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Chapter Outline 15.1 Metabolic Pathways, Energy, and Coupled Reactions 15.5 Gluconeogenesis 15.6 Glycogen Metabolism 15.2 Overview of Metabolism 15.3 Digestion 15.4 Glycolysis 15.7 Citric Acid Cycle 15.8 Electron Transport Chain and Oxidative Phosphorylation 15.9 Lipid Metabolism 15.10 Amino Acid Metabolism 1 • To discuss how living things manufacture or break down carbohydrates, lipids, or members of any other biochemical class of compounds it is necessary to talk in terms of groups of reactions called metabolic pathways. • The metabolic pathways can be: 1) linear – a continuous series of reactions in which the product of one reaction is the reactant in the next. 2) circular – a series of reactions where the final product is an initial reactant. 3) spiral – a series of repeated reactions is used to break down or build up a molecule. 2 15.1: Metabolic Pathways, Energy, and Coupled Reactions 3 Coupled Rxn: In a coupled reaction, a spontaneous reaction provides the energy needed to a nonspontaneous reaction. 1. Fructose 6-phosphate + Pi → fructose 1,6-biphosphate + H20 (∆G = 3.9 kcal/mol) 2. ATP + H2O → ADP + Pi (∆G = -7.3 kcal/mol) Overall: Fructose 6-phosphate + ATP → fructose 1,6-biphosphate + ADP (∆G = -3.4 kcal/mol) Is the coupled reaction spontaneous or nonspontaneous? 4 15.2: Metabolism, the sum of all reactions that take place in a living thing, can be divided into two parts: 1. Catabolism. During catabolism, compounds are broken down into smaller ones in processes that, usually, release energy. 2. Anabolism. Anabolism involves the biosynthesis of larger compounds from smaller ones in processes that, usually, require energy. 5 -ADP and ATP are key players in metabolism. -Energy released during catabolism is used to drive the formation of these two compounds. -Energy obtained by hydrolyzing ATP can, in turn, be used for anabolism or other energy requiring processes, such as muscle contraction. 6 7 8 Catabolism (break down of large molecules to small ones.) 9 Catabolism • Not all catabolic pathways take place in the same part of a cell. 1) Cytoplasm • glycolysis 2) Mitochondria • • • • • Fatty acid oxidation Amino acid catabolism Citric acid cycle Electron transport chain Oxidative phosphorylation 10 11 Anabolism • During anabolism, small molecules such as pyruvate, acetyl-CoA, and intermediates in the citric acid cycle are used to make fatty acids, monosaccharides, and amino acids for incorporation into lipids, polysaccharides, and proteins. 12 15.3: Digestion 13 Example of polysaccharide break down to monosaccharide. 14 Example of triglyceride and polypeptide break down. 15 15.4: Glycolysis 16 17 15.4: Glycolysis The net reaction for glycolysis is: Glucose + 2NAD+ + 2ADP + 2Pi → 2 pyruvate + 2NADH + 2ATP + energy Energy and Glycolysis: glucose + 2ADP + 2Pi → 2lactate + 2ATP ∆G = -29.4 kcal/mol spontaneous 18 • Metabolism can take pyruvate into a number of different directions. • In yeast, pyruvate undergoes alcoholic fermentation. • In this process pyruvate is split into acetaldehyde plus CO2, and acetaldehyde is reduced to ethanol. • These reactions serve to recycle NADH back into NAD+, allowing glycolysis to continue. 19 20 • In humans, pyruvate is reduced to lactate when conditions are anaerobic (O2 deficient) – This reaction converts NADH back into NAD+, allowing glycolysis to continue. – Once produced, lactate is sent in blood to the liver, where it can be used to make glucose. • Under aerobic conditions (O2 is in sufficient supply), pyruvate is converted into acetyl-CoA, the reactant for the first step in the citric acid cycle. – Glycolysis takes place in a cell’s cyctoplasm, but the formation of acetyl-CoA and the citric acid cycle take place inside the mitochondria. 21 15.7: Citric Acid Cycle 22 15.7: Citric Acid Cycle Overall Rxn: (occurs twice) Acetyl-CoA + 3NAD+ + FAD + GDP + Pi → 2CO2 + CoA + 3NADH + FADH2 + GTP ∆G = -11 kcal/mol 23 15.8: Electron Transport Chain and Oxidative Phosphorylation The electron transport chain is a group of proteins and other molecules embedded in the inner mitochondrial membrane. The electron transport chain and oxidative phosphorylation use the potential energy present in NADH and FADH2 to make ATP. 24 25 Summary of Glucose catabolism: 26 15.9: Lipid Metabolism 27 Four reactions in the b-oxidation of a fatty acid 28 b-oxidation Spiral of a fatty acid 29 Fatty Acid Catabolism • One common fate of fatty acids is their use as reactants in the formation of triglycerides, sphingolipids, and other lipids that contain fatty acid residues. • Their other important use is as a source of energy. • Fatty acid catabolism involves a spiral metabolic pathway, called the b oxidation spiral, where the same series of reactions is repeated on increasingly shorter reactants. 30 15.10: Amino Acid Metabolism • Removal of the amino group is an important part of amino acid catabolism. • The two reactions most often used to do this are: 1) Transamination is the transfer of an amino group from an amino acid to an -keto acid. These reactions are catalyzed by transaminase enzymes. 2) In oxidative deamination an amino group is replaced by a carbonyl (C=O) group. 31 32 33 34 Amino Acid Anabolism • Of the 20 amino acids used to synthesize proteins, humans can make only half. • The others, called essential amino acids, must be obtained in the diet. 35 36 15.5: Gluconeogenesis • • Gluconeogenesis, the pathway involved in making glucose from noncarbohydrate sources, such as amino acids, glycerol, and lactate, takes place mostly in the liver. One important role of this process is the conversion of lactate produced during anaerobic catabolism back into glucose, which is either transformed into glycogen or goes into the blood and is transported to other cells. 37 • In addition to recycling lactate, gluconeogenesis is a provider of glucose during fasting or in the early stages of starvation, in which glucose and glycogen (a source of glucose) have been depleted. • The supply of glucose is especially important to brain cells, which use only glucose to fuel metabolism, unlike other cells in the body which can also use lipids and proteins. 38 15.5: Gluconeogenesis 39 15.6: Glycogen Metabolism • Glycogen, a highly branched homopolysaccharide, is found mainly in liver and muscle cells. • This carbohydrate is a glucose storage molecule that, when necessary, can be quickly broken down to release glucose. • Glycogen is synthesized from or is broken down into glucose 6-phosphate. 40 15.6: Glycogen Metabolism 41