Elucidation of catalytic specificities of human cytochrome P450 and glutathione S-transferase enzymes and relevance to molecular epidemiology.
A number of different approaches have been used to determine the catalytic selectivity of individual human enzymes toward procarcinogens. Studies with cytochrome P450 (P450) enzymes and glutathione S-transferases are summarized here, and recent work with pyrrolizidine alkaloids, aflatoxins, 4,4'-methylenebis(2-chloroaniline), and ethyl carbamate is discussed. In some cases a single enzyme can catalyze both activation and detoxication reactions of a chemical. The purification and characterization of human lung P4501A1 and the development of a noninvasive assay for human P4502E1 are also described.
Guengerich
F P
FP
Department of Biochemistry and Center in Molecular Toxicology, Vanderbilt University School of Medicine, Nashville, TN 37232.
Shimada
T
T
Raney
K D
KD
Yun
C H
CH
Meyer
D J
DJ
Ketterer
B
B
Harris
T M
TM
Groopman
J D
JD
Kadlubar
F F
FF
D016604:Aflatoxin B1 / Q000378:metabolism; D001681:Biological Assay; D002273:Carcinogens / Q000378:metabolism*; D002384:Catalysis; D019392:Cytochrome P-450 CYP2E1; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D005982:Glutathione Transferase / Q000378:metabolism*; D006801:Humans; D008753:Methylenebis(chloroaniline) / Q000378:metabolism; D010084:Oxidation-Reduction; D010089:Oxidoreductases, N-Demethylating / Q000378:metabolism; D011763:Pyrrolizidine Alkaloids / Q000378:metabolism; D014520:Urethane / Q000378:metabolism
D002273:Carcinogens; D011763:Pyrrolizidine Alkaloids; D014520:Urethane; D008753:Methylenebis(chloroaniline); D003577:Cytochrome P-450 Enzyme System; D016604:Aflatoxin B1; D019392:Cytochrome P-450 CYP2E1; D010089:Oxidoreductases, N-Demethylating; D005982:Glutathione Transferase