Porcine CYP2A19, CYP2E1 and CYP1A2 forms are responsible for skatole biotransformation in the reconstituted system.
OBJECTIVE
To study the contribution of individual purified porcine CYP1A2, 2E1 and 2A19 enzymes to the biotransformation of skatole.


METHODS
Individual porcine and human enzymes (CYP1A2, 2E1 or 2A6/19) were used to study their potential involvement in skatole metabolism. Furthermore, the inhibition experiments using specific inhibitors of CYP1A2, 2E1 or 2A6/19, were performed. For determination of skatole biotransformation by individual CYP forms in reconstituted systems, HPLC method with UV detection was used.


RESULTS
The data presented in this paper show that porcine and human CYPs are responsible for the formation of indole-3-carbinol and 3-methyloxindole. Whereas in pig CYP2A19 and CYP1A2 seem to be the most important for metabolism of skatole, in man CYP1A2 and CYP2E1 forms are mainly responsible for the production of the metabolites mentioned above.


CONCLUSIONS
The porcine and human CYP1A2, 2E1, 2A6/19 forms contribute to formation of 3-methyloxindole and indole-3-carbinol.
Matal
Jaroslav
J
Department of Pharmacology, Palacky University, Olomouc, Czech Republic.
Matuskova
Zuzana
Z
Tunkova
Alena
A
Anzenbacherova
Eva
E
Anzenbacher
Pavel
P
D000818:Animals; D019388:Cytochrome P-450 CYP1A2 / Q000378:metabolism*; D065609:Cytochrome P-450 CYP1A2 Inhibitors; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism*; D065691:Cytochrome P-450 CYP2E1 Inhibitors; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D006801:Humans; D007211:Indoles / Q000378:metabolism; D000078183:Oxindoles; D012862:Skatole / Q000378:metabolism*; D013552:Swine
D065609:Cytochrome P-450 CYP1A2 Inhibitors; D065691:Cytochrome P-450 CYP2E1 Inhibitors; D065607:Cytochrome P-450 Enzyme Inhibitors; D007211:Indoles; D000078183:Oxindoles; C402671:cytochrome P-450 CYP1A6 (fish); C035500:3-methyloxindole; D003577:Cytochrome P-450 Enzyme System; D012862:Skatole; C016517:indole-3-carbinol; D019392:Cytochrome P-450 CYP2E1; D019388:Cytochrome P-450 CYP1A2