Skip to main content
NCBI home page
Biochemical Journal logoLink to Biochemical Journal
. 1995 Jan 15;305(Pt 2):591–597. doi: 10.1042/bj3050591

Effects of tetradecylthiopropionic acid and tetradecylthioacrylic acid on rat liver lipid metabolism.

S Skrede 1, P Wu 1, H Osmundsen 1
PMCID: PMC1136403  PMID: 7832778

Abstract

Studies of effects of 4-thia-substituted fatty acid analogues on rat liver lipid metabolism are described. With isolated hepatocytes tetradecylthiopropionate was shown to divert [1-14C]oleate from beta-oxidation into esterification, the total amount of [1-14C]oleate metabolized remaining unchanged. Tetradecylthiopropionyl-CoA was a good substrate for mitochondrial carnitine palmitoyltransferases I and II (EC 2.3.1.21), acyl-CoA oxidase (EC 1.3.3.6), for the microsomal (but not mitochondrial) glycerophosphate acyltransferase (EC 2.3.1.15), and for long-chain acyl-CoA dehydrogenase (EC 1.3.99.3). In isolated hepatocytes, its 4-thia-trans-2-enoic derivative, tetradecylthioacrylate, inhibits both beta-oxidation of, and incorporation of, [1-14C]oleate into lipids. In rat liver mitochondria tetradecylthiocrylate inhibited beta-oxidation. The degree of inhibition was not markedly increased by preincubation with tetradecylthioacrylate. Tetradecylthioacrylyl-CoA was a poor substrate for carnitine palmitoyltransferase I, and inhibited carnitine palmitoyltransferase II, microsomal glycerophosphate acyltransferase and acyl-CoA oxidase. It is concluded that the inhibitory effects of tetradecylthiopropionyl-CoA are expressed intramitochondrially, whereas primary sites of inhibition by tetradecylthioacrylyl-CoA are extramitochondrial.

Full text

PDF
591

Selected References

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

  1. Aarsland A., Aarsaether N., Bremer J., Berge R. K. Alkylthioacetic acids (3-thia fatty acids) as non-beta-oxidizable fatty acid analogues: a new group of hypolipidemic drugs. III. Dissociation of cholesterol- and triglyceride-lowering effects and the induction of peroxisomal beta-oxidation. J Lipid Res. 1989 Nov;30(11):1711–1718. [PubMed] [Google Scholar]
  2. Aarsland A., Berge R. K. Peroxisome proliferating sulphur- and oxy-substituted fatty acid analogues are activated to acyl coenzyme A thioesters. Biochem Pharmacol. 1991 Jan 1;41(1):53–61. doi: 10.1016/0006-2952(91)90010-3. [DOI] [PubMed] [Google Scholar]
  3. Bergseth S., Lund H., Poisson J. P., Bremer J., Davis-Van Thienen W., Davis E. J. Carnitine palmitoyltransferase: activation and inactivation in liver mitochondria from fed, fasted, hypo- and hyperthyroid rats. Biochim Biophys Acta. 1986 May 21;876(3):551–558. doi: 10.1016/0005-2760(86)90043-3. [DOI] [PubMed] [Google Scholar]
  4. Berry M. N., Friend D. S. High-yield preparation of isolated rat liver parenchymal cells: a biochemical and fine structural study. J Cell Biol. 1969 Dec;43(3):506–520. doi: 10.1083/jcb.43.3.506. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bremer J. The effect of fasting on the activity of liver carnitine palmitoyltransferase and its inhibition by malonyl-CoA. Biochim Biophys Acta. 1981 Sep 24;665(3):628–631. doi: 10.1016/0005-2760(81)90282-4. [DOI] [PubMed] [Google Scholar]
  6. Christiansen E. N., Davis E. J. The effects of coenzyme A and carnitine on steady-state ATP/ADP ratios and the rate of long-chain free fatty acid oxidation in liver mitochondria. Biochim Biophys Acta. 1978 Apr 11;502(1):17–28. doi: 10.1016/0005-2728(78)90127-5. [DOI] [PubMed] [Google Scholar]
  7. Daae L. N. The mitochondrial acylation of glycerophosphate in rat liver: fatty acid and positional specificity. Biochim Biophys Acta. 1972 May 23;270(1):23–31. doi: 10.1016/0005-2760(72)90173-7. [DOI] [PubMed] [Google Scholar]
  8. Dommes V., Kunau W. H. A convenient assay for acyl-CoA-dehydrogenases. Anal Biochem. 1976 Apr;71(2):571–578. doi: 10.1016/s0003-2697(76)80026-7. [DOI] [PubMed] [Google Scholar]
  9. Hovik R., Osmundsen H., Berge R., Aarsland A., Bergseth S., Bremer J. Effects of thia-substituted fatty acids on mitochondrial and peroxisomal beta-oxidation. Studies in vivo and in vitro. Biochem J. 1990 Aug 15;270(1):167–173. doi: 10.1042/bj2700167. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hvattum E., Bergseth S., Pedersen C. N., Bremer J., Aarsland A., Berge R. K. Microsomal oxidation of dodecylthioacetic acid (a 3-thia fatty acid) in rat liver. 1991 Mar 15-Apr 1Biochem Pharmacol. 41(6-7):945–953. doi: 10.1016/0006-2952(91)90200-o. [DOI] [PubMed] [Google Scholar]
  11. Hvattum E., Skrede S., Bremer J., Solbakken M. The metabolism of tetradecylthiopropionic acid, a 4-thia stearic acid, in the rat. In vivo and in vitro studies. Biochem J. 1992 Sep 15;286(Pt 3):879–887. doi: 10.1042/bj2860879. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. 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]
  13. Lau S. M., Brantley R. K., Thorpe C. 4-Thia-trans-2-alkenoyl-CoA derivatives: properties and enzymatic reactions. Biochemistry. 1989 Oct 3;28(20):8255–8262. doi: 10.1021/bi00446a043. [DOI] [PubMed] [Google Scholar]
  14. Mahadevan S., Malaiyandi M., Erfle J. D., Sauer F. Metabolism of L-carnitine esters of beta-substituted palmitic acid by rat liver mitochondria. J Biol Chem. 1970 Jun;245(12):3218–3224. [PubMed] [Google Scholar]
  15. Osmundsen H., Neat C. E., Norum K. R. Peroxisomal oxidation of long chain fatty acids. FEBS Lett. 1979 Mar 15;99(2):292–296. doi: 10.1016/0014-5793(79)80975-8. [DOI] [PubMed] [Google Scholar]
  16. Seglen P. O. Preparation of rat liver cells. 3. Enzymatic requirements for tissue dispersion. Exp Cell Res. 1973 Dec;82(2):391–398. doi: 10.1016/0014-4827(73)90357-1. [DOI] [PubMed] [Google Scholar]
  17. Skrede S., Bremer J. Acylcarnitine formation and fatty acid oxidation in hepatocytes from rats treated with tetradecylthioacetic acid (a 3-thia fatty acid). Biochim Biophys Acta. 1993 Apr 7;1167(2):189–196. doi: 10.1016/0005-2760(93)90161-2. [DOI] [PubMed] [Google Scholar]
  18. Small G. M., Burdett K., Connock M. J. A sensitive spectrophotometric assay for peroxisomal acyl-CoA oxidase. Biochem J. 1985 Apr 1;227(1):205–210. doi: 10.1042/bj2270205. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Sooranna S. R., Saggerson E. D. Interactions of insulin and adrenaline with glycerol phosphate acylation processes in fat-cells from rat. FEBS Lett. 1976 Apr 15;64(1):36–39. doi: 10.1016/0014-5793(76)80242-6. [DOI] [PubMed] [Google Scholar]
  20. Spydevold O., Bremer J. Induction of peroxisomal beta-oxidation in 7800 C1 Morris hepatoma cells in steady state by fatty acids and fatty acid analogues. Biochim Biophys Acta. 1989 May 15;1003(1):72–79. doi: 10.1016/0005-2760(89)90101-x. [DOI] [PubMed] [Google Scholar]
  21. Stanley K. K., Tubbs P. K. The role of intermediates in mitochondrial fatty acid oxidation. Biochem J. 1975 Jul;150(1):77–88. doi: 10.1042/bj1500077. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Stokke O., Bremer J. A simple method for preparation of methyl-labelled (-) carnitine. Biochim Biophys Acta. 1970 Dec 15;218(3):552–554. doi: 10.1016/0005-2760(70)90021-4. [DOI] [PubMed] [Google Scholar]
  23. Woldegiorgis G., Spennetta T., Corkey B. E., Williamson J. R., Shrago E. Extraction of tissue long-chain acyl-CoA esters and measurement by reverse-phase high-performance liquid chromatography. Anal Biochem. 1985 Oct;150(1):8–12. doi: 10.1016/0003-2697(85)90434-8. [DOI] [PubMed] [Google Scholar]
  24. Wu P., Skrede S., Hvattum E., Bremer J. Substrate and hormone regulation of palmitoyl-CoA synthetase in 7800 C1 Morris hepatoma cells and cultured rat hepatocytes. Biochim Biophys Acta. 1993 Oct 13;1170(2):118–124. doi: 10.1016/0005-2760(93)90060-m. [DOI] [PubMed] [Google Scholar]
  25. Yamashita S., Numa S. Partial purification and properties of glycerophosphate acyltransferase from rat liver. Formation of 1-acylglycerol 3-phosphate from sn-glycerol 3-phosphate and palmityl coenzyme A. Eur J Biochem. 1972 Dec 18;31(3):565–573. doi: 10.1111/j.1432-1033.1972.tb02566.x. [DOI] [PubMed] [Google Scholar]

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

RESOURCES