Amidination of amino groups of aldehyde reductase from human liver.
Amidination of human liver aldehyde reductase (alcohol:NADP+ oxidoreductase, EC 1.1.1.2) with monofunctional n-alkane methylimidates increased the enzymic activity by 10--30%, whereas analogous bifunctional imidoesters caused a loss of activity of about 80%. Both effects were prevented in the presence of the coenzyme NADPH or NADP+, but not of the substrate 4-nitrobenzaldehyde. Amidination increased the apparent Michaelis constant of both the coenzyme (up to 20-fold) and the substrate (about 5-fold). Bifunctional imidoesters with at least 4 carbon atoms between the functional groups (approx. 0.7 nm) crosslinked the enzyme intramolecularly. This reaction was retarded in the presence of the coenzyme, whereas 4-nitrobenzaldehyde had no effect. The results suggest the presence of reactive amino groups at the coenzyme binding site of aldehyde reductase.
D000429:Alcohol Oxidoreductases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000588:Amines; D001547:Benzaldehydes / Q000378:metabolism; D001665:Binding Sites; D004119:Dimethyl Adipimidate / Q000494:pharmacology; D004120:Dimethyl Suberimidate / Q000494:pharmacology; D006801:Humans; D007094:Imides / Q000494:pharmacology*; D008099:Liver / Q000201:enzymology*; D009249:NADP / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000588:Amines; D001547:Benzaldehydes; D007094:Imides; D004119:Dimethyl Adipimidate; D004120:Dimethyl Suberimidate; D009249:NADP; D000429:Alcohol Oxidoreductases