title: In Vitro Regio- and Stereoselective Oxidation of β-Ionone by Human Liver Microsomes.
abstract: The metabolism of the norisoprenoidβ-ionone was investigatedin vitrousing human liver microsomes and 11 different recombinant cytochrome P450 enzymes expressed inTrichoplusia nicells.β-Ionone was found to be oxidized via 4S-hydroxylation by CYP2B6 in human liver microsomes. CYP1A2 also regioselectively catalyzed the hydroxylation ofβ-ionone to yield 4-hydroxylation; this conversion was not stereoselective. Further kinetic analysis revealed that CYP2B6 exhibited the highest activity forβ-ionone 4-hydroxylation. Kinetic analysis showed thatKmandVmaxfor oxidation ofβ-ionone by CYP1A2 and CYP2B6 was 107.9 ± 36.0 µM and 3200.3 ± 323.0 nmol/min/nmol P450 and 5.6 ± 1.2 µM and 572.8 ± 29.8 nmol/min/nmol P450, respectively. The reaction rates observed using human liver microsomes and recombinant CYP2B6 were very high compared with those of other CYP2B6 substrates reported thus far. These results suggest thatβ-ionone, a norisoprenoid present in nature, is one of the effective substrates for CYP2B enzymes in human liver microsomes. To the best of our knowledge, this is the first time that 4-hydroxyβ-ionone has been described as a human metabolite ofβ-ionone.
authors: Joint Research Center, Kinki (Kindai) University, Kowakae, Higashiosaka-shi, Osaka, Japan.
authors: Shinsuke
authors: S
authors: Marumoto
authors: Department of Applied Chemistry, Faculty of Science and Engineering, Kinki (Kindai) University, Kowakae, Higashiosaka-shi, Osaka, Japan.
authors: Ryoyu
authors: R
authors: Shimizu
authors: Pharmaceutical Research and Technology Institute, Kinki (Kindai) University, Higashi-osaka, Osaka, Japan.
authors: Genzoh
authors: G
authors: Tanabe
authors: Department of Materials Science, Wakayama National College of Technology, Gobo, Wakayama Japan.
authors: Yoshiharu
authors: Y
authors: Okuno
authors: Department of Applied Chemistry, Faculty of Science and Engineering, Kinki (Kindai) University, Kowakae, Higashiosaka-shi, Osaka, Japan.
authors: Mitsuo
authors: M
authors: Miyazawa
mesh_terms: D001711:Biotransformation; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D006801:Humans; D008862:Microsomes, Liver / Q000378:metabolism*; D045792:Norisoprenoids / Q000378:metabolism* / Q000494:pharmacology; D010084:Oxidation-Reduction; D011994:Recombinant Proteins / Q000378:metabolism; D013237:Stereoisomerism
chemical_list: D045792:Norisoprenoids; D011994:Recombinant Proteins; D003577:Cytochrome P-450 Enzyme System; C008157:beta-ionone