Vol. 27, Issue 7, 835-841, July 1999

Metabolism of Diallyl Disulfide by Human Liver Microsomal Cytochromes P-450 and Flavin-Containing Monooxygenases

Caroline Teyssier, Lucien Guenot, Marc Suschetet, and Marie-Hélène Siess

Unité de Toxicologie Nutritionnelle, Institut National de la Recherche Agronomique, 21034 Dijon Cedex, France

The metabolism of diallyl disulfide (DADS), a garlic sulfur compound, was investigated in human liver microsomes. Diallyl thiosulfinate (allicin) was the only metabolite observed and its formation followed Michaelis-Menten kinetics with a K_m = 0.61 ± 0.2 mM and a V_max = 18.5 ± 4.2 nmol/min/mg protein, respectively (mean ± S.E.M., n = 4). Both flavin-containing monooxygenase and the cytochrome P-450 monooxygenases (CYP) were involved in DADS oxidation, but the contribution of CYP was predominant. The cytochrome P-450 isoforms involved in this metabolism were investigated using selective chemical inhibitors, microsomes from cells expressing recombinant CYP isoenzymes, and studying the correlation of the rate of DADS oxidation with specific monooxygenase activities of human liver microsomes. Diethyldithiocarbamate and tranylcypromine inhibited allicin formation, whereas other specific inhibitors had low or no effect. Most of the different human microsomes from cells expressing CYP were able to catalyze this reaction, but CYP2E1 showed the highest affinity with a substantial activity. Furthermore, allicin formation by human liver microsomes was correlated with p-nitrophenol hydroxylase activity, a marker of CYP2E1, and tolbutamide hydroxylase activity, a marker of CYP2C9. Among these approaches only CYP2E1 was identified in each case, which suggested that DADS is preferentially metabolized to allicin by CYP2E1 in human liver. However the minor participation of other CYP forms and flavin-containing monooxygenases is likely.