Protein degradation in primary monolayer cultures of adult rat hepatocytes. Further evidence for the regulation of protein degradation by amino acids.
Intracellular protein degradation was measured in primary monolayer cultures of adult rat hepatocytes by the loss of radioactivity from proteins pulse-labeled in culture with L-[U-14C]valine. The fractional rate of protein degradation of total protein measured over 18 h was similar to the rate in vivo. The fraction rate of protein breakdown was altered significantly by varying the composition of the chase medium from a balanced salts medium (high rate of protein degradation) to a more complete medium (lower rate of protein degradation). Whereas the vitamin component of the complete medium had some effect, the major portion of the inhibition of protein degradation was due to the essential amino acids in the medium. This inhibition was found to depend on the presence of methonine, phenylalanine, and tryptophan, the latter two of which appear to be primarily responsible. The observed rate of protein breakdown was a function of the level of amino acids in the medium when they were varied in the physiological range for rat plasma. Our results suggest that the regulation of protein degradation by essential amino acids may be physiologically important in maintaining intracellular amino acid pools when the exogenous supply of amino acids is diminished.
D000596:Amino Acids / Q000494:pharmacology*; D000641:Ammonia / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D003470:Culture Media; D005973:Glutamine / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D011506:Proteins / Q000378:metabolism*; D051381:Rats
D000596:Amino Acids; D003470:Culture Media; D007328:Insulin; D011506:Proteins; D005973:Glutamine; D000641:Ammonia