Effect of polyamines on the carbamoyl-phosphate synthase activity of CAD protein.
The effects of polyamines were studied on carbamoyl-phosphate synthase II (EC 6.3.5.5.) which is the first and rate limiting enzyme in mammalian pyrimidine synthesis. Polyamines in physiological concentrations (0.1-1 mM) strongly inhibited the carbamoyl-phosphate synthesis. Of the polyamines tested spermine was the most effective followed by spermidine and putrescine. Spermine increased the KM for ATP and the requirement for Mg++ of carbamoyl-phosphate synthase reaction. UTP, an inhibitor, had similar, while phosphoribosyl-pyrophosphate, an activator of the enzyme had an opposite effect. Increasing concentrations of phosphoribosyl-pyrophosphate completely reversed the inhibition caused by spermine, while did not influence the degree of inhibition caused by UTP. A possible physiological role of polyamines in synchronizing the substrate and activator functions of phosphoribosyl-pyrophosphate in pyrimidine synthesis is suggested.
Szondy
Z
Z
Department of Biochemistry, University Medical School of Debrecen, Hungary.
Matyasi
G
G
Elödi
P
P
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000581:Amidohydrolases / Q000378:metabolism*; D000818:Animals; D001221:Aspartate Carbamoyltransferase / Q000378:metabolism*; D002223:Carbamoyl-Phosphate Synthase (Glutamine-Hydrolyzing) / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D004080:Dihydroorotase / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D007700:Kinetics; D008099:Liver / Q000201:enzymology; D008274:Magnesium / Q000494:pharmacology; D009097:Multienzyme Complexes / Q000378:metabolism*; D010754:Phosphoribosyl Pyrophosphate / Q000494:pharmacology; D011073:Polyamines / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D014544:Uridine Triphosphate / Q000494:pharmacology
C033626:CAD trifunctional enzyme; D009097:Multienzyme Complexes; D011073:Polyamines; D010754:Phosphoribosyl Pyrophosphate; D000255:Adenosine Triphosphate; D001221:Aspartate Carbamoyltransferase; D000581:Amidohydrolases; D004080:Dihydroorotase; D002223:Carbamoyl-Phosphate Synthase (Glutamine-Hydrolyzing); D008274:Magnesium; D014544:Uridine Triphosphate