Human brain aldehyde reductases: relationship to succinic semialdehyde reductase and aldose reductase.
Human brain contains multiple forms of aldehyde-reducing enzymes. One major form (AR3), as previously shown, has properties that indicate its identity with NADPH-dependent aldehyde reductase isolated from brain and other organs of various species; i.e., low molecular weight, use of NADPH as the preferred cofactor, and sensitivity to inhibition by barbiturates. A second form of aldehyde reductase ("SSA reductase") specifically reduces succinic semialdehyde (SSA) to produce gamma-hydroxybutyrate. This enzyme form has a higher molecular weight than AR3, and uses NADH as well as NADPH as cofactor. SSA reductase was not inhibited by pyrazole, oxalate, or barbiturates, and the only effective inhibitor found was the flavonoid quercetine. Although AR3 can also reduce SSA, the relative specificity of SSA reductase may enhance its in vivo role. A third form of human brain aldehyde reductase, AR2, appears to be comparable to aldose reductases characterized in several species, on the basis of its activity pattern with various sugar aldehydes and its response to characteristic inhibitors and activators, as well as kinetic parameters. This enzyme is also the most active in reducing the aldehyde derivatives of biogenic amines. These studies suggest that the various forms of human brain aldehyde reductases may have specific physiological functions.
D000429:Alcohol Oxidoreductases / Q000302:isolation & purification / Q000378:metabolism*; D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D001921:Brain / Q000201:enzymology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D006884:Hydroxybutyrate Dehydrogenase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005779:Immunodiffusion; D007700:Kinetics; D008970:Molecular Weight; D013379:Substrate Specificity; D013401:Sugar Alcohol Dehydrogenases / Q000378:metabolism*
D000429:Alcohol Oxidoreductases; D013401:Sugar Alcohol Dehydrogenases; C019642:alcohol dehydrogenase (NADP+); D000449:Aldehyde Reductase; D006884:Hydroxybutyrate Dehydrogenase; C019416:4-hydroxybutyrate dehydrogenase