Amino Acid Synthesis Lecture Notes PDF

College of pharmacy Stage Three Second semester Biosynthesis of the Nutritionally Nonessential Amino Acids Catabolism of Proteins & of Amino Acid Nitrogen Asst. Lecturer: Dr.Rithab Ibrahim The catabolism of...

College of pharmacy Stage Three Second semester Biosynthesis of the Nutritionally Nonessential Amino Acids Catabolism of Proteins & of Amino Acid Nitrogen Asst. Lecturer: Dr.Rithab Ibrahim The catabolism of the amino acids Involves the removal of α-amino groups, followed by the breakdown of the resulting carbon skeletons. These pathways converge to form seven intermediate products: 1- oxaloacetate, 2- pyruvate, 3- α-ketoglutarate, 4- fumarate, 5-succinyl coenzyme A(CoA), 6- acetyl CoA, 7- acetoacetate. These products directly enter the pathways of intermediary metabolism, resulting either in the synthesis of 1- glucose 2- lipid 3- production of energy through their oxidation to CO2 by the citric acid cycle. Amino acid metabolism Definition Nonessential amino acids Can be synthesized in sufficient amounts from the intermediates of metabolism or, as in the case of cysteine and tyrosine, from essential amino acids. Essential amino acids cannot be synthesized (or produced in sufficient amounts) by the body and, therefore, must be obtained from the diet in order for normal protein synthesis to occur. GLUCOGENIC AND KETOGENIC AMINO ACIDS Amino acids can be classified as glucogenic, ketogenic, or both based on which of the seven intermediates are produced during their catabolism A. Glucogenic amino acids: Amino acids whose catabolism yields pyruvate or one of the intermediates of the citric acid cycle are termed glucogenic. These intermediates are substrates for gluconeogenesis and, therefore, can give rise to the net formation of glucose in the liver and kidney. Classification of amino acids B. Ketogenic amino acids Amino acids whose catabolism yields either aceto acetate or one of its precursors (acetyl CoA or aceto acetyl CoA) are termed ketogenic Leucine and lysine are the only exclusively ketogenic amino acids found in proteins. BIOSYNTHESIS OF NONESSENTIAL AMINO ACIDS Nonessential amino acids are synthesized from intermediates of metabolism or, as in the case of tyrosine and cysteine, from the essential amino acids phenylalanine and methionine, respectively. A. Synthesis from α-keto acids Alanine, aspartate, and glutamate are synthesized by transfer of an amino group to theα-keto acids pyruvate, oxaloacetate, and α-keto - glutarate, respectively  B. Synthesis by amidation Glutamine: This amino acid, which contains an amide linkage with ammonia at the γ-carboxyl, is formed from glutamate by glutamine synthetase C. Proline Glutamate is converted to proline by cyclization and reduction reactions. D. Serine, Serine: This amino acid arises from 3-phosphoglycerate, an intermediate in glycolysis Catabolism of Amino Acid Nitrogen The presence of the α-amino group keeps amino acids safely locked away from oxidative breakdown. Removing the α-amino group is essential for producing energy from any amino acid, and is an obligatory step in the catabolism of all amino acids. A. Transamination: The first step in the catabolism of most amino acids is the transfer of their α-amino group to α-ketoglutarate B. Glutamate dehydrogenase: the oxidative deamination of amino acids In contrast to transamination reactions that transfer amino groups, oxidative deamination by glutamate dehydrogenase results in the liberation of the amino group as free ammonia (NH3) C. Transport of ammonia to the liver In most tissues, uses glutamine synthetase to combine ammonia (NH3) with glutamate to form glutamine—a nontoxic transport form of ammonia The glutamine is transported in the blood to the liver where it is cleaved by glutaminase to produce glutamate and free ammonia Transport of ammonia from peripheral tissues to the liver