Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1988 Nov;82(5):1606–1613. doi: 10.1172/JCI113772

Regulation of leucine catabolism by caloric sources. Role of glucose and lipid in nitrogen sparing during nitrogen deprivation.

J A Vazquez 1, H S Paul 1, S A Adibi 1
PMCID: PMC442729  PMID: 3141479

Abstract

Previously we showed that hypocaloric amounts of glucose reduce leucine catabolism while an isocaloric amount of fat does not (1985. J. Clin. Invest. 76:737.). This study was designed to investigate whether the same difference exists when the entire caloric need is provided either as glucose or lipid. Rats were maintained for 3 d on total parenteral nutrition (350 cal/kg per d), after which the infusion of amino acids was discontinued and rats received the same amount of calories entirely as glucose or lipid for three more days. A third group of rats was infused with saline for 3 d. In comparison to glucose, lipid infusion resulted in higher urinary nitrogen excretion (55 +/- 3 vs. 37 +/- 2 mg N/24 h, P less than 0.05), muscle concentrations of tyrosine (95 +/- 8 vs. 42 +/- 8 microM, P less than 0.01), and leucine (168 +/- 19 vs. 84 +/- 16 microM, P less than 0.01), activity of BCKA dehydrogenase in muscle (2.2 +/- 0.2 vs. 1.4 +/- 0.04 nmol/mg protein per 30 min, P less than 0.05), and whole body rate of leucine oxidation (3.3 +/- 0.5 vs. 1.4 +/- 0.2 mumol/100 g per h, P less than 0.05). However, all these parameters were significantly lower in lipid-infused than starved rats. There was no significant difference between leucine incorporation into liver and muscle proteins of lipid and glucose-infused rats. On the other hand, starved rats showed a lower leucine incorporation into liver proteins. The data show that under conditions of adequate caloric intake lipid has an inhibitory effect on leucine catabolism but not as great as that of glucose. The mechanism of this difference may be related to a lesser inhibition of muscle protein degradation by lipid than glucose, thereby increasing the leucine pool, which in turn stimulates leucine oxidation.

Full text

PDF
1606

Images in this article

1610Image
on p.1610
1610Image
on p.1610
1610Image
on p.1610
1610Image
on p.1610

Selected References

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

  1. Adibi S. A. Interrelationships between level of amino acids in plasma and tissues during starvation. Am J Physiol. 1971 Sep;221(3):829–838. doi: 10.1152/ajplegacy.1971.221.3.829. [DOI] [PubMed] [Google Scholar]
  2. Adibi S. A. Metabolism of branched-chain amino acids in altered nutrition. Metabolism. 1976 Nov;25(11):1287–1302. doi: 10.1016/s0026-0495(76)80012-1. [DOI] [PubMed] [Google Scholar]
  3. Adibi S. A., Modesto T. A., Morse E. L., Amin P. M. Amino acid levels in plasma, liver, and skeletal muscle during protein deprivation. Am J Physiol. 1973 Aug;225(2):408–414. doi: 10.1152/ajplegacy.1973.225.2.408. [DOI] [PubMed] [Google Scholar]
  4. Adibi S. A., Morse E. L., Amin P. M. Role of insulin and glucose in the induction of hypoaminoacidemia in man: studies in normal, juvenile diabetic, and insuloma patients. J Lab Clin Med. 1975 Sep;86(3):395–409. [PubMed] [Google Scholar]
  5. Adibi S. A. Roles of branched-chain amino acids in metabolic regulation. J Lab Clin Med. 1980 Apr;95(4):475–484. [PubMed] [Google Scholar]
  6. Bates P. C., Millward D. J. Myofibrillar protein turnover. Synthesis rates of myofibrillar and sarcoplasmic protein fractions in different muscles and the changes observed during postnatal development and in response to feeding and starvation. Biochem J. 1983 Aug 15;214(2):587–592. doi: 10.1042/bj2140587. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Block K. P., Aftring R. P., Mehard W. B., Buse M. G. Modulation of rat skeletal muscle branched-chain alpha-keto acid dehydrogenase in vivo. Effects of dietary protein and meal consumption. J Clin Invest. 1987 May;79(5):1349–1358. doi: 10.1172/JCI112961. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Bremer J. Carnitine--metabolism and functions. Physiol Rev. 1983 Oct;63(4):1420–1480. doi: 10.1152/physrev.1983.63.4.1420. [DOI] [PubMed] [Google Scholar]
  9. Brennan M. F., Fitzpatrick G. F., Cohen K. H., Moore F. D. Glycerol: major contributor to the short term protein sparing effect of fat emulsions in normal man. Ann Surg. 1975 Oct;182(4):386–394. doi: 10.1097/00000658-197510000-00004. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. CHAPPELL J. B., PERRY S. V. Biochemical and osmotic properties of skeletal muscle mitochondria. Nature. 1954 Jun 5;173(4414):1094–1095. doi: 10.1038/1731094a0. [DOI] [PubMed] [Google Scholar]
  11. Cahill G. F., Jr Starvation in man. N Engl J Med. 1970 Mar 19;282(12):668–675. doi: 10.1056/NEJM197003192821209. [DOI] [PubMed] [Google Scholar]
  12. Cederblad G., Finnström O., Mårtensson J. Urinary excretion of carnitine and its derivatives in newborns. Biochem Med. 1982 Apr;27(2):260–265. doi: 10.1016/0006-2944(82)90029-1. [DOI] [PubMed] [Google Scholar]
  13. Elia M., Neale G., Livesey G. Alanine and glutamine release from the human forearm: effects of glucose administration. Clin Sci (Lond) 1985 Aug;69(2):123–133. doi: 10.1042/cs0690123. [DOI] [PubMed] [Google Scholar]
  14. Felig P. Amino acid metabolism in man. Annu Rev Biochem. 1975;44:933–955. doi: 10.1146/annurev.bi.44.070175.004441. [DOI] [PubMed] [Google Scholar]
  15. 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]
  16. GUROFF G., UNDENFRIEND S. The uptake of tyrosine by isolated rat diaphragm. J Biol Chem. 1960 Dec;235:3518–3522. [PubMed] [Google Scholar]
  17. Harper A. E., Miller R. H., Block K. P. Branched-chain amino acid metabolism. Annu Rev Nutr. 1984;4:409–454. doi: 10.1146/annurev.nu.04.070184.002205. [DOI] [PubMed] [Google Scholar]
  18. Harris R. A., Paxton R. Regulation of branched chain alpha-ketoacid dehydrogenase complex by phosphorylation-dephosphorylation. Minisymposium report. Fed Proc. 1985 Feb;44(2):305–315. [PubMed] [Google Scholar]
  19. Hutson S. M., Cree T. C., Harper A. E. Regulation of leucine and alpha-ketoisocaproate metabolism in skeletal muscle. J Biol Chem. 1978 Nov 25;253(22):8126–8133. [PubMed] [Google Scholar]
  20. Jeejee hoy K. N., Anderson G. H., Nakhooda A. F., Greenberg G. R., Sanderson I., Marliss E. B. Metabolic studies in total parenteral nutrition with lipid in man. Comparison with glucose. J Clin Invest. 1976 Jan;57(1):125–136. doi: 10.1172/JCI108252. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Jefferson L. S., Li J. B., Rannels S. R. Regulation by insulin of amino acid release and protein turnover in the perfused rat hemicorpus. J Biol Chem. 1977 Feb 25;252(4):1476–1483. [PubMed] [Google Scholar]
  22. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  23. Laurent B. C., Moldawer L. L., Young V. R., Bistrian B. R., Blackburn G. L. Whole-body leucine and muscle protein kinetics in rats fed varying protein intakes. Am J Physiol. 1984 May;246(5 Pt 1):E444–E451. doi: 10.1152/ajpendo.1984.246.5.E444. [DOI] [PubMed] [Google Scholar]
  24. Lowell B. B., Goodman M. N. Protein sparing in skeletal muscle during prolonged starvation. Dependence on lipid fuel availability. Diabetes. 1987 Jan;36(1):14–19. doi: 10.2337/diab.36.1.14. [DOI] [PubMed] [Google Scholar]
  25. Lowell B. B., Ruderman N. B., Goodman M. N. Evidence that lysosomes are not involved in the degradation of myofibrillar proteins in rat skeletal muscle. Biochem J. 1986 Feb 15;234(1):237–240. doi: 10.1042/bj2340237. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. MUNRO H. N. Carbohydrate and fat as factors in protein utilization and metabolism. Physiol Rev. 1951 Oct;31(4):449–488. doi: 10.1152/physrev.1951.31.4.449. [DOI] [PubMed] [Google Scholar]
  27. May M. E., Aftring R. P., Buse M. G. Mechanism of the stimulation of branched chain oxoacid oxidation in liver by carnitine. J Biol Chem. 1980 Sep 25;255(18):8394–8397. [PubMed] [Google Scholar]
  28. May M. E., Mancusi V. J., Aftring R. P., Buse M. G. Effects of diabetes on oxidative decarboxylation of branched-chain keto acids. Am J Physiol. 1980 Sep;239(3):E215–E222. doi: 10.1152/ajpendo.1980.239.3.E215. [DOI] [PubMed] [Google Scholar]
  29. Motil K. J., Matthews D. E., Bier D. M., Burke J. F., Munro H. N., Young V. R. Whole-body leucine and lysine metabolism: response to dietary protein intake in young men. Am J Physiol. 1981 Jun;240(6):E712–E721. doi: 10.1152/ajpendo.1981.240.6.E712. [DOI] [PubMed] [Google Scholar]
  30. Nair K. S., Ford G. C., Halliday D. Effect of intravenous insulin treatment on in vivo whole body leucine kinetics and oxygen consumption in insulin-deprived type I diabetic patients. Metabolism. 1987 May;36(5):491–495. doi: 10.1016/0026-0495(87)90049-7. [DOI] [PubMed] [Google Scholar]
  31. Nair K. S., Woolf P. D., Welle S. L., Matthews D. E. Leucine, glucose, and energy metabolism after 3 days of fasting in healthy human subjects. Am J Clin Nutr. 1987 Oct;46(4):557–562. doi: 10.1093/ajcn/46.4.557. [DOI] [PubMed] [Google Scholar]
  32. Nallathambi S. A., Goorin A. M., Adibi S. A. Hepatic and skeletal muscle transport of cycloleucine during starvation. Am J Physiol. 1972 Jul;223(1):13–19. doi: 10.1152/ajplegacy.1972.223.1.13. [DOI] [PubMed] [Google Scholar]
  33. Paul H. S., Adibi S. A. Effect of carnitine on branched-chain amino acid oxidation by liver and skeletal muscle. Am J Physiol. 1978 May;234(5):E494–E499. doi: 10.1152/ajpendo.1978.234.5.E494. [DOI] [PubMed] [Google Scholar]
  34. Paul H. S., Adibi S. A. Leucine oxidation and protein turnover in clofibrate-induced muscle protein degradation in rats. J Clin Invest. 1980 Jun;65(6):1285–1293. doi: 10.1172/JCI109791. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Paul H. S., Adibi S. A. Leucine oxidation in diabetes and starvation: effects of ketone bodies on branched-chain amino acid oxidation in vitro. Metabolism. 1978 Feb;27(2):185–200. doi: 10.1016/0026-0495(78)90164-6. [DOI] [PubMed] [Google Scholar]
  36. Paul H. S., Adibi S. A. Role of ATP in the regulation of branched-chain alpha-keto acid dehydrogenase activity in liver and muscle mitochondria of fed, fasted, and diabetic rats. J Biol Chem. 1982 May 10;257(9):4875–4881. [PubMed] [Google Scholar]
  37. Paxton R., Harris R. A. Regulation of branched-chain alpha-ketoacid dehydrogenase kinase. Arch Biochem Biophys. 1984 May 15;231(1):48–57. doi: 10.1016/0003-9861(84)90361-8. [DOI] [PubMed] [Google Scholar]
  38. Shinnick F. L., Harper A. E. Branched-chain amino acid oxidation by isolated rat tissue preparations. Biochim Biophys Acta. 1976 Jul 21;437(2):477–486. doi: 10.1016/0304-4165(76)90016-7. [DOI] [PubMed] [Google Scholar]
  39. Tessari P., Nissen S. L., Miles J. M., Haymond M. W. Inverse relationship of leucine flux and oxidation to free fatty acid availability in vivo. J Clin Invest. 1986 Feb;77(2):575–581. doi: 10.1172/JCI112339. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Tessari P., Nosadini R., Trevisan R., De Kreutzenberg S. V., Inchiostro S., Duner E., Biolo G., Marescotti M. C., Tiengo A., Crepaldi G. Defective suppression by insulin of leucine-carbon appearance and oxidation in type 1, insulin-dependent diabetes mellitus. Evidence for insulin resistance involving glucose and amino acid metabolism. J Clin Invest. 1986 Jun;77(6):1797–1804. doi: 10.1172/JCI112504. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Vazquez J. A., Morse E. L., Adibi S. A. Effect of dietary fat, carbohydrate, and protein on branched-chain amino acid catabolism during caloric restriction. J Clin Invest. 1985 Aug;76(2):737–743. doi: 10.1172/JCI112029. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Vazquez J. A., Paul H. S., Adibi S. A. Relation between plasma and tissue parameters of leucine metabolism in fed and starved rats. Am J Physiol. 1986 Jun;250(6 Pt 1):E615–E621. doi: 10.1152/ajpendo.1986.250.6.E615. [DOI] [PubMed] [Google Scholar]
  43. WILLIAMSON D. H., MELLANBY J., KREBS H. A. Enzymic determination of D(-)-beta-hydroxybutyric acid and acetoacetic acid in blood. Biochem J. 1962 Jan;82:90–96. doi: 10.1042/bj0820090. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Wagenmakers A. J., Schepens J. T., Veldhuizen J. A., Veerkamp J. H. The activity state of the branched-chain 2-oxo acid dehydrogenase complex in rat tissues. Biochem J. 1984 May 15;220(1):273–281. doi: 10.1042/bj2200273. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Walser M. Therapeutic aspects of branched-chain amino and keto acids. Clin Sci (Lond) 1984 Jan;66(1):1–15. doi: 10.1042/cs0660001. [DOI] [PubMed] [Google Scholar]
  46. Wassner S. J., Schlitzer J. L., Li J. B. A rapid, sensitive method for the determination of 3-methylhistidine levels in urine and plasma using high-pressure liquid chromatography. Anal Biochem. 1980 May 15;104(2):284–289. doi: 10.1016/0003-2697(80)90076-7. [DOI] [PubMed] [Google Scholar]
  47. Wohlhueter R. M., Harper A. E. Coinduction of rat liver branched chain alpha-keto acid dehydrogenase activities. J Biol Chem. 1970 May 10;245(9):2391–2401. [PubMed] [Google Scholar]
  48. Wolfe R. R., Shaw J. H., Jahoor F., Herndon D. N., Wolfe M. H. Response to glucose infusion in humans: role of changes in insulin concentration. Am J Physiol. 1986 Mar;250(3 Pt 1):E306–E311. doi: 10.1152/ajpendo.1986.250.3.E306. [DOI] [PubMed] [Google Scholar]
  49. Young V. R., Munro H. N. Ntau-methylhistidine (3-methylhistidine) and muscle protein turnover: an overview. Fed Proc. 1978 Jul;37(9):2291–2300. [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES