Biogenesis of the mitochondrial enzyme, carbamyl phosphate synthetase. Appearance during fetal development of rat liver an rapid repression in freshly dispersed hepatocytes.
Synthesis of carbamyl phosphate synthetase was undetectable in fetal rat liver at 16 days gestation but by 4-5 days after birth (11-12 days later), this single protein accounted for approx. 5% of total liver protein and roughly 1% of total liver protein synthesis. Likewise, translatable mRNA coding for the enzyme was absent from 16-day fetal livers but then rapidly accumulated reaching maximum levels just after birth. The in vitro primary translation product of carbamyl phosphate synthetase mRNA corresponded to a higher molecular weight biosynthetic precursor of the enzyme; peptide maps obtained from the precursor synthesized both in vivo and in vitro and from the mature enzyme made in vivo were the same. When livers of neonatal rats were perfused with collagenase and further treated to yield a preparation of freshly dispersed hepatocytes highly active in general protein synthesis, a procedure which took about 45 min to complete, biosynthesis of carbamyl phosphate synthetase was found to be completely absent in these cells. The mRNA coding for the enzyme, however, could be extracted from the dispersed hepatocytes and was actively translatable in vitro, at levels approximately 75% of those for mRNA obtained from intact liver. Repression of biogenesis of carbamyl phosphate synthetase in dispersed hepatocytes, therefore, must involve a mechanism which shifts the mRNA coding for the enzyme out of active polysomal complexes and renders it further untranslatable in vivo but not in vitro.
D000818:Animals; D002222:Carbamoyl-Phosphate Synthase (Ammonia) / Q000096:biosynthesis*; D004790:Enzyme Induction; D005260:Female; D008025:Ligases / Q000096:biosynthesis*; D008099:Liver / Q000196:embryology*; D008930:Mitochondria, Liver / Q000201:enzymology*; D011247:Pregnancy; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats
D012333:RNA, Messenger; D008025:Ligases; D002222:Carbamoyl-Phosphate Synthase (Ammonia)