Babol J, Squires E J, Lundström K
Department of Food Science, Swedish University of Agricultural Sciences, Uppsala.
J Anim Sci. 1998 Mar;76(3):822-8. doi: 10.2527/1998.763822x.
High concentrations of skatole in fat are a major cause of boar taint in intact male pigs. Skatole is metabolized in the liver, and this metabolism could affect concentrations of skatole in fat. In this study, we evaluated the involvement of cytochrome P450, in particular cytochrome P4502E1, in skatole metabolism in pig liver. Liver microsomes from F4 European Wild Pig x Swedish Yorkshire intact male pigs were incubated in a buffer containing NADPH, NADH, and skatole. Several skatole metabolites were detected by HPLC, including 6-hydroxyskatole (pro-MII), 3-hydroxy-3-methyloxyindole (MIII), and five others not identified in this study. Inhibitors of P450 were added to microsomal incubations, and their effect on the formation of skatole metabolites and skatole disappearance was evaluated. The general cytochrome P450 inhibitors SKF 525A, at a concentration of .2 mM and metyrapone, at a concentration of .1 mM decreased the formation of pro-MII (P = .001) to 38.2 and 11.6%, respectively, of that of controls. The SKF 525A also reduced the synthesis of MIII and three other metabolites, whereas metyrapone only reduced the disappearance of skatole and synthesis of pro-MII. Inhibitors specific for cytochrome P4502E1 were more effective in reducing the formation of skatole metabolites than SKF 525A and metyrapone. Chlorzoxazone and diallyl sulfide reduced (P = .001) the synthesis of pro-MII to 9.7 and 30.9% of the control rate. The formation of most of the other skatole metabolites and disappearance of skatole were also reduced with these inhibitors. These results indicate that skatole is metabolized in pig liver to pro-MII and other metabolites by cytochrome P4502E1.
脂肪中高浓度的粪臭素是未阉割公猪产生公猪膻味的主要原因。粪臭素在肝脏中代谢，这种代谢可能会影响脂肪中粪臭素的浓度。在本研究中，我们评估了细胞色素P450，特别是细胞色素P4502E1在猪肝粪臭素代谢中的作用。将F4欧洲野猪×瑞典约克郡未阉割公猪的肝微粒体在含有NADPH、NADH和粪臭素的缓冲液中孵育。通过高效液相色谱法检测到几种粪臭素代谢物，包括6-羟基粪臭素（前MII）、3-羟基-3-甲氧基吲哚（MIII），以及本研究中未鉴定出的其他五种代谢物。将P450抑制剂添加到微粒体孵育体系中，并评估它们对粪臭素代谢物形成和粪臭素消失的影响。一般细胞色素P450抑制剂SKF 525A（浓度为0.2 mM）和甲吡酮（浓度为0.1 mM）分别将前MII的形成降低至对照组的38.2%和11.6%（P = 0.001）。SKF 525A还降低了MIII和其他三种代谢物的合成，而甲吡酮仅降低了粪臭素的消失和前MII的合成。细胞色素P4502E1特异性抑制剂在减少粪臭素代谢物形成方面比SKF 525A和甲吡酮更有效。氯唑沙宗和二烯丙基硫醚将前MII的合成降低（P = 0.001）至对照速率的9.7%和30.9%。使用这些抑制剂也降低了大多数其他粪臭素代谢物的形成和粪臭素的消失。这些结果表明，粪臭素在猪肝中通过细胞色素P4502E1代谢为前MII和其他代谢物。
