Glutamine-dependent carbamyl phosphate synthetase during fetal and neonatal life in the rat

George E. Shambaugh*, Suzanne C. Mrozak, Boyd E. Metzger, Norbert Freinkel

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

The pyrimidine-synthesizing enzyme, carbamyl phosphate synthetase II (CP synthetase II) was examined in the rat during normal fetal development and in the fed and calorically deprived neonate. CP synthetase II in the placenta, liver, gut, carcass, and brain showed the following common properties; ability to utilize ammonia as well as l-glutamine as a substrate; negligible enhancement of activity by N-acetyl l-glutamate; inhibition of activity by the glutamine analog, 6-diazo-5-oxo-l-norleucine; and by the phosphorylated pyrimidine uridine 5′-triphosphate. Apparent Km values for l-glutamine of CP synthetase II in placenta and extrahepatic fetal structures were found to vary from 1.1 to 2.3 × 10-5M. In the brain and placenta, tissue concentrations of l-glutamine obtained at serial time points during gestation were at least 200-fold higher. Relative activities for the enzymes catalyzing the subsequent two steps in pyrimidine biosynthesis, aspartate transcarbamylase and dihydroorotase, were substantially greater than CP synthetase II at all times measured and therefore were consistent with the possibility that CP synthetase II may be one of the rate-limiting steps in the de novo biosynthesis of pyrimidines in the placenta and extrahepatic fetal tissues. Serial observations were obtained in placenta, brain, and neonatal muscle to see whether correlations could be demonstrated between concentrations of CP synthetase II per milligram of tissue DNA and daily increments in total tissue DNA. In all these structures, higher concentrations of enzyme were observed during periods of more rapid DNA accumulation. Certain exceptions were also demonstrable. Thus, manifest CP synthetase II activity persisted in the placenta beyond day 16 of gestation (when placental DNA no longer increases); and neonatal muscle exhibited CP synthetase II activity when all net increments in DNA were abolished by caloric deprivation. The latter observations have suggested that the enzyme may be operative (and of possible regulatory significance) even in the absence of cellular proliferation.

Original languageEnglish (US)
Pages (from-to)171-185
Number of pages15
JournalDevelopmental Biology
Volume37
Issue number1
DOIs
StatePublished - Mar 1974

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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