The stereoselective enzymic reduction of the synthetic 9-ketocannabinoid, nabilone, in vivo, in isolated liver cells and in liver homogenate.
1. The enzymic reduction of the two optical isomers of nabilone, 6aR, 10aR and 6aS, 10aS, has been studied separately in the rat, in isolated hepatocytes, and in the 9000 g supernatant fraction of rat liver homogenate. The SS-nabilone was the more active substrate in all three cases. 2. In all three systems, the only carbinol formed from SS-nabilone was the S-(equatorial)-carbinol. In contrast, the reduction of RR-nabilone gave only S-(axial)-carbinol in the intact rat and in the isolated hepatocyte, but gave in the liver homogenate fraction a mixture of S-(axial)-carbinol and R-(equatorial)-carbinol. 3. The results show that the reduction of nabilone in vivo in the rat proceeds with rigid stereochemical control and that only the S-carbinols are formed. 4. The results also suggest that observations made with the intact liver cell may be more predictive of events in vivo than are those made with broken cell preparations.
D000818:Animals; D013759:Dronabinol / Q000031:analogs & derivatives* / Q000378:metabolism; D066298:In Vitro Techniques; D008099:Liver / Q000166:cytology / Q000201:enzymology / Q000378:metabolism* / Q000648:ultrastructure; D008968:Molecular Conformation; D009243:NAD / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000378:metabolism; D051381:Rats; D013237:Stereoisomerism; D013347:Subcellular Fractions / Q000378:metabolism
D009243:NAD; C011941:nabilone; D009249:NADP; D013759:Dronabinol; D010088:Oxidoreductases