Skip to main content
NCBI home page
Biochemical Journal logoLink to Biochemical Journal
. 1984 Sep 15;222(3):579–586. doi: 10.1042/bj2220579

Specificity of the effects of leucine and its metabolites on protein degradation in skeletal muscle.

W E Mitch, A S Clark
PMCID: PMC1144218  PMID: 6487265

Abstract

The effects of leucine, its metabolites, and the 2-oxo acids of valine and isoleucine on protein synthesis and degradation in incubated limb muscles of immature and adult rats were tested. Leucine stimulated protein synthesis but did not reduce proteolysis when leucine transamination was inhibited. 4-Methyl-2-oxopentanoate at concentrations as low as 0.25 mM inhibited protein degradation but did not change protein synthesis. The 2-oxo acids of valine and isoleucine did not change protein synthesis or degradation even at concentrations as high as 5 mM. 3-Methylvalerate, the irreversibly decarboxylated product of 4-methyl-2-oxopentanoate, decreased protein degradation at concentrations greater than or equal to 1 mM. This was not due to inhibition of 4-methyl-2-oxopentanoate catabolism, because 0.5 mM-3-methylvalerate did not suppress proteolysis, even though it inhibited leucine decarboxylation by 30%; higher concentrations of 3-methylvalerate decreased proteolysis progressively without inhibiting leucine decarboxylation further. During incubation with [1-14C]- and [U-14C]-leucine, it was found that products of leucine catabolism formed subsequent to the decarboxylation of 4-methyl-2-oxopentanoate accumulated intracellularly. This pattern was not seen during incubation with radiolabelled valine. Thus, the effect of leucine on muscle proteolysis requires transamination to 4-methyl-2-oxopentanoate. The inhibition of muscle protein degradation by leucine is most sensitive to, but not specific for, its 2-oxo acid, 4-methyl-2-oxopentanoate.

Full text

PDF
579

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Andrews T. M., Goldthorp R., Watts R. W. Fluorimetric measurement of the phenylalanine content of human granulocytes. Clin Chim Acta. 1973 Feb 12;43(3):379–387. doi: 10.1016/0009-8981(73)90477-4. [DOI] [PubMed] [Google Scholar]
  2. Buse M. G., Reid S. S. Leucine. A possible regulator of protein turnover in muscle. J Clin Invest. 1975 Nov;56(5):1250–1261. doi: 10.1172/JCI108201. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Buse M. G., Weigand D. A. Studies concerning the specificity of the effect of leucine on the turnover of proteins in muscles of control and diabetic rats. Biochim Biophys Acta. 1977 Mar 2;475(1):81–89. doi: 10.1016/0005-2787(77)90341-0. [DOI] [PubMed] [Google Scholar]
  4. Chua B. H., Siehl D. L., Morgan H. E. A role for leucine in regulation of protein turnover in working rat hearts. Am J Physiol. 1980 Dec;239(6):E510–E514. doi: 10.1152/ajpendo.1980.239.6.E510. [DOI] [PubMed] [Google Scholar]
  5. Chua B., Siehl D. L., Morgan H. E. Effect of leucine and metabolites of branched chain amino acids on protein turnover in heart. J Biol Chem. 1979 Sep 10;254(17):8358–8362. [PubMed] [Google Scholar]
  6. Clark A. S., Mitch W. E. Comparison of protein synthesis and degradation in incubated and perfused muscle. Biochem J. 1983 Jun 15;212(3):649–653. doi: 10.1042/bj2120649. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Clark A. S., Mitch W. E. Muscle protein turnover and glucose uptake in acutely uremic rats. Effects of insulin and the duration of renal insufficiency. J Clin Invest. 1983 Sep;72(3):836–845. doi: 10.1172/JCI111054. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Fulks R. M., Li J. B., Goldberg A. L. Effects of insulin, glucose, and amino acids on protein turnover in rat diaphragm. J Biol Chem. 1975 Jan 10;250(1):290–298. [PubMed] [Google Scholar]
  9. Goldberg A. L., Martel S. B., Kushmerick M. J. In vitro preparations of the diaphragm and other skeletal muscles. Methods Enzymol. 1975;39:82–94. doi: 10.1016/s0076-6879(75)39012-5. [DOI] [PubMed] [Google Scholar]
  10. Li J. B., Jefferson L. S. Influence of amino acid availability on protein turnover in perfused skeletal muscle. Biochim Biophys Acta. 1978 Dec 1;544(2):351–359. doi: 10.1016/0304-4165(78)90103-4. [DOI] [PubMed] [Google Scholar]
  11. Libby P., Goldberg A. L. Effects of chymostatin and other proteinase inhibitors on protein breakdown and proteolytic activities in muscle. Biochem J. 1980 Apr 15;188(1):213–220. doi: 10.1042/bj1880213. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Lundholm K., Edström S., Ekman L., Karlberg I., Walker P., Scherstén T. Protein degradation in human skeletal muscle tissue: the effect of insulin, leucine, amino acids and ions. Clin Sci (Lond) 1981 Mar;60(3):319–326. doi: 10.1042/cs0600319. [DOI] [PubMed] [Google Scholar]
  13. Mitch W. E. Metabolism and metabolic effects of ketoacids. Am J Clin Nutr. 1980 Jul;33(7):1642–1648. doi: 10.1093/ajcn/33.7.1642. [DOI] [PubMed] [Google Scholar]
  14. Mitch W. E., Walser M., Sapir D. G. Nitrogen sparing induced by leucine compared with that induced by its keto analogue, alpha-ketoisocaproate, in fasting obese man. J Clin Invest. 1981 Feb;67(2):553–562. doi: 10.1172/JCI110066. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Morgan H. E., Earl D. C., Broadus A., Wolpert E. B., Giger K. E., Jefferson L. S. Regulation of protein synthesis in heart muscle. I. Effect of amino acid levels on protein synthesis. J Biol Chem. 1971 Apr 10;246(7):2152–2162. [PubMed] [Google Scholar]
  16. Odessey R., Goldberg A. L. Leucine degradation in cell-free extracts of skeletal muscle. Biochem J. 1979 Feb 15;178(2):475–489. doi: 10.1042/bj1780475. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Odessey R., Goldberg A. L. Oxidation of leucine by rat skeletal muscle. Am J Physiol. 1972 Dec;223(6):1376–1383. doi: 10.1152/ajplegacy.1972.223.6.1376. [DOI] [PubMed] [Google Scholar]
  18. Rannels D. E., Hjalmarson A. C., Morgan H. E. Effects of noncarbohydrate substrates on protein synthesis in muscle. Am J Physiol. 1974 Mar;226(3):528–539. doi: 10.1152/ajplegacy.1974.226.3.528. [DOI] [PubMed] [Google Scholar]
  19. Sapir D. G., Stewart P. M., Walser M., Moreadith C., Moyer E. D., Imbembo A. L., Rosenshein N. B., Munoz S. Effects of alpha-ketoisocaproate and of leucine on nitrogen metabolism in postoperative patients. Lancet. 1983 May 7;1(8332):1010–1014. doi: 10.1016/s0140-6736(83)92643-0. [DOI] [PubMed] [Google Scholar]
  20. Smith S. B., Briggs S., Triebwasser K. C., Freedland R. A. Re-evaluation of amino-oxyacetate as an inhibitor. Biochem J. 1977 Feb 15;162(2):453–455. doi: 10.1042/bj1620453. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Stewart P. M., Walser M., Drachman D. B. Branched-chain ketoacids reduce muscle protein degradation in Duchenne muscular dystrophy. Muscle Nerve. 1982 Mar;5(3):197–201. doi: 10.1002/mus.880050304. [DOI] [PubMed] [Google Scholar]
  22. Tischler M. E., Desautels M., Goldberg A. L. Does leucine, leucyl-tRNA, or some metabolite of leucine regulate protein synthesis and degradation in skeletal and cardiac muscle? J Biol Chem. 1982 Feb 25;257(4):1613–1621. [PubMed] [Google Scholar]
  23. Tischler M. E. Is regulation of proteolysis associated with redox-state changes in rat skeletal muscle? Biochem J. 1980 Dec 15;192(3):963–966. doi: 10.1042/bj1920963. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. WAALKES T. P., UDENFRIEND S. A fluorometric method for the estimation of tyrosine in plasma and tissues. J Lab Clin Med. 1957 Nov;50(5):733–736. [PubMed] [Google Scholar]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES