Identification of Pig Brain Aldehyde Reductases with the High‐Km Aldehyde Reductase, the Low‐Km Aldehyde Reductase and Aldose Reductase, Carbonyl Reductase, and Succinic Semialdehyde Reductase

Abstract

Four NADPH-dependent aldehyde reductases (ALR) isolated from pig brain were characterized with respect to substrate specificity, inhibition by drugs and immunological criteria. The major enzyme, ALR1, is identical in these respects with the high-Km aldehyde reductase, glucuronate reductase and tissue-specific, e.g., pig kidney aldehyde reductase. A 2nd enzyme, ALR2, is identical with the low-Km aldehyde reductase and aldose reductase. The 3rd enzyme, ALR3, is carbonyl reductase and has several features in common with prostaglandin-9-ketoreductase and xenobiotic ketoreductase. The 4th enzyme, unlike the other 3 which are monomeric is a dimeric succinic semialdehyde redcutase. All 4 of these enzymes are capable of reducing aldehydes derived from the biogenic amines. From a consideration of their substrate specificities and the relevant Km and Vmax values, it is likely that it is ALR2 which plays a primary role in biogenic aldehyde metabolism. Both ALR1 and ALR2 may be involved in the reduction of isocorticosteroids. Despite its capacity to reduce ketones, ALR3 is primarily an aldehyde reductase, but clues as to its physiological role in brain cannot be discerned from its substrate specificity. The capacity of succinic semialdehyde reductase to reduce succinic semialdehyde better than any othe substrate shows that this reductase is aptly named and suggests that its primary role is the maintenance in brain of physiological levels of .gamma.-hydroxybutyrate.