Determination of cytochrome P450 enzymes involved in the metabolism of (-)-terpinen-4-ol by human liver microsomes.

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Miyazawa M, Haigou R

Determination of cytochrome P450 enzymes involved in the metabolism of (-)-terpinen-4-ol by human liver microsomes.

Xenobiotica. 2011 Dec;41(12):1056-62. doi: 10.3109/00498254.2011.596230.

PubMed ID

22054099 [ View in PubMed

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Abstract

The in vitro metabolism of (-)-terpinen-4-ol was examined in human liver microsomes and recombinant enzymes. The biotransformation of (-)-terpinen-4-ol was investigated by gas chromatography-mass spectrometry. (-)-Terpinen-4-ol was found to be oxidized to (-)-(1S,2R,4R)-1,2-epoxy-p-menthan-4-ol, major metabolic product by human liver microsomal P450 enzymes. The formation of metabolites of (-)-terpinen-4-ol was determined by relative abundance of mass fragments and retention times on GC. CYP2A6 in human liver microsomes was a major enzyme involved in the oxidation of (-)-terpinen-4-ol by human liver microsomes, based on the following lines of evidence. First, of 11 recombinant human P450 enzymes tested, CYP2A6 had the highest activity for oxidation of (-)-terpinen-4-ol. Second, oxidation of (-)-terpinen-4-ol was inhibited by (+)-menthofuran. Finally, there was a good correlation between CYP2A6 maker activity and (-)-terpinen-4-ol oxidation activities in liver microsomes of 10 human samples. Kinetic analysis showed that the V(max)/K(m) values for (-)-(1S,2R,4R)-1,2-epoxy-p-menthan-4-ol catalysed by liver microsomes of human sample HH-18 was 2.49 muL/min/nmol. Human recombinant CYP2A6 catalysed (-)-(1S,2R,4R)-1,2-epoxy-p-menthan-4-ol with V(max) values of 13.9 nmol/min/nmol P450 and apparent K(m) values of 91 muM.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Terpinen-4-ol	Cytochrome P450 2A6	Protein	Humans	No	Substrate	Details