TY  - BOOK
AU  - Ueng,Yune-Fang
AU  - Hsieh,Chih-Hang
AU  - Don,Ming-Jaw
AU  - Chi,Chin-Wen
AU  - Ho,Li-Kang
TI  - Identification of the Main Human Cytochrome P450 Enzymes Involved in Safrole 1'-Hydroxylation
N2  - Safrole is a natural plant constituent, found in sassafras oil and certain other essential oils. The carcinogenicity of safrole is mediated through 1'-hydroxysafrole formation, followed by sulfonation to an unstable sulfate that reacts to form DNA adducts. To identify the main cytochrome P450 (P450)involved in human hepatic safrole 1'-hydroxylation (SOH), we determined the SOH activities of human liver microsomes andEscherichia colimembranes expressing bicistronic human P450s. Human liver (n)18)microsomal SOH activities were in the range of 3.5-16.9 nmol/min/mg protein with a mean value of 8.7(0.7 nmol/min/mg protein. In human liver (n)3)microsomes, the meanKmandVmaxvalues of SOH were 5.7(1.2 mM and 0.14(0.03µmol/min/nmol P450, respectively. The mean intrinsic clearance (Vmax/Km)was 25.3(2.3µL/min/nmol P450. SOH was sensitive to the inhibition by a CYP2C9 inhibitor, sulfaphenazole, and CYP2E1 inhibitors, 4-methylpyrazole and diethyldithiocarbamate. The liver microsomal SOH activity showed significant correlations with tolbutamide hydroxylation (r )0.569)and chlorzoxazone hydroxylation (r )0.770)activities, which were the model reactions catalyzed by CYP2C9 and CYP2E1, respectively. Human CYP2C9 and CYP2E1 showed SOH activities at least 2-fold higher than the other P450s. CYP2E1 showed an intrinsic clearance 3-fold greater than CYP2C9. These results demonstrated that CYP2C9 and CYP2E1 were the main P450s involved in human hepatic SOH
UR  - https://drive.google.com/file/d/1haFdDQ2z7NqBRWSueJ30BMd-NR-Mbf_b/view?usp=drivesdk
ER  -