Figure 3.17 Carbohydrate Metabolism • Electron transport chain • Hydrogen atoms are split into H+ and electrons • Electrons are shuttled along the inner mitochondrial membrane, losing energy at each step • Released energy is used to pump H+ into the intermembrane space • Diffusion of H+ back through membrane is coupled to ATP production system Glycolysis Krebs cycle Electron transport chain and oxidative phosphorylation Intermembrane space Inner mitochondrial membrane 2 H+ + FADH2 NADH + (carrying from food) Mitochondrial matrix Copyright © 2010 Pearson Education, Inc. 1 2 ATP synthase FAD H+ NAD+ Electron Transport Chain Electrons are transferred from complex to complex and some of their energy is used to pump protons (H+) into the intermembrane space, creating a proton gradient. ADP + Chemiosmosis ATP synthesis is powered by the flow of H+ back across the inner mitochondrial membrane through ATP synthase. Figure 24.8 Carbohydrate Metabolism • Electron transport chain • One glucose molecule 32 - 34 ATP • Different cells have different totals due to various mechanisms present • Oxygen is final electron acceptor and has greatest affinity for hydrogen • Cyanide blocks terminal cytochrome which kills the cell Glycolysis Krebs cycle Electron transport chain and oxidative phosphorylation Intermembrane space Inner mitochondrial membrane 2 H+ + FADH2 NADH + (carrying from food) Mitochondrial matrix Copyright © 2010 Pearson Education, Inc. 1 2 ATP synthase FAD H+ NAD+ Electron Transport Chain Electrons are transferred from complex to complex and some of their energy is used to pump protons (H+) into the intermembrane space, creating a proton gradient. ADP + Chemiosmosis ATP synthesis is powered by the flow of H+ back across the inner mitochondrial membrane through ATP synthase. Figure 24.8 Cellular Respiration Cytosol Mitochondrion 2 NADH + H+ Electron shuttle across mitochondrial membrane Glycolysis Glucose Pyruvic acid 2 NADH + H+ 2 Acetyl CoA 6 NADH + H+ Krebs cycle (4 ATP–2 ATP used for activation energy) Net +2 ATP by substrate-level phosphorylation Electron transport chain and oxidative phosphorylation 10 NADH + H+ x 2.5 ATP 2 FADH2 x 1.5 ATP +2 ATP by substrate-level phosphorylation About 32 ATP Copyright © 2010 Pearson Education, Inc. 2 FADH2 + about 28 ATP by oxidative phosphorylation Maximum ATP yield per glucose Figure 24.12 Cellular Respiration • Oxidation of glucose C6H12O6 + 6O2 6H2O + 6CO2 + heat But heat isn’t useful so... C6H12O6 + 6O2 + 38 ADP + 38 P 6H2O + 6CO2 + 38 ATP + less heat Anaerobic Metabolism • Production of ATP in the absence of oxygen • Lactic acid fermentation glucose →→→→ 2 pyruvic acid → lactic acid Anaerobic Metabolism • Muscles during activity • At high levels of contractile activity: • • • • Bulging muscles compress blood vessels Oxygen delivery is impaired Pyruvic acid is converted into lactic acid Small amounts of ATP can be produced in the absence of oxygen (b) Anaerobic pathway Glycolysis and lactic acid formation Energy source: glucose Glucose (from glycogen breakdown or delivered from blood) Glycolysis in cytosol 2 O2 ATP Pyruvic acid net gain O2 Released to blood Lactic acid Oxygen use: None Products: 2 ATP per glucose, lactic acid Duration of energy provision: 60 seconds, or slightly more Figure 9.19b Anaerobic Metabolism • Lactic acid fermentation problems • Relatively small yield of ATP • May produce muscle pain • Liver can convert lactic acid into pyruvic acid • Process requires oxygen • Oxygen debt Efficiency of Aerobic Cellular Respiration • Calorie • Energy to raise the temperature of 1 gram of water by 1⁰C • 1,000 calories = 1 kcal • 1 mole (180 grams) of glucose releases 686 kcal • One mole ATP = 7 kcal • Glucose catabolism • 38 ATP = 278 kcal • 278/686 = 40% efficiency • 60% lost as heat • Most human made machines have about 10-30% efficiency Questions? • No homework this week! • Consider studying for the final…