Detail of "4221-99-2"

Reference

Increased microsomal oxidation of alcohols after pyrazole treatment and its similarities to the induction by ethanol consumption

Increased microsomal oxidation of alcohols after pyrazole treatment and its similarities to the induction by ethanol consumption. Krikun, Graciela; Cederbaum, Arthur I. (Mount Sinai Sch. Med., City Univ. New York, New York, NY 10029, USA). Biochim. Biophys. Acta, 801(1), 131-7 (English) 1984. CODEN: BBACAQ. ISSN: 0006-3002. DOCUMENT TYPE: Journal CA Section: 4 (Toxicology) Microsomes isolated from rats treated daily for 3 days with 200 mg/kg pyrazole (I) [288-13-1], a potent inhibitor of alc. dehydrogenase, catalyzed the oxidn. of EtOH [64-17-5] and 2-BuOH [78-92-2] at rates 2-3-fold higher than saline controls. This increase was blocked by CO, and not assocd. with an increase in the oxidn. of aminopyrine [58-15-1] or the content of cytochrome P 450 [9035-51-2], suggesting the possibility of an induction of an alc.-preferring cytochrome P 450 by I. Microsomes from the I-treated rats displayed a stereochem. preference for the oxidn. of (+)-2-BuOH [4221-99-2] over (-)-2-BuOH [14898-79-4], which was blocked by CO, and also displayed a type-2 binding spectrum with DMSO or 2-BuOH. No such spectrum was found with the saline controls. These properties are similar to those which are obsd. with microsomes from chronic EtOH-fed rats. Thus, I treatment may induce a cytochrome P 450 isozyme with properties similar to the EtOH-inducible cytochrome P 450.

Stereochemical studies on the cytochrome P-450 and hydroxyl radical dependent pathways of 2-butanol oxidation by microsomes from chow-fed, phenobarbital-treated, and ethanol-treated rats

Stereochemical studies on the cytochrome P-450 and hydroxyl radical dependent pathways of 2-butanol oxidation by microsomes from chow-fed, phenobarbital-treated, and ethanol-treated rats. Krikun, Graciela; Cederbaum, Arthur I. (Mt. Sinai Sch. Med., City Univ. New York, New York, NY 10029, USA). Biochemistry, 23(23), 5489-94 (English) 1984. CODEN: BICHAW. ISSN: 0006-2960. DOCUMENT TYPE: Journal CA Section: 4 (Toxicology) Rat liver microsomes oxidized 2-BuOH to 2-butanone by a reaction which was partially sensitive to CO and to competitive OH· scavengers. Desferrioxamine, which completely blocks the prodn. of OH· by microsomes, inhibited the oxidn. of EtOH [64-17-5] by ~60%, whereas the oxidn. of 2-BuOH and 1-BuOH [71-36-3] was decreased by only 30g. Vmax Values for the oxidn. of EtOH, 1-BuOH, and 2-BuOH were 17.7, 6.2, and 23.8 nmol/min-1 (mg of protein)-1, resp., in the absence of desferrioxamine and 5.9, 4.7, and 13.6 nmol/min-1 (mg of protein)-1, resp., in the presence of desferrioxamine. 2-BuOH appears to be a particularly good alc. substrate for the cytochrome P 450 [9035-51-2] dependent pathway of alc. oxidn. Chronic EtOH consumption, which induces the microsomal alc. oxidizing system, resulted in a 3-fold increase in the rate of 2-BuOH oxidn. Most of this increment reflected an increased rate of metab. by the cytochrome P 450 pathway. A type 2 binding spectrum was obsd. for the interaction of 2-BuOH with microsomes from EtOH-fed rats, but not with controls. Hence, 2-BuOH appears to be a very good alc. substrate for the EtOH-inducible cytochrome P 450. The rates of oxidn. of racemic 2-BuOH [15892-23-6], (+)-2-BuOH [4221-99-2] and (-)-2-BuOH [14898-79-4] were the same for (a) model OH·-generating systems, (b) microsomes from chow-fed rats, and (c) microsomes from phenobarbital-treated rats. These results suggest that the OH·-dependent and the cytochrome P 450-dependent pathways of alc. oxidn. by these microsomes do not display stereospecificity. By contrast, microsomes from the chronic EtOH-fed rats catalyzed the oxidn. of the (+) enantiomer at rates twice that of the (-) enantiomer of 2-BuOH. These differences were obsd. only for the cytochrome P 450-dependent pathway. Thus, the stereospecificity displayed by microsomes from chronic alc. fed rats may be due to the induction of a particular cytochrome P 450. Stereochem. studies may be of value in elucidating the mechanism and the identification of the EtOH-inducible cytochrome P 450.