UDP-glucuronosyltransferase activity toward digitoxigenin monodigitoxoside in human liver microsomes.
The properties of UDP-glucuronosyltransferase (UDPGT) toward digitoxigenin-monodigitoxoside (DT1) have been studied in human liver microsomes. The enzyme activity determined in nonactivated microsomes was very low (20 pmol/min/mg protein) compared with previously published values in rats (104 pmol/min/mg protein) or mice (379 pmol/min/mg protein) DT1-UDPGT activity was increased (180 to 220% of control activity) by Lubrol PX, Triton X-100, or (3-[3-cholamidopropyl]dimethylammonio)-1-propane sulfonic acid. The rate of DT1 glucuronidation determined for 29 different human liver microsomes was variable (18 to 87 pmol/min/mg protein). The KM found was approximately 4.5 microM. DT1-UDPGT activity was tentatively correlated with other known UDPGT activities. No significant correlations were found between DT1 and p-nitrophenol or 4-hydroxybiphenyl UDPGT activities. On the other hand, a strong correlation (r = 0.64, p < 0.05) was observed between DT1-UDPGT activity and digoxigenin-monodigitoxoside (DG1, another cardiac glycoside) glucuronidation rate.
Lacarelle
B
B
Laboratoire de Toxicocinétique et Pharmacocinétique, Faculté de Pharmacie, Marseille, France.
Rajaonarison
J F
JF
Catalin
J
J
Durand
A
A
Cano
J P
JP
D000293:Adolescent; D000328:Adult; D001713:Biphenyl Compounds / Q000378:metabolism; D004073:Digitoxigenin / Q000031:analogs & derivatives* / Q000378:metabolism; D005260:Female; D005965:Glucuronates / Q000378:metabolism; D014453:Glucuronosyltransferase / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D008875:Middle Aged; D009596:Nitrophenols / Q000378:metabolism
D001713:Biphenyl Compounds; D005965:Glucuronates; D009596:Nitrophenols; D004073:Digitoxigenin; C035486:digitoxigenin monodigitoxoside; C019046:4-phenylphenol; D014453:Glucuronosyltransferase; C024836:4-nitrophenol