TY - JOUR
T1 - Increased content of cytochrome P-450 and 4-methylpyrazole binding spectrum after 4-methylpyrazole treatment
AU - Feierman, Dennis E.
AU - Cederbaum, Arthur I.
PY - 1985/2/15
Y1 - 1985/2/15
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0021921737&partnerID=8YFLogxK
U2 - 10.1016/0006-291X(85)90295-5
DO - 10.1016/0006-291X(85)90295-5
M3 - Article
C2 - 3977903
AN - SCOPUS:0021921737
SN - 0006-291X
VL - 126
SP - 1076
EP - 1081
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 3
ER -