Influence of branched-chain amino acids and branched-chain keto acids on protein synthesis in isolated hepatocytes.
We investigated the effects of the branched-chain amino acids--valine, leucine and isoleucine--or their keto analogs, the branched-chain keto acids--alpha-ketoisovaleric acid, alpha-ketoisocaproic acid and alpha-keto-beta-methylvaleric acid--on protein synthesis and secretion by monolayers of rabbit hepatocytes incubated with [35S] methionine in pulse-chase and steady-state experiments. The branched-chain amino acids (2.0 mM or 1.0 mM), in the presence or absence of insulin (2 X 10(-4) IU per dish) and in both types of experiments, reduced the trichloroacetic acid-precipitable 35S-protein secreted into the medium. The branched-chain keto acids (2.0 mM or 1.0 mM) had a stimulatory effect on secreted trichloroacetic acid-precipitable 35S-protein which was observed only by the pulse-chase technique in the presence of insulin. Immunoaffinity chromatography of medium demonstrated a slight inhibition by branched-chain amino acids and a slight stimulation by branched-chain keto acids on secretion of 35S-albumin and no effect of either treatment on secretion of 35S-fibrinogen. ELISA analysis of total (i.e., 35S-labeled and unlabeled) secreted albumin revealed an inhibitory effect of the branched-chain amino acids in both pulse-chase and steady-state experiments, and a small stimulatory effect, in steady-state experiments, of the branched-chain keto acids; both effects were insulin-dependent. Total secreted fibrinogen, under steady-state conditions, was increased by the branched-chain keto acids in the presence of insulin, while transferrin production was unaffected by any treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
D000597:Amino Acids, Branched-Chain / Q000494:pharmacology*; D000818:Animals; D045782:Hemiterpenes; D066298:In Vitro Techniques; D007532:Isoleucine / Q000494:pharmacology; D007651:Keto Acids / Q000494:pharmacology*; D007930:Leucine / Q000494:pharmacology; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008297:Male; D014176:Protein Biosynthesis; D011817:Rabbits; D014633:Valine / Q000494:pharmacology
D000597:Amino Acids, Branched-Chain; D045782:Hemiterpenes; D007651:Keto Acids; D007532:Isoleucine; C016211:alpha-keto-beta-methylvaleric acid; C001505:alpha-ketoisovalerate; C013082:alpha-ketoisocaproic acid; D007930:Leucine; D014633:Valine