PT  - JOURNAL ARTICLE
AU  - JOHN B. SCHENKMAN
TI  - The Effects of Temperature and Substrates on Component Reactions of the Hepatic Microsomal Mixed-Function Oxidase
DP  - 1972 Mar 01
TA  - Molecular Pharmacology
PG  - 178--188
VI  - 8
IP  - 2
4099  - http://molpharm.aspetjournals.org/content/8/2/178.short
4100  - http://molpharm.aspetjournals.org/content/8/2/178.full
SO  - Mol Pharmacol1972 Mar 01; 8
AB  - The effects of temperature and substrates on components of the hepatic microsomal mixed-function oxidase have been investigated. Aminopyrine caused a 50-100% increase in cytochrome c reductase activity without affecting the apparent activation energy; other substrates of the mixed-function oxidase were without effect. Solubilization of the reductase by deoxycholate did not alter the apparent activation energy or remove the positive modifier action of aminopyrine. Substrates causing the type I spectral change caused a positive modifier effect on NADPH-cytochrome P-450 reductase activity without altering the apparent activation energy (12.7 ± 0.3 kcal/mole). Aniline, which causes a type II spectral change, exerted an apparent negative modifier effect, but also did not alter the apparent activation energy. Benzopyrene, which only causes a type I spectral change in microsomes of polycyclic hydrocarbon-treated animals, exerted a positive modifier action on P-450 reductase only with these microsomes. The rate of microsomal oxidation of aminopyrine (7 nmoles/min/mg at 37°)was the same as the rate of reduction of cytochrome P-450 in the presence of aminopyrine. The rates of oxidation of ethylmorphine (a type I substrate) and aniline were about 50% and 10% of that of aminopyrine, respectively. The activation energies for the three mixed-function oxidations were 12.8 ± 0.5 kcal/mole (aminopyrine), 16.9 ± 0.8 kcal/mole (ethylmorphine), and 20.9 ± 0.8 kcal/mole (aniline). These observations suggest that different steps are rate-limiting in the oxidations of aminopyrine, aniline, and ethylmorphine.