Synthesis and Intracellular Transport of Mitochondrial Carbamyl Phosphate Synthetase I and Ornithine Transcarbamylase
Carbamyl phosphate synthetase I (CPS) and ornithine transcarbamylase (OTC), the first two enzymes of urea synthesis, are localized in the liver mitochondrial matrix of ureotelic animals.1 The two enzymes are coded by nuclear genes, synthesized on cytoplasmic 80 S ribosomes, and subsequently transported across the two mitochondrial membranes to the matrix space. Studies in our2,3 and other laboratories4,5 have shown that both enzymes are synthesized in larger precursor forms (pCPS and pOTC) in cell-free protein-synthesizing systems. These precursors form large aggregates and have conformations different from those of the mature enzymes.6 We further showed that pOTC was transported into isolated rat liver mitochondria in association with the processing of pOTC to the mature form of the enzyme.3,7,8 It has been shown that both pCPS9 and pOTC10 are synthesized on membrane-free polysomes, released into the cytosol and then transported rapidly into mitochondria. The present paper describes detailed kinetic studies of the synthesis, processing and intracellular transport of pCPS and pOTC in isolated rat hepatocytes. The paper also deals with the chemical nature of pOTC and its transport into isolated mitochondria in vi vitro.
KeywordsIntracellular Transport Flufenamic Acid Mature Enzyme Ornithine Transcarbamylase Putative Precursor
carbamyl phosphate synthetase I
precursor of carbamyl phosphate synthetase I
precursor of ornithine transcarbamylase
sodium dodecyl sulfate.
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