 | ||
Most amino acids are deaminated by transamination, a chemical reaction that transfers an amino group to a ketoacid to form new amino acids. This is one of the major degradation pathways which convert essential amino acids to nonessential amino acids (amino acids that can be synthesized de novo by the organism).
Contents
Transamination in biochemistry is accomplished by enzymes called transaminases or aminotransferases. α-ketoglutarate acts as the predominant aminogroup acceptor and produces glutamate as the new amino acid.
Aminoacid + α-ketoglutarate ↔ α-keto acid + GlutamateGlutamate's amino group, in turn, is transferred to oxaloacetate in a second transamination reaction yielding aspartate.
Glutamate + oxaloacetate ↔ α-ketoglutarate + aspartateMechanism of Action
Transamination catalyzed by aminotransferase occurs in two stages. In the first step, the α amino group of an aminoacid is transferred to the enzyme, producing the corresponding α-keto acid and the aminated enzyme. During the second stage, the amino group is transferred to the keto acid acceptor, forming the amino acid product while regenerating the enzyme. The chirality of an amino acid is determined during transamination. For the reaction to complete, aminotransferases require participation of aldehyde containing coenzyme, pyridoxyl-5'-phosphate (PLP), a derivative of Pyridoxine (Vitamin B6). The amino group is accommodated by conversion of this coenzyme to pyridoxamine-5'-phosphate (PMP). PLP is covalently attached to the enzyme via a Schiff Base linkage formed by the condensation of its aldehyde group with the ε-amino group of an enzymatic Lys residue. The Schiff base, which is conjugated to the enzymes pyridinium ring is the focus of the coenzyme activity.
The product of transamination reactions depend on the availability of α-keto acids. The products usually are either alanine, aspartate or glutamate, since their corresponding alpha-keto acids are produced through metabolism of fuels. Being a major degradative aminoacid pathway, lysine proline and threonine are the only three amino acids that do not always undergo transamination and rather use respective dehydrogenase. Alternative Mechanism A second type of transamination reaction can be described as a nucleophilic substitution of one amine or amide anion on an amine or ammonium salt. For example, the attack of a primary amine by a primary amide anion can be used to prepare secondary amines: RNH2 + R'NH− → RR'NH + NH2− Symmetric secondary amines can be prepared using Raney nickel (2RNH2 → R2NH + NH3). And finally, quaternary ammonium salts can be dealkylated using ethanolamine: R4N+ + NH2CH2CH2OH → R3N + RN+H2CH2CH2OH Aminonaphthalenes also undergo transaminations.[2]Types of aminotransferase
Transamination is mediated by several different aminotransferase enzymes. These may be specific for individual amino acids, or they may be able to process a group of chemically similar ones. The latter applies to the group of the branched-chain amino acids, which comprises leucine, isoleucine, and valine. The two common types of aminotransferases are Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST).