Metabolism of R-(+)-and S-(minus)-pentobarbital by hepatic microsomes from male rats.
Hepatic microsomes from male rats hydroxylate R-(+)- and (-)-[2-14-C]pentobarbital to the diasterioisomeric 3'-alcohols: metabolite I (1'RS, 3'SR)- and metabolite II (1'RS, 3'RS)-5-ethyl-5-(3'-hydroxy-1'methylbutyl) barbituric acids. The rate is linear up to 1.5 mg of microsomal protein per ml of incubation mixture and for up to 16 min. The metabolism of R-(+)-pentobarbital led to production of nearly equal quantities of metabolites I and II with a total hydroxylation of 1.08 nmol/min/mg of protein. On the other hand, the S-(-) pentobarbital gave 3- to 5-fold less of metabolite I than II and a total hydroxylation of 1.42 nmol/min/mg of protein. The KM values for formation of metabolite I were 381 muM from R-(+)- and 241 muM from the S-(-)-pentobarbital, while for metabolite II they were 115 muM from R-(+)- and 68 muM from S-(-)-pentobarbital. These data suggest that there are at least two enzymes catalyzing the hydroxylation of pentobarbital, one to give metabolite II and another or others to give metabolite I.
D000818:Animals; D007700:Kinetics; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D006899:Mixed Function Oxygenases / Q000378:metabolism; D008968:Molecular Conformation; D010424:Pentobarbital / Q000378:metabolism*; D051381:Rats; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013997:Time Factors
D006899:Mixed Function Oxygenases; D010424:Pentobarbital