Glutamine-dependent carbamoyl phosphate synthetase: polyamines inhibit the activity and modify the activating effect of 5-phosphoribosyl 1-pyrophosphate.

Mammalian glutamine-dependent carbamoyl phosphate synthetase (EC 2.7.2.9), the first enzyme of $\text{de novo}$ pyrimidine nucleotide biosynthesis, was strongly inhibited by polyamines at concentrations of 10^?4 to 10^?3 M. Spermine was the most effective, followed in order by spermidine and putrescine. The inhibition was partially reversed by increasing the concentration of Mg²⁺ or MgATP^2?, or by adding low concentrations of 5-phosphoribosyl 1-pyrophosphate, an allosteric activator of the enzyme. Polyamines increased the apparent $\text{K}{}_{\mathrm{a}}$ value of the enzyme for phosphoribosyl pyrophosphate. A possible physiological role of polyamines in widening the range of the effective concentrations of phosphoribosyl pyrophosphate as the activator for the enzyme is suggested.