Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings  High-energy phosphate groups are transferred directly from phosphorylated substrates to ADP  ATP is synthesized via substrate-level phosphorylation in glycolysis and the Krebs cycle Figure 24.4a Mechanisms of ATP Synthesis: Substrate-Level Phosphorylation

Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Stages of Metabolism Figure 24.3

Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Carbohydrate Metabolism  Since all carbohydrates are transformed into glucose, it is essentially glucose metabolism  Oxidation of glucose is shown by the overall reaction: C 6 H 12 O 6 + 6O 2  6H 2 O + 6CO ATP + heat  Glucose is catabolized in three pathways  Glycolysis  Krebs cycle  The electron transport chain and oxidative phosphorylation

Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Carbohydrate Catabolism Figure 24.5

Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Glycolysis  A three-phase pathway in which:  Glucose is oxidized into pyruvic acid  NAD + is reduced to NADH + H +  ATP is synthesized by substrate-level phosphorylation  Pyruvic acid:  Moves on to the Krebs cycle in an aerobic pathway  Is reduced to lactic acid in an anaerobic environment

Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Glycolysis Figure 24.6

Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Glycolysis  The final products are:  Two pyruvic acid molecules  Two NADH + H + molecules (reduced NAD + )  A net gain of two ATP molecules

Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Krebs Cycle: Preparatory Step  Occurs in the mitochondrial matrix and is fueled by pyruvic acid

Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Krebs Cycle: Preparatory Step  Pyruvic acid is converted to acetyl CoA in three main steps:  Decarboxylation  Carbon is removed from pyruvic acid  Carbon dioxide is released

Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Krebs Cycle: Preparatory Step  Oxidation  Hydrogen atoms are removed from pyruvic acid  NAD + is reduced to NADH + H +  Formation of acetyl CoA – the resulting acetic acid is combined with coenzyme A, a sulfur-containing coenzyme, to form acetyl CoA

Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Krebs Cycle  An eight-step cycle in which each acetic acid is decarboxylated and oxidized, generating:  Three molecules of NADH + H +  One molecule of FADH 2  Two molecules of CO 2  One molecule of ATP  For each molecule of glucose entering glycolysis, two molecules of acetyl CoA enter the Krebs cycle

Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Krebs Cycle Figure 24.7

Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Electron Transport Chain  Food (glucose) is oxidized and the released hydrogens:  Are transported by coenzymes NADH and FADH 2  Enter a chain of proteins bound to metal atoms (cofactors)  Combine with molecular oxygen to form water  Release energy  The energy released is harnessed to attach inorganic phosphate groups (P i ) to ADP, making ATP by oxidative phosphorylation

Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings 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-c 1  Cytochrome oxidase (a-a 3 )  The electrons are shuttled from one acceptor to the next

Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Mechanism of Oxidative Phosphorylation  Electrons are delivered to oxygen, forming oxygen ions  Oxygen ions attract H + to form water  H + pumped to the intermembrane space:  Diffuses back to the matrix via ATP synthase  Releases energy to make ATP InterActive Physiology ® : Muscular System: Muscular Metabolism PLAY

Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Mechanism of Oxidative Phosphorylation Figure 24.8

Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Electronic Energy Gradient  The transfer of energy from NADH + H + and FADH 2 to oxygen releases large amounts of energy  This energy is released in a stepwise manner through the electron transport chain

Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Electronic Energy Gradient  The electrochemical proton gradient across the inner membrane:  Creates a pH gradient  Generates a voltage gradient  These gradients cause H + to flow back into the matrix via ATP synthase Electron Transport PLAY

Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Electronic Energy Gradient Figure 24.9

Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings ATP Synthase  The enzyme consists of three parts: a rotor, a knob, and a rod  Current created by H + causes the rotor and rod to rotate  This rotation activates catalytic sites in the knob where ADP and P i are combined to make ATP

Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Structure of ATP Synthase Figure 24.10

Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Summary of ATP Production Figure 24.11

Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Glycogenesis and Glycogenolysis  Glycogenesis – formation of glycogen when glucose supplies exceed cellular need for ATP synthesis  Glycogenolysis – breakdown of glycogen in response to low blood glucose Figure 24.12

Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Gluconeogenesis  The process of forming sugar from noncarbohydrate molecules  Takes place mainly in the liver  Protects the body, especially the brain, from the damaging effects of hypoglycemia by ensuring ATP synthesis can continue

Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings 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  Only neutral fats are routinely oxidized for energy  Catabolism of fats involves two separate pathways  Glycerol pathway  Fatty acids pathway

Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Lipid Metabolism  Glycerol is converted to glyceraldehyde phosphate  Glyceraldehyde is ultimately converted into acetyl CoA  Acetyl CoA enters the Krebs cycle  Fatty acids undergo beta oxidation which produces:  Two-carbon acetic acid fragments, which enter the Krebs cycle  Reduced coenzymes, which enter the electron transport chain

Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Lipid Metabolism Figure 24.13

Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings 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

Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings 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)

Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Lipogenesis and Lipolysis Figure 24.14

Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings  Phospholipids are important components of myelin and cell membranes Lipid Metabolism: Synthesis of Structural Materials

Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings  The liver:  Synthesizes lipoproteins for transport of cholesterol and fats  Makes tissue factor, a clotting factor  Synthesizes cholesterol for acetyl CoA  Uses cholesterol to form bile salts  Certain endocrine organs use cholesterol to synthesize steroid hormones Lipid Metabolism: Synthesis of Structural Materials

Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings 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

Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Protein Metabolism  Deaminated amino acids are converted into:  Pyruvic acid  One of the keto acid intermediates of the Krebs cycle  These events occur as transamination, oxidative deamination, and keto acid modification