Degradation and Synthesis of Amino Acids - PDF

DEGRADATION AND SYNTHESIS OF Dr Norsyahida Mohd Fauzi Lecturer in Biopharmacy and AMINO ACIDS Pharmacology Discipline, Member of Drug and Herbal Research...

DEGRADATION AND SYNTHESIS OF Dr Norsyahida Mohd Fauzi Lecturer in Biopharmacy and AMINO ACIDS Pharmacology Discipline, Member of Drug and Herbal Research Centre  OVERVIEW-AMINO ACID DEGRADATION AND SYNTHESIS - Catabolism (degradation) of amino acids: 1. Removal of α-amino groups. 2. Breakdown of carbon skeleton - Form seven intermediate products (oxaloacetate, pyruvate, α- ketoglutarate, fumarate, succinyl CoA, acetyl CoA and acetoacetate) 1. Glucogenesis 2. Energy - Anabolism (Synthesis) of amino acids: 1. Nonessential: synthesised from intermediates of metabolism 2. Essential: from diet - Genetic defects of pathways of aa metabolism  serious disease.  WHAT IS GLUCOGENIC AND KETOGENIC AMINO ACID? Glucogenic: a.a that catabolyzed to pyruvate or one of the intermediates of TCA cycle (substrate for gluconeogenesis). Ketogenic: a.a that catabolized to acetoacetate/acetyl CoA/acetoacetyl CoA Leucin and lysine are exclusively ketogenic. They are not substrate for gluconeogenesis. CATABOLISM OF THE CARBON SKELETONS OF AMINO ACIDS 1. oxaloacetate 7. 2. acetoacetate pyruvate Amino 3. α- acids ketoglutarate 6. acetyl CoA/ acetoaceyl 4. 5. succinyl CoA fumarate CoA AA TO OXALOACETATE AA TO PYRUVATE AA TO Α-KETOGLUTARATE  AA TO FUMARATE Deficiencies of enzymes of phenylalanine and tyrosine metabolism lead to the disease PKU, alkaptonuria and albinism AA TO SUCCINYL COA AA TO ACETYL COA AA TO ACETOACETATE CATABOLISM OF THE BRANCHED-CHAIN AMINO ACID Branched a.a: Isoleucine, Leucine and Valine (essential a.a) - Metabolized primarily in muscle, not liver. 3 steps - Transamination - Oxidative decarboxylation - Dehydrogenation ESSENTIAL VERSUS NONESSENTIAL AA  BIOSYNTHESIS OF NONESSENTIAL AA Synthesis from α-keto acids: - Serine: From 3- - Alanine (from pyruvate) phosphoglycerate - Aspartate (from oxaloacetate) (intermediate in glycolysis) - Glutamate (from α- - Glycine : From serine by ketoglutarate) serine - Catalyzed by aminotransferase hydroxymethyl transferase Synthesis from - Cystein: From homocystein Glutamate & L- serine- formed from essential aa - Proline Synthesis by amidation: - Glutamine (from glutamate Tyrosine: From phenylalanine by glutamine synthetase) by phenylalanine hydroxylase - formed from essential aa. - Asparagine (from - Nonessential in the aspartate by asparagine presence of adequate synthetase) phenylalanine FORMATION OF ALANINE, ASPARTATE AND GLUTAMATE Glutamate can also be synthesized by hydrolysis of glutamine catalyzed by glutaminase