Comparison of levels of several human microsomal cytochrome P-450 enzymes and epoxide hydrolase in normal and disease states using immunochemical analysis of surgical liver samples.
A group of 100 human liver samples obtained from three different network sources was divided into groups of normal, cirrhotic, metastatic cancer and other disease groups. These samples were analyzed for amounts of cytochrome P-450 IA2, IIC, IIE1 and IIIA and epoxide hydrolase per unit of microsomal protein using sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunochemical staining. For each enzyme the amount of protein detected varied by two orders of magnitude, even within the set of normal liver samples. With respect to the liver samples judged to be normal, the cirrhotic samples showed decreased levels of P-450 IA2 and IIE1 and epoxide hydrolase (P less than .05). The level of P-450 IIIA proteins also appeared lower but the high variance did not allow such a statistically valid conclusion. The liver samples obtained from metastatic cancer patients did not show decreased levels of any of the proteins examined, and levels of P-450 IIC proteins were enhanced in this group compared to the controls. In the samples obtained from patients with other liver diseases, the only major change was a decrease in the level of P-450 IA2. These findings are of use in explaining some of the known effects of hepatic disease on the in vitro and in vivo metabolism of certain drugs.
Guengerich
F P
FP
Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee.
Turvy
C G
CG
D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D004851:Epoxide Hydrolases / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D008103:Liver Cirrhosis / Q000201:enzymology*; D008113:Liver Neoplasms / Q000201:enzymology*; D008862:Microsomes, Liver / Q000201:enzymology*
D003577:Cytochrome P-450 Enzyme System; D004851:Epoxide Hydrolases