REGIOSELECTIVE HYDROXYLATION AND EPOXIDATION OF LAURIC ACID AND UNSATURATED ANALOGS BY CYTOCHROME-P450 IN JERUSALEM-ARTICHOKE MICROSOMES

Microsomes from aminopyrine induced Jerusalem artichoke tubers catalyz e hydroxylations of lauric acid at C8, C9 and C10 carbon position with a molar metabolite ratio of 1/5.6/2 respectively. We had previously s hown that cytochrome P450 was responsible for the hydroxylation of lau ric (dodecanoic) acid and die epoxidation and allylic hydroxylation of Z and E 9-dodecenoic acids. The incubation of microsomes from aminopy rine induced Jerusalem artichoke tubers with a series of {1-C-14]radio labelled 7-, 8-, 9-, and 10-dodecenoic acids (n-DDNA) produced oxygena ted compounds which have been characterized as epoxy and hydroxy deriv atives by reverse phase-high pressure chromatography and gas chromatog raphy/mass spectrometry analysis. The epoxidation/hydroxylation ratio was directly related to the position, but not to the geometry, of the double bond in the aliphatic chain. Z and E isomers of substrates were oxidized with similar efficiencies. Analysis of metabolites demonstra tes that oxidative attack of this series of unsaturated analogues occu rs with a regioselectivity similar to that of laurate hydroxylation. B ased on specific inhibition of enzyme activities, it was demonstrated that cytochrome P450 monooxygenases carry out hydroxylation at saturat ed carbon positions as well as epoxidation of double bonds.