© 2003 Thomson Learning, Inc. All rights reserved General, Organic, and Biochemistry, 7e Bettelheim, Brown, and March

© 2003 Thomson Learning, Inc. All rights reserved Chapter 27 Specific Catabolic Pathways: Carbohydrate, Lipid, and Protein Metabolism

© 2003 Thomson Learning, Inc. All rights reserved Glycolysis Glycolysis: Glycolysis: a series of 10 enzyme-catalyzed reactions by which glucose is oxidized to two molecules of pyruvate there is net conversion of 2ADP to 2ATP

© 2003 Thomson Learning, Inc. All rights reserved Glycolysis - Rexn 1 reaction 1: reaction 1: phosphorylation of  -D-glucose

© 2003 Thomson Learning, Inc. All rights reserved Glycolysis - Rexn 2 reaction 2: reaction 2: isomerization of glucose 6-phosphate to fructose 6-phosphate

© 2003 Thomson Learning, Inc. All rights reserved Glycolysis - Rexn 2 this isomerization is most easily seen by considering the open-chain forms of each monosaccharide; it is one keto-enol tautomerism followed by another

© 2003 Thomson Learning, Inc. All rights reserved Glycolysis - Rexn 3 reaction 3: reaction 3: phosphorylation of fructose 6- phosphate

© 2003 Thomson Learning, Inc. All rights reserved Glycolysis - Rexn 4 reaction 4: reaction 4: cleavage of fructose 1,6-bisphosphate to two triose phosphates

© 2003 Thomson Learning, Inc. All rights reserved Glycolysis - Rexn 5 reaction 5: reaction 5: isomerization of triose phosphates catalyzed by phosphotriose isomerase reaction involves two successive keto-enol tautomerizations only the D enantiomer of glyceraldehyde 3-phosphate is formed

© 2003 Thomson Learning, Inc. All rights reserved Glycolysis - Rexn 6 Reaction 6: Reaction 6: oxidation of the -CHO group of D- glyceraldehyde 3-phosphate the product contains a phosphate ester and a high- energy mixed carboxylic-phosphoric anhydride

© 2003 Thomson Learning, Inc. All rights reserved Glycolysis - Rexn 7 Reaction 7: Reaction 7: transfer of a phosphate group from 1,3-bisphosphoglycerate to ADP

© 2003 Thomson Learning, Inc. All rights reserved Glycolysis - Rexn 8 & 9 Reaction 8: Reaction 8: isomerization of 3-phosphoglycerate to 2-phosphoglycerate Reaction 9: Reaction 9: dehydration of 2-phosphoglycerate

© 2003 Thomson Learning, Inc. All rights reserved Glycolysis - Rexn 10 Reaction 10 Reaction 10: phosphate transfer to ADP

© 2003 Thomson Learning, Inc. All rights reserved Glycolysis Summing these 10 reactions gives the net equation for glycolysis

© 2003 Thomson Learning, Inc. All rights reserved Reactions of Pyruvate Pyruvate is most commonly metabolized in one of three ways, depending on the type of organism and the presence or absence of O 2

© 2003 Thomson Learning, Inc. All rights reserved Reactions of Pyruvate A key to understanding the biochemical logic behind two of these reactions of pyruvate is to recognize that glycolysis needs a continuing supply of NAD + if no oxygen is present to reoxidize NADH to NAD +, then another way must be found to reoxidize it

© 2003 Thomson Learning, Inc. All rights reserved Pyruvate to Lactate in vertebrates under anaerobic conditions, the most important pathway for the regeneration of NAD + is reduction of pyruvate to lactate lactate dehydrogenase (LDH) is a tetrameric isoenzyme consisting of H and M subunits; H 4 predominates in heart muscle, and M 4 in skeletal muscle

© 2003 Thomson Learning, Inc. All rights reserved Pyruvate to Lactate while reduction to lactate allows glycolysis to continue, it increases the concentration of lactate and also of H + in muscle tissue when blood lactate reaches about 0.4 mg/100 mL, muscle tissue becomes almost completely exhausted

© 2003 Thomson Learning, Inc. All rights reserved Pyruvate to Ethanol Yeasts and several other organisms regenerate NAD + by this two-step pathway decarboxylation of pyruvate to acetaldehyde reduction of acetaldehyde to ethanol

© 2003 Thomson Learning, Inc. All rights reserved Pyruvate to Acetyl-CoA under aerobic conditions, pyruvate undergoes oxidative decarboxylation the carboxylate group is converted to CO 2 the remaining two carbons are converted to the acetyl group of acetyl CoA

© 2003 Thomson Learning, Inc. All rights reserved Energy Yield of Glycolysis

© 2003 Thomson Learning, Inc. All rights reserved Catabolism of Glycerol Glycerol enters glycolysis via dihydroxyacetone phosphate

© 2003 Thomson Learning, Inc. All rights reserved Fatty Acids and Energy Fatty acids in triglycerides are the principal storage form of energy for most organisms hydrocarbon chains are a highly reduced form of carbon the energy yield per gram of fatty acid oxidized is greater than that per gram of carbohydrate oxidized

© 2003 Thomson Learning, Inc. All rights reserved  -Oxidation  -Oxidation:  -Oxidation: a series of five enzyme-catalyzed reactions that cleaves carbon atoms two at a time from the carboxyl end of a fatty acid Reaction 1:Reaction 1: the fatty acid is activated by conversion to an acyl CoA; activation is equivalent to the hydrolysis of two high-energy phosphate anhydrides

© 2003 Thomson Learning, Inc. All rights reserved  -Oxidation Reaction 2:Reaction 2: oxidation of the ,  carbon-carbon single bond to a carbon-carbon double bond

© 2003 Thomson Learning, Inc. All rights reserved  -Oxidation Reaction 3:Reaction 3: hydration of the double bond Reaction 4:Reaction 4: oxidation of the  alcohol to a ketone

© 2003 Thomson Learning, Inc. All rights reserved  -Oxidation Reaction 5:Reaction 5: cleavage of the carbon chain by a molecule of CoA-SH

© 2003 Thomson Learning, Inc. All rights reserved  -Oxidation this series of reactions is then repeated on the shortened fatty acyl chain and continues until the entire fatty acid chain is degraded to acetyl CoA  -oxidation of unsaturated fatty acids proceeds in the same way, with an extra step that isomerizes the cis double bond to a trans double bond

© 2003 Thomson Learning, Inc. All rights reserved Energy Yield from  -Oxidation Yield of ATP per mole of stearic acid (C 18 )

© 2003 Thomson Learning, Inc. All rights reserved Ketone Bodies Ketone bodies Ketone bodies: acetone,  -hydroxybutyrate, and acetoacetate formed principally in liver mitochondria can be used as a fuel in most tissues and organs Formation occurs when the amount of acetyl CoA produced is excessive compared to the amount of oxaloacetate available to react with it intake high in lipids and low in carbohydrates diabetes not suitably controlled starvation

© 2003 Thomson Learning, Inc. All rights reserved Ketone Bodies

© 2003 Thomson Learning, Inc. All rights reserved Protein Catabolism

© 2003 Thomson Learning, Inc. All rights reserved Nitrogen of Amino Acids transamination -NH 2 groups move freely by transamination pyridoxal phosphate (Section18.7B) forms an imine (a C=N group) with the  -amino group of an amino acid rearrangement gives an isomeric imine hydrolysis of the isomeric imine gives an  -ketoacid and pyridoxamine

© 2003 Thomson Learning, Inc. All rights reserved Nitrogen of Amino Acids nitrogens to be excreted are collected in glutamate, which is oxidized to  -ketoglutarate and NH 4 + NH 4 + then enters the urea cycle

© 2003 Thomson Learning, Inc. All rights reserved The Urea Cycle - Overview Urea cycle: Urea cycle: a cyclic pathway that produces urea from CO 2 and NH 4 +

© 2003 Thomson Learning, Inc. All rights reserved The Urea Cycle

© 2003 Thomson Learning, Inc. All rights reserved The Urea Cycle

© 2003 Thomson Learning, Inc. All rights reserved Amino Acid Catabolism The breakdown of amino acid carbon skeletons follows two pathways glucogenic amino acids:glucogenic amino acids: ones whose carbon skeletons are degraded to pyruvate or oxaloacetate, both of which may then be converted to glucose by gluconeogenesis ketogenic amino acids:ketogenic amino acids: ones whose carbon skeletons are degraded to acetyl CoA or acetoacetyl CoA, both of which may then be converted to ketone bodies

© 2003 Thomson Learning, Inc. All rights reserved Amino Acid Catabolism

© 2003 Thomson Learning, Inc. All rights reserved Heme Catabolism When red blood cells are destroyed globin is hydrolyzed to amino acids iron is preserved in ferritin, an iron-carrying protein, and reused heme is converted to bilirubin bilirubin enters the liver via the bloodstream and is then transferred to the gallbladder where it is stored in the bile and finally excreted in the feces

© 2003 Thomson Learning, Inc. All rights reserved End Chapter 27 Catabolic Pathways