CHAPTER-VI PROTEIN METABOLISM TRANSAMINATION OF AMINO ACIDS Transaminases catalyze the transfer of -NH2 groups from the amino acids, onto alpha- ketoglutarate. Many different transaminases are known, and they are generally of broad specificity for amino acids (that is, one enzyme can accept as substrates two or more different amino acids). All have the same cofactor requirement - pyridoxal phosphate (vitamin B6). (Two amino acids can be directly deaminated: Serine and Threonine. They do not undergo this process of transamination.) Mechanism of transamination PLP plays a central role here in the interconversion of an amino acid and an alpha-keto acid. (1) Transaminase binds pyridoxal phosphate in a Schiff-base link to a Lysine residue of enzyme (the attachment is to the epsilon-amino group of the Lysine). This forms an "aldimine". (2) As a new substrate substrate enters the active site, its amino group displaces the -NH2 of active site Lysine. Then a new Schiff-base link is formed to the alpha-amino group of the substrate, as the active site Lysine moves aside. (3) There is an electronic rearrangement resulting in shifting the double bond to form a "ketimine". (4) This is followed by hydrolysis to release PMP and an alpha-keto acid. (5) PMP combines with alpha-ketoglutarate in a reversal of steps 1-4. The net result is transfer of an amino group to alpha-ketoglutarate, and release of glutamate, while regenerating the PLP- enzyme complex. DEAMINATION OF AMINO ACIDS Introduction: Deamination is also an oxidative reaction that occurs under aerobic conditions in all tissues but especially the liver. During oxidative deamination, an amino acid is converted into the corresponding keto acid by the removal of the amine functional group as ammonia and the amine functional group is replaced by the ketone group. The ammonia eventually goes into the urea cycle. Oxidative deamination occurs primarily on glutamic acid because glutamic acid was the end product of many transamination reactions. The glutamate dehydrogenase is allosterically controlled by ATP and ADP. ATP acts as an inhibitor whereas ADP is an activator. DECARBOXYATION OF AMINO ACIDS Decarboxylation is a chemical reaction that releases carbon dioxide (CO2). Usually, decarboxylation refers to a reaction of carboxylic acids, removing a carbon atom from a carbon chain. The reverse process, which is the first chemical step in photosynthesis, is called carbonation, the addition of CO2 to a compound. Enzymes that catalyze decarboxylations are called decarboxylases or, the more formal term, carboxy-lyases Urea Cycle The urea cycle (also known as the ornithine cycle) is a cycle of biochemical reactions occurring in many animals that produces urea ((NH2H )2CO) from ammonia (NH3). This cycle was the first metabolic cycle discovered (Hans Krebs and Kurt Henseleit, 1932), five years before the discovery of the TCA cycle. In mammals, the urea cycle takes place primarily in the liver, and to a lesser extent in the kidney The urea cycle consists of five reactions: two mitochondrial and three cytosolic. The cycle + − converts two amino groups, one from NH4 and one from Asp, and a carbon atom from HCO3 , to the relatively nontoxic excretion product urea at the cost of four "high-energy" phosphate bonds (3 ATP hydrolyzed to 2 ADP and one AMP). Ornithine is the carrier of these carbon and nitrogen atoms.. K.ANITA PRIYADHARSHINI LECTURER DEPT.OF PHARMACEUTICAL CHEMISTRY SRM COLLEGE OF PHARMACY .