Metabolism of (+)- and (-)-menthols by CYP2A6 in human liver microsomes

J Oleo Sci. 2011;60(3):127-32. doi: 10.5650/jos.60.127.

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.

MeSH terms

  • Aryl Hydrocarbon Hydroxylases / physiology*
  • Catalysis
  • Cells, Cultured
  • Cytochrome P-450 CYP2A6
  • Humans
  • In Vitro Techniques
  • Menthol / chemistry
  • Menthol / metabolism*
  • Microsomes, Liver / enzymology*
  • Microsomes, Liver / metabolism
  • Oxidation-Reduction
  • Stereoisomerism

Substances

  • Menthol
  • Aryl Hydrocarbon Hydroxylases
  • CYP2A6 protein, human
  • Cytochrome P-450 CYP2A6