Site of action of isoniazid on the electron transport chain and its relationship to nicotinamide adenine dinucleotide regulation in Mycobacterium phlei.
Isoniazid (INH) interacts with nicotinamide adenine dinucleotide (NAD+) in the regulation of reduced NAD (NADH) oxidation in electron transport particles from Mycobacterium phlei. the interaction was shown to be at the level of the NADH dehydrogenase by the use of menadione as an artificial electron acceptor. Binding studies indicated that INH and NAD+ did not compete for a common regulatory site. Unlabeled INH was unable to displace [14C]NAD+ from electron transport particles, and unlabeled NAD+ could not remove [3H]INH from particles. Preincubation of electron transport particles with unlabeled INH did not prevent the subsequent binding of [14C]NAD+, and unlabeled NAD+ did not block the binding of [3H]INH. [14C]NAD+ binding to electron transport particles was specific and reversible. Unlabeled NAD+ could both displace and prevent the binding of labeled nucleotide. Binding of [14C]NAD+ to electron transport particles was proportional to the incubation concentration of label, and NAD+ stimulation of NADH oxidase activity was related to the amount of NAD+ bound to electron transport particles. [3H]INH was irreversibly bound to electron transport particles. INH and NAD+, although operating at the same level of the electron transport chain, did not appear to compete for the same regulatory site.
D001665:Binding Sites; D003579:Cytochrome Reductases / Q000378:metabolism*; D004579:Electron Transport / Q000187:drug effects; D007538:Isoniazid / Q000378:metabolism / Q000494:pharmacology*; D009161:Mycobacterium / Q000187:drug effects*; D009168:Mycobacterium phlei / Q000187:drug effects* / Q000378:metabolism; D009243:NAD / Q000378:metabolism*; D009245:NADH Dehydrogenase / Q000378:metabolism*; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism*; D014812:Vitamin K / Q000378:metabolism
D009243:NAD; D014812:Vitamin K; D009247:NADH, NADPH Oxidoreductases; D003579:Cytochrome Reductases; D009245:NADH Dehydrogenase; D007538:Isoniazid