Inhibitory effects of uridine diphosphate on UDP-glucuronosyltransferase.
Inhibitory effects of uridine diphosphate on the enzymatic activity of UDP-glucuronosyltransferase (UGT) were investigated. Pyrimidine nucleotides such as UDP, UTP and cytidine diphosphate reduced the activity of rat purified UGT (phenol UGT) to about 10%, 48% and 46% of the control, respectively, at the same concentration as a donor substrate, UDP-glucuronic acid. Purine nucleotides, uridine monophosphate, glucuronic acid and some UDP-sugars were only slightly inhibitory toward the transferase. Similar effects were observed in the expressed UGT (UGT1A6; corresponding to phenol UGT) in yeast cells and rat liver microsomal membrane-binding UGT, indicating that uracil and diphosphate residues are essential for the UDP inhibition. Interestingly, 2'-deoxy UDP was found to be a less effective inhibitor (about 50% inhibition) than UDP on the purified, the expressed (UGT1A6 and UGT2B1) and microsomal membrane-binding UGTs. These results indicate that not only uracil and diphosphate residues but also 2'-hydroxyl residue of UDP ribose participates in the interactions between UDP and UDP-glucuronosyltransferase.
Yokota
H
H
Department of Veterinary Biochemistry, School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, Japan.
Ando
F
F
Iwano
H
H
Yuasa
A
A
D000818:Animals; D003001:Cloning, Molecular; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D014453:Glucuronosyltransferase / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000378:metabolism; D051381:Rats; D014530:Uridine Diphosphate / Q000494:pharmacology*; D015003:Yeasts / Q000378:metabolism
D004791:Enzyme Inhibitors; D014530:Uridine Diphosphate; D014453:Glucuronosyltransferase