Affinity modification of microsomal flavoproteins by NAD(P) 2',3'-dialdehydes.
NADPH-cytochrome P-450 reductase (FP1) and NADH-cytochrome b5 reductase (FP2) involved in the microsomal fraction of rat liver have been modified chemically by periodate-oxidized NADP+ and NAD+ (o-NAD(P]. Despite its low Ki values (approximately 30 microM) o-NADP is not covalently bound with FP1, although o-NAD with Ki greater than 100 microM chemically modifies FP1 by suppressing its activity. The protective effect of NADP+ against FP1 inactivation indicates that FP1 is modified in the NADP+ binding site. An active centre of FP2 is modified by o-NAD in the same manner as FP1 (NAD+ prevents FP2 from inactivation). FP2 is slightly inactivated when the concentration of o-NADP is one order of magnitude higher than that of o-NAD. As found, the o-NAD-modified microsomal FP1 inhibits the oxidation of cytochrome P-450 substrates (acetanilide and p-nitroanisole).
Slepneva
I A
IA
Institute of Chemical Kinetics and Combustion, Novosibirsk, USSR.
Weiner
L M
LM
D000345:Affinity Labels / Q000494:pharmacology*; D000447:Aldehydes / Q000494:pharmacology*; D000818:Animals; D001665:Binding Sites; D003579:Cytochrome Reductases / Q000037:antagonists & inhibitors*; D042966:Cytochrome-B(5) Reductase; D007700:Kinetics; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D009243:NAD / Q000494:pharmacology*; D009249:NADP / Q000494:pharmacology*; D009251:NADPH-Ferrihemoprotein Reductase / Q000037:antagonists & inhibitors*; D010084:Oxidation-Reduction; D051381:Rats; D011919:Rats, Inbred Strains
D000345:Affinity Labels; D000447:Aldehydes; D009243:NAD; D009249:NADP; D003579:Cytochrome Reductases; D042966:Cytochrome-B(5) Reductase; D009251:NADPH-Ferrihemoprotein Reductase