Valproate inhibits which enzyme involved in GABA metabolism, thereby contributing to its anticonvulsant action?
- A GABA transaminase (GABA-T), increasing synaptic GABA availability ✓
- B Glutamic acid decarboxylase, reducing glutamate conversion
- C Monoamine oxidase, preventing GABA degradation
- D Succinic semialdehyde dehydrogenase, causing GABA accumulation
Correct answer: A. GABA transaminase (GABA-T), increasing synaptic GABA availability
Explanation
Valproate's GABA-enhancing mechanism includes inhibition of GABA transaminase (GABA-T), the pyridoxal phosphate-dependent enzyme that converts GABA to succinic semialdehyde, thereby reducing GABA catabolism. Valproate also inhibits succinic semialdehyde dehydrogenase (option D describes this as GABA accumulation but GABA-T is the primary step). Additionally, valproate enhances GABA synthesis by upregulating glutamic acid decarboxylase. Its broad-spectrum efficacy also involves sodium channel blockade and inhibition of T-type calcium channels in the thalamus.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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