Effect of uridine on hepatic galactose-1-phosphate uridyltransferase.
Uridine sugar nucleotides are important intermediates in galactose metabolism and may play a role in the long-term galactose toxicity in human galactose-1-phosphate uridyltransferase deficiency galactosemia. Since administration of uridine, a precursor of uridine nucleotides, has been considered as a therapeutic measure, we have investigated the effects of this compound on the activity of rat hepatic transferase. Uridine has been found to be an inhibitor of the enzyme in in vitro studies and to cause an increase in galactose-1-phosphate in liver perfused with galactose which is consistent with physiologic inhibition of the enzyme. Uridine is a partial linear competitive inhibitor of UDPglucose and an uncompetitive inhibitor of galactose-1-phosphate. These findings suggest caution should be applied in giving the compound to subjects with genetically limited transferase activity because of the possibility of inhibiting the small amount of residual enzyme.
Rogers
S
S
Division of Biomedical Development and Molecular Diseases, Children's Hospital of Philadelphia, Pa.
Bovee
B W
BW
Segal
S
S
D000375:Aging / Q000378:metabolism; D000818:Animals; D005690:Galactose / Q000378:metabolism; D005695:Galactosephosphates / Q000378:metabolism; D005958:Glucosephosphates / Q000378:metabolism; D008099:Liver / Q000201:enzymology* / Q000378:metabolism; D008297:Male; D009713:Nucleotidyltransferases / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D005694:UTP-Hexose-1-Phosphate Uridylyltransferase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014529:Uridine / Q000494:pharmacology*; D014532:Uridine Diphosphate Glucose / Q000494:pharmacology
D005695:Galactosephosphates; D005958:Glucosephosphates; D009713:Nucleotidyltransferases; D005694:UTP-Hexose-1-Phosphate Uridylyltransferase; D014532:Uridine Diphosphate Glucose; D014529:Uridine; D005690:Galactose