GABA transamination

The optimal pH values for GAD and GABA-transaminase activities are around 5.8 and 8.9. Dnring withering (a kind of stress), the pH of cell cytoplast in tea leaves was decreased. Therefore, it favored the GAD but not GABA-transaminase activity. It resnlted in the block of GABA transamination and further GABA accumulation. 

It is well recognized that there is a rapid postmortal increase of GABA m the brain (Minard and Mushahwar, 1966). The increase is caused by GABA synthesis proceeding initially at the same rate postmortem as in vivo, and an almost complete inhibition of GABA catabolism by anoxia. The latter occurs because GABA transamination requires 2-oxoglutarate for transamination and oxidized NAD for the oxidation of succinic semialdehyde. 

Pyridoxamine phosphate serves as a coenzyme of transaminases, e.g., lysyl oxidase (collagen biosynthesis), serine hydroxymethyl transferase (Cl-metabolism), S-aminolevulinate synthase (porphyrin biosynthesis), glycogen phosphoiylase (mobilization of glycogen), aspartate aminotransferase (transamination), alanine aminotransferase (transamination), kynureninase (biosynthesis of niacin), glutamate decarboxylase (biosynthesis of GABA), tyrosine decarboxylase (biosynthesis of tyramine), serine dehydratase ((3-elimination), cystathionine 3-synthase (metabolism of methionine), and cystathionine y-lyase (y-elimination). 

Succinic semialdehyde (SSA) is synthesized in the mitochondria through transamination of y-aminobutyric acid (GABA) by GABA transaminase (GABA-T). Most of the SSA is oxidized by SSA dehydrogenase (SSA-DH) to form succinate, which is used for energy metabolism and results in the end products CO2 + H2O, which are expired. A small portion of SSA (<2%) is converted by SSA reductase (SSA-R) in the cytosol to GHB. GHB may also be oxidized back to SSA by GHB dehydrogenase (GHB-DH). 

GABA acts as an inhibitory transmitter in many different CNS pathways. It is subsequently destroyed by a transamination reaction (see Section 15.6) in which the amino group is transferred to 2-oxoglutaric acid, giving glutaric acid and succinic semialdehyde. This also requires PLP as a cofactor. Oxidation of the aldehyde group produces succinic acid, a Krebs cycle intermediate. 

GABA synthesis inhibitors act on the enzymes involved in the decarboxylation and transamination of GABA. Glutamic acid decarboxylase (GAD), the first enzyme in GABA biosynthesis, is inhibited easily by carbonyl reagents such as hydrazines [e.g., hydrazinopropionic acid (4.164) or isonicotinic acid hydrazide (4.165)], which trap pyridoxal, the essential cofactor of the enzyme. A more specific inhibitor is allylglycine (4.166). All of these compounds cause seizures and convulsions because they decrease the concentration of GABA. 

Central effects on blood pressure regulation as a result of decreased synthesis of brain GABA and serotonin (5-hydroxytryptamine). Glutamate decarboxylase activity in the nervous system is especially sensitive to vitamin Bg depletion, possibly as a result of mechanism-dependent inactivation by transamination. Although there is no evidence that aromatic amino acid decarboxylase activity is reduced in vitamin Bg deficiency, there is reduced formation of serotonin in the central nervous system. 

GABA-T utilizes pyridoxal as the cofactor in the transamination reaction (Fig. 12-7A). Pyridoxal 5-phosphate (Vitamin B6, the cofactor) forms a Schiff base with GABA s NH2 group. The adjacent C-H bond has its proton abstracted by the enzyme reprotonation results in the tautomeric Schiff base, which on hydrolysis affords succinic semialdehyde and pyridoxamine. The pyridoxamine then forms a Schiff base with the carbonyl of a-ketoglutarate, reversing the steps, whereby hydrolysis of the tautomeric base yields l-glutamic acid, and the pyridoxamine, which has given up its NH2 function, reverts to the cofactor aldehyde form to repeat the cycle. 

Glutamate in the brain and central nervous system can be converted to gamma amino butyric acid (GABA), which is catalyzed by glutamate decarboxylase. GABA is a neurotransmitter inhibitor compound that can be metabolized by transamination followed by oxidation. 

Glutamate is a central amino acid in general amino-acid metabolism. It plays a major role in transamination, ammonia production, formation of ornithine, proline, glutamine, and g-amino butyric acid (GABA). 

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