Characterization of porcine cytochrome P450 enzymes and their involvement in 3-methylindole metabolism

Wiercinska, Paulina
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University of Guelph

The accumulation of 3-methylindole (3-MI/skatole) in boars is a major contributor to boar taint which ultimately reduces meat quality and jeopardizes animal welfare. The pig is also a potential human model in pharmaceutical studies. In this study, the metabolic characteristics of six porcine CYP450s were investigated; CYP1A1, 2A19, 2C33v4, 2C49, 2E1 and 3A. Chlorzoxazone proved to be a substrate for CYP2E1, CYP2C33v4, CYP1A1, and CYP2A19. CYP2A19 was shown to be specific for coumarin with the ability to metabolize testosterone. The metabolite 16[beta]-OH-testosterone is specifically produced by CYP3A. Tolbutamide was only metabolized by the CYP2C subfamily but was not a probe substrate for CYP2C33v4 or CYP2C49. CYP2C33v4 and CYP2C49 are able to metabolize ETC to 7-OH-TC but also produce an unknown metabolite. All tested isoforms metabolized 3-MI to I3C, 3MOI and 5-0H-3-MI, but only CYP2A19 produced 6-OH-3-MI. Therefore, we have shown that porcine CYP450s are capable of metabolizing human substrates and that CYP2A19 may be an important enzyme in the clearance of 3-MI as it is was shown to produce 6-OH-3-MI

3-methylindole, boars, boar taint, metabolic characteristics, cytochrome P450 enzymes, CYP450