The reduction of uridine 5'-diphosphate and uridine 5'-triphosphate in some transplantable rat hepatomas.
The reduction of uridine 5'-diphosphate (UDP) and uridine 5'-triphosphate (UTP) has been studied in normal adult rat liver, the Dunning hepatoma, and Morris 5123D and 7793 hepatomas. A new paper chromatographic method that separates and quantitates all the major products of the reduction and hydrolysis or other reactions of the substrate has been devised. All of the above tissues were able to reduce UDP and UTP at relatively slow rates ranging from 0.25 nmole of deoxycompound formed (deoxyuridine 5'-triphosphate) per mg protein per hr for liver to 3.5 nmoles deoxyuridine 5'-triphosphate for the Morris 7793 hepatoma when UTP was the substrate. In general, UTP was a better substrate than UDP. The method may also be used to measure cytidine 5'-diphosphate (CDP) reduction, and under the same conditions, the reduction of CDP proceeded at about 6 times the rate of UTP reduction in the Dunning hepatoma. Like CDP reduction, the reduction of UTP was strongly modulated by ATP. Reduction of UTP was insignificant with no ATP or 1.5 micronmoles ATP added to the reaction mixture and was maximal with 0.25 micronmole. The reduction of UTP was inhibited by deoxyuridine 5'-monophosphate, deoxythymidine 5'-triphosphate, deoxycytidine 5'-triphosphate, and deoxyribose 1'-phosphate. The effects of deoxyadenosine 5'-triphosphate varied, depending on its concentration in the reaction medium and whether UDP or UTP was a substrate. However, hydroxyurea did not inhibit reduction of UDP or UTP at concentrations that strongly inhibited CPD reduction. All of the tissues were able to hydrolyze [alpha-32P]deoxyuridine 5'-triphosphate readily to the diphosphate and monophosphate. It is suggested that the enzyme that reduces UTP or UDP may be different in these tissues from the enzyme that reduces CDP.
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D003853:Deoxyribonucleosides / Q000494:pharmacology; D003854:Deoxyribonucleotides / Q000494:pharmacology; D006868:Hydrolysis; D006918:Hydroxyurea / Q000494:pharmacology; D008099:Liver / Q000378:metabolism; D008113:Liver Neoplasms / Q000378:metabolism*; D008297:Male; D009374:Neoplasms, Experimental / Q000378:metabolism; D010084:Oxidation-Reduction; D051381:Rats; D012264:Ribonucleotide Reductases / Q000037:antagonists & inhibitors / Q000378:metabolism; D014498:Uracil / Q000378:metabolism; D014500:Uracil Nucleotides / Q000378:metabolism*; D014529:Uridine / Q000378:metabolism; D014532:Uridine Diphosphate Glucose / Q000378:metabolism; D014542:Uridine Monophosphate / Q000378:metabolism*
D003853:Deoxyribonucleosides; D003854:Deoxyribonucleotides; D014500:Uracil Nucleotides; D014498:Uracil; D014542:Uridine Monophosphate; D012264:Ribonucleotide Reductases; D014532:Uridine Diphosphate Glucose; D014529:Uridine; D006918:Hydroxyurea