title: Metabolism of (+)- and (-)-menthols by CYP2A6 in human liver microsomes.
abstract: The in vitro metabolism of (+)-(1S,3S,4R) and (-)-(1R,3R,4S)-menthol enantiomers was examined by incubation with human liver microsomes, and the oxidative metabolites thus formed were analyzed using gas chromatography-mass spectrometry (GC-MS). The (+)- and (-)-menthols were found to be oxidized to the respective (+)-(1S,3S,4S)- and (-)-(1R,3R,4R)-trans-p-menthane-3,8-diol derivatives by human liver microsomal P450 enzymes. Cytochrome P450 (CYP) 2A6 was determined to be the major enzyme involved in the hydroxylation of (+)- and (-)-menthols by human liver microsomes on the basis of the following lines of evidence. First, of 11 recombinant human P450 enzymes tested, CYP2A6 catalyzed the oxidation of (+)- and (-)-menthols. Second, oxidation of (+)- and (-)-menthols was inhibited by (+)-menthofuran and anti-CYP2A6 antibody. Finally, (+)- and (-)-menthol activities were found to correlate with contents of CYP2A6 in liver microsomes of 9 human samples.
authors.affiliation: Department of Applied Chemistry, Faculty of Science and Engineering, Kinki University, Kowakae, Higashiosaka-shi, Osaka, Japan. miyazawa@apch.kindai.ac.jp
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Miyazawa
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Marumoto
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Takahashi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nakahashi
authors.forename: Risa
authors.initials: R
authors.lastname: Haigou
authors.forename: Kyousuke
authors.initials: K
authors.lastname: Nakanishi
mesh_terms: D001189:Aryl Hydrocarbon Hydroxylases / Q000502:physiology*; D002384:Catalysis; D002478:Cells, Cultured; D065637:Cytochrome P-450 CYP2A6; D006801:Humans; D066298:In Vitro Techniques; D008610:Menthol / Q000737:chemistry / Q000378:metabolism*; D008862:Microsomes, Liver / Q000201:enzymology* / Q000378:metabolism; D010084:Oxidation-Reduction; D013237:Stereoisomerism
chemical_list: D008610:Menthol; D001189:Aryl Hydrocarbon Hydroxylases; C585710:CYP2A6 protein, human; D065637:Cytochrome P-450 CYP2A6