[Mechanism of the effect of serine and threonine on ammoniagenesis and biosynthesis of orotate in the mouse].

We have evaluated the effects of serine and threonine on orotate metabolism in mice, by injecting i.p. 0.5 to 1.5 mmol/100 g of body weight, during 4 weeks of experimentation. The results indicate that serine as well as threonine cause a significant increase (p less than 0.01) of plasma ammonia and urinary orotate. We have also studied the effects of various inhibitors, adenine (0.3% diet), N-(phosphonoacetyl)-L-aspartate (PALA) (10 mg/100 g, i.p.), acivicin (1 mg/100 g, i.p.) and cycloheximide (1.5 mg/kg, i.p.) on orotate synthesis in mice injected with serine (2.5 mmol/100 g, i.p.) or threonine (1.25 mmol/100 g, i.p.). The results show an increase (p less than 0.05) of urinary orotate following an adenine-rich diet, and a reduction of orotate following PALA (p less than 0.01). The orotic aciduria remained insensitive to acivicin while it was inhibited by cycloheximide. These results suggest that adenine blocks the utilisation of orotate and consequently could affect the biosynthesis of pyrimidines; the induction of orotate by serine and threonine is controlled by the translation of a specific protein synthesis, and necessarily implicates the mitochondrial carbamyl phosphate synthetase-I (CPS-I). The regulating step in this synthesis of orotate could also be the transport of carbamyl-phosphate from the mitochondria to cytosol.