Processing of the precursor for the mitochondrial enzyme, carbamyl phosphate synthetase. Inhibition by rho-aminobenzamidine leads to very rapid degradation (clearing) of the precursor.
Pulse-chase experiments using liver explants incubated in modified Eagle's medium showed that newly synthesized precursor for carbamyl phosphate synthetase (pCPS) passes very rapidly through the cytosolic compartment en route to mitochondria (t 1/2 is approximately 2 min). Since even a small pool of precursor could not be detected in association with mitochondria, processing of pCPS must occur either coincident with or immediately following its transmembrane uptake by the organelle. Treatment of explants with the protease inhibitor, p-aminobenzamidine, however, inhibited normal processing of the precursor. But, rather than accumulate in the cell, newly synthesized pCPS was nonspecifically degraded with kinetics (t 1/2 of 2-3 min) which are consistent with the idea that the precursor was almost instantly degraded upon reaching the blocked processing enzyme in a mitochondrion. The protease inhibitor had little or no effect on synthesis of pCPS. This was determined by isolating polysomes aminobenzamidine; the two polysome preparations were about equally active in synthesizing pCPS in vitro in the presence of an inhibitor of polypeptide chain initiation, aurin tricarboxylic acid.
D000578:Amidines / Q000494:pharmacology*; D000818:Animals; D001550:Benzamidines / Q000494:pharmacology*; D002222:Carbamoyl-Phosphate Synthase (Ammonia) / Q000096:biosynthesis*; D003600:Cytosol / Q000201:enzymology; D004792:Enzyme Precursors / Q000378:metabolism*; D005260:Female; D007700:Kinetics; D008025:Ligases / Q000096:biosynthesis*; D008099:Liver / Q000201:enzymology*; D008297:Male; D008930:Mitochondria, Liver / Q000201:enzymology*; D009924:Organ Culture Techniques; D011132:Polyribosomes / Q000378:metabolism; D014176:Protein Biosynthesis / Q000187:drug effects; D011817:Rabbits; D051381:Rats; D012156:Reticulocytes / Q000378:metabolism
D000578:Amidines; D001550:Benzamidines; D004792:Enzyme Precursors; C006500:4-aminobenzamidine; D008025:Ligases; D002222:Carbamoyl-Phosphate Synthase (Ammonia)