Increased content of cytochrome P-450 and 4-methylpyrazole binding spectrum after 4-methylpyrazole treatment

Dennis E. Feierman, Arthur I. Cederbaum

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

4-Methylpyrazole is a potent inhibitor of alcohol dehydrogenase and of ethanol metabolism. In vitro, 4-methylpyrazole was shown to inhibit microsomal oxidation of drugs and alcohols. Treatment of rats with 4-methylpyrazole at doses ranging from 0 to 300 mg per kg body wt per day for three days resulted in a dose-dependent increase in the content of liver microsomal cytochrome P-450. There was no change in the activity of NADPH-cytochrome P-450 reductase. 4-Methylpyrazole interacted with control microsomes to produce a type II binding spectrum, with a peak at 429 nm, and a trough at 392 nm. The magnitude of this spectral change was increased after 4-methylpyrazole treatment. Kinetic experiments indicated that the 4-methylpyrazole treatment lowered the dissociation constant (Ks) for 4-methylpyrazole. The maximal binding (Vs) was increased when expressed per mg microsomal protein, but not per nmol cytochrome P-450. Therefore, 4-methylpyrazole treatment can affect the microsomal mixed-function oxidase system in several ways, including binding to P-450 as well as inducing P-450.

Original languageEnglish
Pages (from-to)1076-1081
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume126
Issue number3
DOIs
StatePublished - 15 Feb 1985
Externally publishedYes

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