Suggested mechanism for the modulation of the activity of NAD(P)H:quinone acceptor oxidoreductase (DT-diaphorase) by menadione: interpretation of the effect of menadione on 5'-[p-(Fluorosulfonyl)benzoyl]adenosine labeling of rat liver NAD(P)H:quinone acceptor oxidoreductase.
5'-[p-(Fluorosulfonyl)benzoyl]adenosine (5'FSBA) was previously shown to be an active site-directed affinity label of rat liver NAD(P)H:quinone acceptor oxidoreductase [Mol. Pharmacol. 35:818-822 (1989)]. Our recent study revealed that menadione, the substrate of this quinone reductase, had a magnifying effect on inactivation of the enzyme by 5'-FSBA. The dissociation constant for the initial reversible enzyme-inhibitor complex was significantly lower and the rate of inactivation was increased when menadione was present during the incubation. However, [14C]5'FSBA labeling was reduced in the presence of menadione. These results are presented and a possible mechanism for the enzyme is discussed.
Chen
S
S
Division of Immunology, Beckman Research Institute, City of Hope, Duarte, California 91010.
Liu
X F
XF
D000241:Adenosine / Q000031:analogs & derivatives* / Q000378:metabolism; D000345:Affinity Labels; D000818:Animals; D004789:Enzyme Activation; D005260:Female; D007700:Kinetics; D008099:Liver / Q000201:enzymology*; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014812:Vitamin K / Q000494:pharmacology*
D000345:Affinity Labels; D014812:Vitamin K; C010959:5'-(4-fluorosulfonylbenzoyl)adenosine; D016660:NAD(P)H Dehydrogenase (Quinone); D000241:Adenosine