Abstract—
Succinic semialdehyde dehydrogenase and NADPH‐dependent aldehyde reductase have been purified from ox brain by affinity chromatography on 5′ AMP–Sepharose and 2′5′ ADP–Sepharose respectively. Aldehyde reductase has also been purified using chromatography on Procion Red HE3B–Sepharose. The effects of the anticonvulsant drug sodium valproate were examined on these enzymes, and also on GABA‐aminotransferase partially purified from ox brain. Aldehyde reductase was inhibited by valproate in an uncompetitive manner with respect to aldehyde substrates (Ki= 38–85 μM). The inhibitions of succinic semialdehyde dehydrogenase and GABA aminotransferase were approx 2 orders of magnitude weaker, suggesting that aldehyde reductase may be an important site of action of anticonvulsant drugs.
The conversion of gamma-aminobutyrate (GABA) via succinic semialdehyde to gamma-hydroxybutyrate has been examined in rat brain homogenates. A number of anticonvulsants, including sodium valproate and phenobarbitone, inhibited this metabolic pathway. These results are interpreted in the light of the characteristics of aldehyde reductases known to reduce succinic semialdehyde.
particular route followed is dependent on the structure of the parent molecule (Tipton et al., 1977). The family of NADPH-The capacity to metabolize carbonyl-containing compounds is dependent aldehyde reductases (alcohol : NADP+ oxidowidespread among the animal, plant and microbial kingdoms. reductase, EC 1.1.1.2) primarily fulfil this reductive role. The This ability may be a general reflection of the need to remove classification of aldehyde reductases has proved complex, partly VOl. 9
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