Glutamine utilization in both the arginine-specific and pyrimidine-specific carbamoyl phosphate synthase enzymes of Neurospora crassa

Abstract

As glutamine-dependent carbamoyl phasphate synthetase (CPS) activity in some organisms is composed of a glutaminase and an ammonium-dependent CPS, CPS- mutants in Neurospora crassa were examined for glutamine- and ammonium-dependent CPS activities. No evidence was found that the genetic location of these two functions were separable. This is discussed with reference to the close genetic proximity of the CPSpyr and aspartate carbamoyltransferase (ACT) structural gene (pyr-3) and the arg-2 gene which appears to specify a subunit responsible for glutamine utilisation in CPSarg.

Metabolic analysis of the asparagine and glutamine dynamics in an industrial Chinese hamster ovary fed‐batch process

“…NAG serves as an activator of the initial steps of the urea cycle, which are identical to those in pyrimidine synthesis Glutathione is synthesized from the amino acids cysteine, glycine, and glutamate (c). N-acetyl glutamate (NAG) is synthesized from acetyl-CoA and glutamate from (d) (Anderson, 1981;Holden et al, 1999;Levenberg, 1962;Makoff & Radford, 1976) although NAG is not known to promote the pyrimidine pathway. Increased expression of urea cycle enzymes in the CHO cells is known to result in reduced accumulation of ammonium ions in the culture medium (Chung et al, 2003).…”

Metabolism of Pyrimidines and Purines

“…The arginine-2 gene coding for glutamine utilization in the arginine-specific CPS is extremely close to the pyrimidine-3 gene coding for CPS-ATC. However, the suggested functional relationship through a common glutaminase activity could not be found (MAKOFF and RADFORD 1976b). The CPS-ATC complex was localized histochemically in the nucleus, while the highly unstable arginine-specific CPS (t1 2 = 35 min at 25 DC) ) and ornithine transcarbamylase were localized in the mitochondria (BERNHARDT and DAVIS 1972).…”

Genetics and biochemistry of carbamoyl phosphate biosynthesis and its utilization in the pyrimidine biosynthetic pathway.

“…Although the CPSpyr-ACT complex is oligomeric, CPSpyr ac-tivity appears to comprise only one polypeptide type. This is strongly suggested by the finding that, of the many pyr-3 alleles examined, none with little or no glutamine-dependent CPSpyr activity owed their mutation to a loss of the glutamine binding site (94).…”

“…There are four lines of evidence to show that this close proximity has no functional significance: (i) Studies by Cybis and Davis (32) showed that the arg-2 gene product is subject to powerful repression by arginine. (ii) No pyr-3 CPS-ACT-polar mutant has an arginine requirement (94). (iii) Mutants at arg-2 have normal glutamine-dependent CPSpyr activities (93).…”