De novo pyrimidine biosynthesis in isolated rat hepatocytes. Quantitative aspects of the regulation by UTP.
Quantitative aspects of de novo pyrimidine biosynthesis in rat hepatocytes were monitored. A reduction of intracellular UTP contents by different concentrations of D-galactosamine led to a dose-dependent increase of 14CO2 incorporation into the sum of all acid-soluble uracil nucleotides. In controls the rate of de novo synthesis which was calculated from the incorporation rate of 14CO2 into the sum of all acid-soluble uracil nucleotides was 0.014 mumol X h-1 X g-1 compared to 0.056 mumol X h-1 X g-1 wet weight of liver in situations of a maximally stimulated de novo synthesis. Incubation of hepatocytes with uridine led to a dose-dependent reduction of 14CO2 incorporation to less than 25% of the amount incorporated in the controls. Alterations of the CTP content had no influence on the 14CO2 incorporation. In the presence of high D-galactosamine concentrations the increase of the total amount of acid-soluble uracil nucleotides exceeded the rate of the de novo synthesis derived from the incorporation of 14CO2 into the sum of the acid-soluble uracil nucleotide pool. It was also greater than the increase of the total amount of intra- and extracellular orotate after acidic hydrolysis--even in the presence of 6-azauridine, which stimulated de novo pyrimidine biosynthesis by itself.
D000255:Adenosine Triphosphate / Q000032:analysis; D000818:Animals; D002245:Carbon Dioxide / Q000378:metabolism; D003570:Cytidine Triphosphate / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D005260:Female; D005688:Galactosamine / Q000494:pharmacology; D006160:Guanosine Triphosphate / Q000032:analysis; D008099:Liver / Q000378:metabolism*; D008433:Mathematics; D009963:Orotic Acid / Q000378:metabolism; D011743:Pyrimidines / Q000096:biosynthesis*; D051381:Rats; D011919:Rats, Inbred Strains; D014500:Uracil Nucleotides / Q000502:physiology*; D014529:Uridine / Q000378:metabolism; D014542:Uridine Monophosphate / Q000378:metabolism; D014544:Uridine Triphosphate / Q000502:physiology*
D011743:Pyrimidines; D014500:Uracil Nucleotides; D002245:Carbon Dioxide; D009963:Orotic Acid; D003570:Cytidine Triphosphate; D005688:Galactosamine; D006160:Guanosine Triphosphate; D000255:Adenosine Triphosphate; D014542:Uridine Monophosphate; D014544:Uridine Triphosphate; D014529:Uridine