Sex differences in stereospecificity of oracin reductases in rat in vitro and in vivo.
In vitro and in vivo experiments to investigate possible stereospecific aspects of oracin reduction in relation to rat gender have been conducted. Incubation of oracin with rat microsomes, cytosol, and hepatocytes in the presence of various coenzymes and under aerobic or anaerobic conditions provided evidence for sex differences in the formation of 11-dihydrooracin (DHO) enantiomers. The greatest sex differences were seen in hepatocytes where females showed higher stereospecificity of the reductases than males. While female biotransformation enzymes preferentially generated approximately 82% of (+)-DHO, male enzymes gave only rise to 63% of (+)-DHO. Males displayed higher stereospecificity than females in the microsomal fraction. However, in the cytosolic fraction females exhibited higher stereospecificity than males. Similarly, in in vivo studies, the ratio of (+)- and (-)-DHO in faeces and urine gave no indication of the significant differences between the male and female rat. Enzyme stereospecificity has been defined as preferential formation of the (+)- or (-)-stereoisomer of 11-DHO by the respective enzyme. HPLC quantitative determinations of both enantiomers were performed using a Chiralcel OD-R column as the chiral stationary phase with excellent resolution and stability.
Wsól
V
V
Department of Biochemical Sciences, Faculty of Pharmacy, Charles University, Hradec Králové, Czech Republic. wsol@faf.cuni.cz
Skálová
L
L
Szotáková
B
B
Trejtnar
F
F
Kvasnicková
E
E
D000429:Alcohol Oxidoreductases / Q000378:metabolism*; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism* / Q000652:urine; D001711:Biotransformation; D003600:Cytosol / Q000378:metabolism; D004983:Ethanolamines / Q000737:chemistry / Q000378:metabolism* / Q000652:urine; D005243:Feces / Q000737:chemistry; D005260:Female; D066298:In Vitro Techniques; D007546:Isoquinolines / Q000737:chemistry / Q000378:metabolism* / Q000652:urine; D008099:Liver / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D051381:Rats; D012727:Sex Characteristics; D013237:Stereoisomerism; D013379:Substrate Specificity
D000970:Antineoplastic Agents; D004983:Ethanolamines; D007546:Isoquinolines; C103439:oracine; D000429:Alcohol Oxidoreductases; C119935:oracin reductase