NAD(P) adducts as protective agents against glutamate dehydrogenase inactivation by pyridoxal 5'-phosphate: a tool for the study of oxidized coenzyme activated state in enzymatic evolutive and abortive complexes.
Glutamate dehydrogenase is reversibly inhibited by the reaction of 1 mole of pyridoxal 5'-phosphate per mole of subunit of the enzyme polypeptide chain. We have shown that NAD(P) adducts as well as NMNH protect the glutamate dehydrogense against this reversible inactivation in the same way as reduced coenzymes. These data lead to the conclusion that it is the 1,4-dihydronicotinamide structure that is responsible for protecting the enzyme. NAD+ and NMN+ do not protect the enzyme, but in the presence of the oxidized substrate NAD+ became a good protecting agent whereas NMN+ remained ineffective. To explain the protection exerted by NAD+ in the presence of oxidized substrate, a transient activated form of the oxidized coenzyme with a 1,4-dihydronicotinamide structure and a positive charge on the C-4 atom is postulated.
D000818:Animals; D002417:Cattle; D055598:Chemical Phenomena; D002621:Chemistry; D005969:Glutamate Dehydrogenase / Q000037:antagonists & inhibitors*; D007656:Ketoglutaric Acids / Q000378:metabolism; D008297:Male; D009243:NAD / Q000378:metabolism*; D009249:NADP / Q000378:metabolism*; D009537:Nicotinamide Mononucleotide / Q000378:metabolism; D010071:Oxaloacetates / Q000378:metabolism; D011732:Pyridoxal Phosphate / Q000494:pharmacology*; D011773:Pyruvates / Q000378:metabolism; D019289:Pyruvic Acid; D013329:Structure-Activity Relationship; D013997:Time Factors
D007656:Ketoglutaric Acids; D010071:Oxaloacetates; D011773:Pyruvates; D009243:NAD; D009537:Nicotinamide Mononucleotide; D009249:NADP; D011732:Pyridoxal Phosphate; D019289:Pyruvic Acid; D005969:Glutamate Dehydrogenase