Skip to main content
NCBI home page
Biochemical Journal logoLink to Biochemical Journal
. 1967 Dec;105(3):953–963. doi: 10.1042/bj1050953

Carnitine and derivatives in rat tissues

D J Pearson 1,*, P K Tubbs 1
PMCID: PMC1198413  PMID: 16742571

Abstract

1. Free carnitine, acetylcarnitine, short-chain acylcarnitine and acid-insoluble carnitine (probably long-chain acylcarnitine) have been measured in rat tissues. 2. Starvation caused an increase in the proportion of carnitine that was acetylated in liver and kidney; at least in liver fat-feeding had the same effect, whereas a carbohydrate diet caused a very low acetylcarnitine content. 3. In heart, on the other hand, starvation did not cause an increase in the acetylcarnitine/carnitine ratio, whereas fat-feeding caused a decrease. The acetylcarnitine content of heart was diminished by alloxan-diabetes or a fatty diet, but not by re-feeding with carbohydrate. 4. Under conditions of increased fatty acid supply the acid-insoluble carnitine content was increased in heart, liver and kidney. 5. The acylation state of carnitine was capable of very rapid change. Concentrations of carnitine derivatives varied with different methods of obtaining tissue samples, and very little acid-insoluble carnitine was found in tissues of rats anaesthetized with Nembutal. In liver the acetylcarnitine (and acetyl-CoA) content decreased if freezing of tissue samples was delayed; in heart this caused an increase in acetylcarnitine. 6. Incubation of diaphragms with acetate or dl-β-hydroxybutyrate caused the acetylcarnitine content to become elevated. 7. Perfusion of hearts with fatty acids containing an even number of carbon atoms, dl-β-hydroxybutyrate or pyruvate resulted in increased contents of acetylcarnitine and acetyl-CoA. Accumulation of these acetyl compounds was prevented by the additional presence of propionate or pentanoate in the perfusion medium; this prevention was not due to extensive propionylation of CoA or carnitine. 8. Perfusion of hearts with palmitate caused a severalfold increase in the content of acid-insoluble carnitine; this increase did not occur when propionate was also present. 9. Comparison of the acetylation states of carnitine and CoA in perfused hearts suggests that the carnitine acetyltransferase reactants may remain near equilibrium despite wide variations in their steady-state concentrations. This is not the case with the citrate synthase reaction. It is suggested that the carnitine acetyltransferase system buffers the tissue content of acetyl-CoA against rapid changes.

Full text

PDF
953

Selected References

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

  1. BEENAKKERS A. M., KLINGENBERG M. CARNITINE-COENZYME A TRANSACETYLASE IN MITOCHONDRIA FROM VARIOUS ORGANS. Biochim Biophys Acta. 1964 Apr 20;84:205–207. doi: 10.1016/0926-6542(64)90081-2. [DOI] [PubMed] [Google Scholar]
  2. BREMER J. Carnitine in intermediary metabolism. Reversible acetylation of carnitine by mitochondria. J Biol Chem. 1962 Jul;237:2228–2231. [PubMed] [Google Scholar]
  3. BREMER J. Carnitine in intermediary metabolism. The metabolism of fatty acid esters of carnitine by mitochondria. J Biol Chem. 1962 Dec;237:3628–3632. [PubMed] [Google Scholar]
  4. BRESSLER R., KATZ R. I. THE EFFECT OF CARNITINE ON THE RATE OF INCORPORATION OF PRECURSORS INTO FATTY ACIDS. J Biol Chem. 1965 Feb;240:622–627. [PubMed] [Google Scholar]
  5. Bowman R. H. Effects of diabetes, fatty acids, and ketone bodies on tricarboxylic acid cycle metabolism in the perfused rat heart. J Biol Chem. 1966 Jul 10;241(13):3041–3048. [PubMed] [Google Scholar]
  6. CHASE J. F., PEARSON D. J., TUBBS P. K. THE PREPARATION OF CRYSTALLIN CARNITINE ACETYLTRANSFERASE. Biochim Biophys Acta. 1965 Jan;96:162–165. doi: 10.1016/0005-2787(65)90622-2. [DOI] [PubMed] [Google Scholar]
  7. Chase J. F. The substrate specificity of carnitine acetyltransferase. Biochem J. 1967 Aug;104(2):510–518. doi: 10.1042/bj1040510. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Childress C. C., Sacktor B., Traynor D. R. Function of carnitine in the fatty acid oxidase-deficient insect flight muscle. J Biol Chem. 1967 Feb 25;242(4):754–760. [PubMed] [Google Scholar]
  9. FLAVIN M., ORTIZ P. J., OCHOA S. Metabolism of propionic acid in animal tissues. Nature. 1955 Oct 29;176(4487):823–826. doi: 10.1038/176823a0. [DOI] [PubMed] [Google Scholar]
  10. FRAENKEL G., FRIEDMAN S. Carnitine. Vitam Horm. 1957;15:73–118. doi: 10.1016/s0083-6729(08)60508-7. [DOI] [PubMed] [Google Scholar]
  11. FRITZ I. B. Action of carnitine on long chain fatty acid oxidation by liver. Am J Physiol. 1959 Aug;197:297–304. doi: 10.1152/ajplegacy.1959.197.2.297. [DOI] [PubMed] [Google Scholar]
  12. FRITZ I. B., SCHULTZ S. K., SRERE P. A. Properties of partially purified carnitine acetyltransferase. J Biol Chem. 1963 Jul;238:2509–2517. [PubMed] [Google Scholar]
  13. FRITZ I. B., YUE K. T. LONG-CHAIN CARNITINE ACYLTRANSFERASE AND THE ROLE OF ACYLCARNITINE DERIVATIVES IN THE CATALYTIC INCREASE OF FATTY ACID OXIDATION INDUCED BY CARNITINE. J Lipid Res. 1963 Jul;4:279–288. [PubMed] [Google Scholar]
  14. FRITZ I. The effect of muscle extracts on the oxidation of palmitic acid by liver slices and homogenates. Acta Physiol Scand. 1955 Oct 12;34(4):367–385. doi: 10.1111/j.1748-1716.1955.tb01256.x. [DOI] [PubMed] [Google Scholar]
  15. GORDON R. S., Jr, CHERKES A. Production of unesterified fatty acids from isolated rat adipose tissue incubated in vitro. Proc Soc Exp Biol Med. 1958 Jan;97(1):150–151. doi: 10.3181/00379727-97-23672. [DOI] [PubMed] [Google Scholar]
  16. Garland P. B., Newsholme E. A., Randle P. J. Regulation of glucose uptake by muscle. 9. Effects of fatty acids and ketone bodies, and of alloxan-diabetes and starvation, on pyruvate metabolism and on lactate-pyruvate and L-glycerol 3-phosphate-dihydroxyacetone phosphate concentration ratios in rat heart and rat diaphragm muscles. Biochem J. 1964 Dec;93(3):665–678. doi: 10.1042/bj0930665. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Garland P. B., Randle P. J. Regulation of glucose uptake by muscles. 10. Effects of alloxan-diabetes, starvation, hypophysectomy and adrenalectomy, and of fatty acids, ketone bodies and pyruvate, on the glycerol output and concentrations of free fatty acids, long-chain fatty acyl-coenzyme A, glycerol phosphate and citrate-cycle intermediates in rat heart and diaphragm muscles. Biochem J. 1964 Dec;93(3):678–687. doi: 10.1042/bj0930678. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. HICKS R. M., KERLY M. Transaminase activity in the perfused rat heart. J Physiol. 1960 Mar;150:621–632. doi: 10.1113/jphysiol.1960.sp006408. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. HOHORST H. J., KREUTZ F. H., BUECHER T. [On the metabolite content and the metabolite concentration in the liver of the rat]. Biochem Z. 1959;332:18–46. [PubMed] [Google Scholar]
  20. Hales C. N., Kennedy G. C. Plasma glucose, non-esterified fatty acid and insulin concentrations in hypothalamic-hyperphagic rats. Biochem J. 1964 Mar;90(3):620–624. doi: 10.1042/bj0900620. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Hathaway J. A., Atkinson D. E. Kinetics of regulatory enzymes: effect of adenosine triphosphate on yeast citrate synthase. Biochem Biophys Res Commun. 1965 Sep 8;20(5):661–665. doi: 10.1016/0006-291x(65)90452-3. [DOI] [PubMed] [Google Scholar]
  22. LENG R. A., ANNISON E. F. Metabolism of acetate, propionate and butyrate by sheep-liver slices. Biochem J. 1963 Feb;86:319–327. doi: 10.1042/bj0860319. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. MAHLER H. R., WAKIL S. J., BOCK R. M. Studies on fatty acid oxidation. I. Enzymatic activation of fatty acids. J Biol Chem. 1953 Sep;204(1):453–468. [PubMed] [Google Scholar]
  24. MARQUIS N. R., FRITZ I. B. EFFECTS OF TESTOSTERONE ON THE DISTRIBUTION OF CARNITINE, ACETYLCARNITINE, AND CARNITINE ACETYLTRANSFERASE IN TISSUES OF THE REPRODUCTIVE SYSTEM OF THE MALE RAT. J Biol Chem. 1965 May;240:2197–2200. [PubMed] [Google Scholar]
  25. MARQUIS N. R., FRITZ I. B. THE DISTRIBUTION OF CARNITINE, ACETYLCARNITINE, AND CARNITINE ACETYLTRANSFERASE IN RAT TISSUES. J Biol Chem. 1965 May;240:2193–2196. [PubMed] [Google Scholar]
  26. MASORO E. J., FELTS J. M., PANAGOS S. S., RAPPORT D. The regulation of hepatic acetate-1-C14 metabolism by short-chain fatty acids. Arch Biochem Biophys. 1957 Jun;68(2):270–283. doi: 10.1016/0003-9861(57)90359-4. [DOI] [PubMed] [Google Scholar]
  27. MORGAN H. E., HENDERSON M. J., REGEN D. M., PARK C. R. Regulation of glucose uptake in muscle. I. The effects of insulin and anoxia on glucose transport and phosphorylation in the isolated, perfused heart of normal rats. J Biol Chem. 1961 Feb;236:253–261. [PubMed] [Google Scholar]
  28. Max S. R., Purvis J. L. Energy-linked incorporation of citrate into rat liver mitochondria. Biochem Biophys Res Commun. 1965 Dec 21;21(6):587–594. doi: 10.1016/0006-291x(65)90526-7. [DOI] [PubMed] [Google Scholar]
  29. NEWSHOLME E. A., RANDLE P. J. Regulation of glucose uptake by muscle. 5. Effects of anoxia, insulin, adrenaline and prolonged starving on concentrations of hexose phosphates in isolated rat diaphragm and perfused isolated rat heart. Biochem J. 1961 Sep;80:655–662. doi: 10.1042/bj0800655. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. NORUM K. R. PALMITYL-COA:CARNITINE PALMITYLTRANSFERASE. PURIFICATION FROM CALF-LIVER MITOCHONDRIA AND SOME PROPERTIES OF THE ENZYME. Biochim Biophys Acta. 1964 Jul 8;89:95–108. [PubMed] [Google Scholar]
  31. Newsholme E. A., Randle P. J. Regulation of glucose uptake by muscle. 7. Effects of fatty acids, ketone bodies and pyruvate, and of alloxan-diabetes, starvation, hypophysectomy and adrenalectomy, on the concentrations of hexose phosphates, nucleotides and inorganic phosphate in perfused rat heart. Biochem J. 1964 Dec;93(3):641–651. doi: 10.1042/bj0930641. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Norum K. R., Bremer J. The localization of acyl coenzyme A-carnitine acyltransferases in rat liver cells. J Biol Chem. 1967 Feb 10;242(3):407–411. [PubMed] [Google Scholar]
  33. Ontko J. A. Endogenous hepatic ketogenesis. Cofactor requirements. Biochim Biophys Acta. 1967 Feb 14;137(1):1–12. doi: 10.1016/0005-2760(67)90002-1. [DOI] [PubMed] [Google Scholar]
  34. PEARSON D. J., TUBBS P. K. ACETYL-CARNITINE IN HEART AND LIVER. Nature. 1964 Apr 4;202:91–91. doi: 10.1038/202091a0. [DOI] [PubMed] [Google Scholar]
  35. PEARSON D. J., TUBBS P. K. TISSUE LEVELS OF ACID-INSOLUBLE CARNITINE IN RAT HEART. Biochim Biophys Acta. 1964 Dec 2;84:772–773. doi: 10.1016/0926-6542(64)90042-3. [DOI] [PubMed] [Google Scholar]
  36. PENNINGTON R. J., APPLETON J. M. Further studies on the inhibition of acetate metabolism by propionate. Biochem J. 1958 May;69(1):119–125. doi: 10.1042/bj0690119. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. RANDLE P. J., SMITH G. H. Regulation of glucose uptake by muscle. 2. The effects of insulin, anaerobiosis and cell poisons on the penetration of isolated rat diaphragm by sugars. Biochem J. 1958 Nov;70(3):501–508. doi: 10.1042/bj0700501. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Randle P. J., Newsholme E. A., Garland P. B. Regulation of glucose uptake by muscle. 8. Effects of fatty acids, ketone bodies and pyruvate, and of alloxan-diabetes and starvation, on the uptake and metabolic fate of glucose in rat heart and diaphragm muscles. Biochem J. 1964 Dec;93(3):652–665. doi: 10.1042/bj0930652. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. SRERE P. A., KOSICKI G. W. The purification of citrate-condensing enzyme. J Biol Chem. 1961 Oct;236:2557–2559. [PubMed] [Google Scholar]
  40. STERN J. R., OCHOA S., LYNEN F. Enzymatic synthesis of citric acid. V. Reaction of acetyl coenzyme A. J Biol Chem. 1952 Sep;198(1):313–321. [PubMed] [Google Scholar]
  41. Shepherd D., Garland P. B. ATP controlled acetoacetate and citrate synthesis by rat liver mitochondria oxidising palmitoyl-carnitine, and the inhibition of citrate synthase by ATP. Biochem Biophys Res Commun. 1966 Jan 4;22(1):89–93. doi: 10.1016/0006-291x(66)90607-3. [DOI] [PubMed] [Google Scholar]
  42. TUBBS P. K. INHIBITION OF CITRATE FORMATION BY LONG-CHAIN ACYL THIOESTERS OF COENZYME A AS A POSSIBLE CONTROL MECHANISM IN FATTY ACID BIOSYNTHESIS. Biochim Biophys Acta. 1963 Oct 22;70:608–609. doi: 10.1016/0006-3002(63)90804-7. [DOI] [PubMed] [Google Scholar]
  43. Tubbs P. K., Garland P. B. Variations in tissue contents of coenzyme A thio esters and possible metabolic implications. Biochem J. 1964 Dec;93(3):550–557. doi: 10.1042/bj0930550. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. WIELAND O., WEISS L., EGER-NEUFELDT I. HEMMUNG DER ENZYMATISCHEN CITRONENSAEURESYNTHESE DURCH LANGKETTIGE ACYL-THIOESTER DES COENZYM A. Biochem Z. 1964 Jun 16;339:501–513. [PubMed] [Google Scholar]
  45. WOLLENBERGER A., RISTAU O., SCHOFFA G. [A simple technic for extremely rapid freezing of large pieces of tissue]. Pflugers Arch Gesamte Physiol Menschen Tiere. 1960;270:399–412. [PubMed] [Google Scholar]

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

RESOURCES