Chemistry: An Introduction to General, Organic, and Biological Chemistry, Eleventh Edition Copyright © 2012 by Pearson Education, Inc. Chapter 18 Metabolic Pathways and Energy Production 18.8 Degradation of Amino Acids 1

Chemistry: An Introduction to General, Organic, and Biological Chemistry, Eleventh Edition Copyright © 2012 by Pearson Education, Inc. Degradation of Amino Acids Proteins provide energy when carbohydrate and lipid resources are not available carbon atoms to be used in the citric acid cycle carbon atoms to be used in synthesis of fatty acids, ketone bodies, and glucose 2

Chemistry: An Introduction to General, Organic, and Biological Chemistry, Eleventh Edition Copyright © 2012 by Pearson Education, Inc. Transamination In transamination, amino acids are degraded in the liver an amino group is transferred from an amino acid to an  - keto acid, usually  -ketoglutarate a new amino acid and  -keto acid are formed when alanine combines with  -ketoglutarate, pyruvate and glutamate are produced 3

Chemistry: An Introduction to General, Organic, and Biological Chemistry, Eleventh Edition Copyright © 2012 by Pearson Education, Inc. A Transamination Reaction NH 3 + O | || CH 3 —CH—COO – + – OOC—C—CH 2 —CH 2 —COO – Alanine  -Ketoglutarate O NH 3 + || | CH 3 —C—COO – + – OOC—CH—CH 2 —CH 2 —COO – Pyruvate Glutamate (new  -ketoacid) (new amino acid) 4 Alanine transaminase

Chemistry: An Introduction to General, Organic, and Biological Chemistry, Eleventh Edition Copyright © 2012 by Pearson Education, Inc. Oxidative Deamination Oxidative deamination removes the ammonium group (−NH 3 + ) from glutamate as NH 4 + regenerates  -ketoglutarate for transamination NH 3 + Glutamate │ dehydrogenase – OOC—CH—CH 2 —CH 2 —COO – + NAD + + H 2 O Glutamate O || – OOC—C—CH 2 —CH 2 —COO – + NH NADH  -Ketoglutarate 5

Chemistry: An Introduction to General, Organic, and Biological Chemistry, Eleventh Edition Copyright © 2012 by Pearson Education, Inc. Learning Check Write the structures and names of the products for the transamination of  -ketoglutarate by aspartate. NH 3 + | – OOC—CH—CH 2 —COO – Aspartate + O || – OOC—C—CH 2 —CH 2 —COO –  -Ketoglutarate 6

Chemistry: An Introduction to General, Organic, and Biological Chemistry, Eleventh Edition Copyright © 2012 by Pearson Education, Inc. Solution Write the structures and names of the products for the transamination of  -ketoglutarate by aspartate. O | – OOC—C—CH 2 —COO – Oxaloacetate + NH 3 + | – OOC—CH—CH 2 —CH 2 —COO – Glutamate 7

Chemistry: An Introduction to General, Organic, and Biological Chemistry, Eleventh Edition Copyright © 2012 by Pearson Education, Inc. Urea Cycle The urea cycle removes toxic ammonium ions from amino acid degradation converts ammonium ions to urea in the liver O + || 2NH 4 + CO 2 H 2 N—C—NH 2 Ammonium ions Urea produces 25–30 g of urea daily for urine formation in the kidneys 8

Chemistry: An Introduction to General, Organic, and Biological Chemistry, Eleventh Edition Copyright © 2012 by Pearson Education, Inc. ATP Energy from Amino Acids Carbon skeletons of amino acids form intermediates of the citric acid cycle produce energy enter the citric acid cycle at different places depending on the amino acid Three-carbon skeletons: alanine, serine, and cysteine pyruvate Four-carbon skeletons: aspartate, asparagine oxaloacetate Five-carbon skeletons: glutamine, glutamate, proline, arginine, histidine glutamate 9

Chemistry: An Introduction to General, Organic, and Biological Chemistry, Eleventh Edition Copyright © 2012 by Pearson Education, Inc. Intermediates of the Citric Acid Cycle from Amino Acids 10

Chemistry: An Introduction to General, Organic, and Biological Chemistry, Eleventh Edition Copyright © 2012 by Pearson Education, Inc. Learning Check Match each the intermediate with the amino acid that provides its carbon skeleton: pyruvate, fumarate, or  - ketoglutarate. A. cysteine B. glutamine C. aspartate D. serine 11

Chemistry: An Introduction to General, Organic, and Biological Chemistry, Eleventh Edition Copyright © 2012 by Pearson Education, Inc. Solution Match each the intermediate with the amino acid that provides its carbon skeleton: pyruvate, fumarate, or  - ketoglutarate. A. cysteinepyruvate B. glutamine  -ketoglutarate C. aspartatefumarate D. serinepyruvate 12

Chemistry: An Introduction to General, Organic, and Biological Chemistry, Eleventh Edition Copyright © 2012 by Pearson Education, Inc. Overview of Metabolism In metabolism, catabolic pathways degrade large molecules anabolic pathways synthesize molecules branch points determine which compounds are degraded to acetyl CoA to meet energy needs or converted to glycogen for storage excess glucose is converted to body fat fatty acids and amino acids are used for energy when carbohydrates are not available some amino acids are produced by transamination 13

Chemistry: An Introduction to General, Organic, and Biological Chemistry, Eleventh Edition Copyright © 2012 by Pearson Education, Inc. 14 Overview of Metabolism

Chemistry: An Introduction to General, Organic, and Biological Chemistry, Eleventh Edition Copyright © 2012 by Pearson Education, Inc. Metabolic Pathways Concept Map 15