Transamination of GABA

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. 

GABA is metabolized by the enzyme GABA transaminase (GABA-T) to succinic semialdelhyde (Scheme 1). The first step in the transamination of GABA is the formation... 

SCHEME 2. Transamination of GABA. Reprinted from Reference 20, 1979, with permission from Pergamon Press Ltd, Headington Hill Hall, Oxford 0X3 OBW, UK... 

Inhibition of enzymatic breakdown of GABA GABA transaminase catalyzes pyridoxal-dependent transamination of GABA to succinic semialdehyde. The enzyme can be inhibited by a variety of compounds [e.g., y-vinyl GABA (Vigabatrin)]. 

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