Cytochrome P 450 isoenzymes, epoxide hydrolase and glutathione transferases in rat and human hepatic and extrahepatic tissues.
The organ distribution of microsomal cytochrome P 450 isoenzymes (P 450), microsomal epoxide hydrolase (EH) and cytosolic glutathione-S-transferases was investigated by immunoblotting and enzyme measurements in rats and humans. In rats, P 450 IA1 was detected only in the duodenum, and P 450 IA2 and IIC11 were detected only in the liver. The highest concentrations of P 450 IIB1/B2 were found in the lung and in the duodenum; pentoxyresorufin-O-dealkylase activity was closely correlated with the amounts of P 450 IIB1/B2 in the different organs. P 450 IIE1 was present in liver, kidney and lung, whereas EH was found in liver, intestine and kidney. In humans, P 450 IIIA4 was detected in all tissues investigated; the highest concentrations were found in liver and intestine. The P 450 IIIA4 level was closely correlated with that of erythromycin demethylase and pentoxyresorufin-O-dealkylase activities. P 450 IIC8-10, IIE1 and IID6 were expressed in liver and intestine, P 450 9 in liver and kidney and P 450 IA2 in liver. EH was identified only in liver, intestine and kidney. In both species, concentrations and total amounts of P 450 isoenzymes and EH were much lower in all extrahepatic tissues than in the liver. Conversely, glutathione-S-transferase-pi was abundant in human intestine and colon compared to liver. Glutathione-S-transferase-mu polymorphism was confirmed in all tissues investigated. This extensive study showed that the pattern of (iso) enzymes was different in all tissues studied; consequently, xenobiotic metabolism would appear to be very different in each type of tissue.
de Waziers
I
I
INSERM U 75, CHU Necker, 75730 Paris, France.
Cugnenc
P H
PH
Yang
C S
CS
Leroux
J P
JP
Beaune
P H
PH
D000818:Animals; D019363:Cytochrome P-450 CYP1A1; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis*; D004851:Epoxide Hydrolases / Q000032:analysis*; D005982:Glutathione Transferase / Q000032:analysis*; D006801:Humans; D007527:Isoenzymes / Q000032:analysis*; D008099:Liver / Q000201:enzymology*; D008297:Male; D010088:Oxidoreductases / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains
D007527:Isoenzymes; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; D019363:Cytochrome P-450 CYP1A1; D005982:Glutathione Transferase; D004851:Epoxide Hydrolases