Studies of covalent adducts of NAD(P) and enolizable ketones as specific glutamate dehydrogenase inhibitors.
Structural analogues of the reduced coenzymes, NADH or NADPH, of dehydrogenases are prepared by addition of carbonyl compounds including: pyruvate, alpha ketoglutarate, oxaloacetate, butyraldehyde, acetaldehyde and acetone, to the oxidized coenzymes NAD(P). Some of the adducts obtained are specific inhibitors of the glutamate dehydrogenase. The specificity is related to the carbonyl compound used. The high selectivity of the dehydrogenases for adducts is evidenced by inhibition studies of NAD(P)-pyruvate and NAD(P)-alpha ketoglutarate adducts on both activities of glutamate dehydrogenase. The inhibitions are competitive with the reduced coenzymes and the oxidized substrates: adducts could be considered as structures closely related to the ternary complexes of the dehydrogenase.
D000818:Animals; D002417:Cattle; D004305:Dose-Response Relationship, Drug; D005969:Glutamate Dehydrogenase / Q000037:antagonists & inhibitors*; D007700:Kinetics; D008099:Liver / Q000201:enzymology; D009243:NAD / Q000008:administration & dosage / Q000031:analogs & derivatives*; D009249:NADP / Q000008:administration & dosage / Q000031:analogs & derivatives*; D010084:Oxidation-Reduction; D013329:Structure-Activity Relationship
D009243:NAD; D009249:NADP; D005969:Glutamate Dehydrogenase