Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.6.1.19 (GABA transaminase)
 808 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Valproate, one of the major antiepileptic drugs used today, has besides its wide use in both generalized and partial epilepsies, several new approved indications including the treatment of bipolar disorders, neuropathic pain, and as a migraine prophylaxis. This wide spectrum of activities is reflected by several different mechanisms of action, which are discussed in this review. With regard to the antiepileptic effect of VPA, a special emphasis is put on the effect on the GABAergic system and the effect on enzymes like succinate semialdehyde dehydrogenase (SSA-DH), GABA transaminase (GABA-T), and alpha-ketoglutarate dehydrogenase, related to the tricarboxylic acid (TCA) cycle and thereby cerebral metabolism. In vitro studies have shown that VPA is a potent inhibitor of SSA-DH. In brain homogenates, GABA-T is inhibited at high concentrations only. Besides affecting the GABA-shunt, VPA might also inhibit the TCA cycle at the alpha-ketoglutarate dehydrogenase step. The effect of VPA on excitatory neurotransmission and on excitatory membranes are mechanisms likely to be responsible for the 'mood-stabilizing' effect as well as in the treatment of migraine. GABA-mediated responses may be involved in neuropathic pain. But still there are many aspects of the mechanisms of action of VPA that remain unknown.
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PMID:Mechanisms of action of valproate: a commentatory. 1081 95

We have studied the activities of the GABA metabolizing enzymes-GABA aminotransferase (GABA-AT), succinic semialdehyde dehydrogenase (SSA-DH) and SSA reductase (SSA-R) and the levels of GABA, glutamine and glutamate in rats preferring water (WP) or ethanol (EP) after 6 months of ethanol consumption and 12 hours to 7 days after withdrawal. We showed decreased GABA levels in the brain stem, decreased GABA-AT activity in the hemispheres and brain stem, and enhanced GABA-AT activity in the striatum of EP rats compared with the control or WP animals following chronic consumption of ethanol. We found decreased activity of SSA-R and SSA-DH in the hemispheres and brain stems of alcohol-treated rats compared to the control rats. Withdrawal (0.5-7 days) induced numerous profound changes in GABA metabolism.
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PMID:Brain GABA metabolism after chronic ethanol consumption and withdrawal in rats. 2673 41