GABA transaminase

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 transaminase is a mitochondrial enzyme which, like GAD, requires pyridoxal phosphate as co-factor. It is present in both neurons and glia and while secondary to... 

Introduced initially for absence seizures, this drug is now known to be effective in and used to treat tonic lonic seizures and most types of epilepsy. It was found to inhibit GABA transaminase and so elevate GABA concentrations and inhibition. This is achieved, however, over a slower time-course than its anti-seizure effect, especially experimentally, which is now thought to be due to its phenytoin-like, use-dependent block of sodium channels. Since, unlike phenytoin, the full effect of valproate takes some weeks to develop, its slower effect on GABA metabolism and activity should not be ignored. 

Monoamine oxidase B Monoamine oxidase Thymidylate synthase GABA transaminase... 

Disorders of GABA Vitamin B6-dependent seizures Often an absence of succinic semialdehyde dehydrogenase Hypotonia, ataxia, mental retardation in older child. Increased urine 4-OH-butyric acid. Pyridoxine (B6-dependent disorder) Inhibitors of GABA transaminase... 

Of the many drugs that have been developed which modulate GABA function, the inhibitors of GABA transaminase have been shown to be effective anticonvulsants. These are derivatives of valproic acid that not only inhibit the metabolism of GABA but may also act as antagonists of the GABA autoreceptor and thereby enhance the release of the neurotransmitter. GABA-uptake inhibitors have also been developed (for example, derivatives... 

Valproic acid and its salts are a new group of antiepileptic drugs that differs from the known drugs both structurally and in terms of its mechanism of action. It is believed that it acts on the metabolism of the GABA system. Valproic acid has been shown to elevate the level of GABA in the brain by means of competitive inhibition of GABA transaminase and the dehydrogenase of succinic semialdehyde. 

They are different from vigabatrin (4) in that they are not inhibitors of GABA transaminase, and, in contrast to tiagabine (5), these molecules do not directly inhibit GABA reuptake (Bryans and Wustrow, 1999 Taylor, 1994). 

Vigabatrin is a new antiepileptic for use in epilepsy unresponsive to other therapy. It is an irreversible inhibitor of GABA-transaminase, the enzyme responsible for inactivation of the neurotransmitter GABA and it has shown efficacy against partial and secondarily generalized seizures. The principal unwanted effects are psychiatric disorders, including depression and psychosis, in a small number of patients. 

It is an inhibitor of GABA transaminase which degrades GABA. It suppresses maximal electroshock and kindled seizures and is used in partial seizure with or without generalization. 

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