Skip to main content

Some NLM-NCBI services and products are experiencing heavy traffic, which may affect performance and availability. We apologize for the inconvenience and appreciate your patience. For assistance, please contact our Help Desk at info@ncbi.nlm.nih.gov.

The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1982 Feb;69(2):377–383. doi: 10.1172/JCI110461

beta-Hydroxy fatty acid production by ischemic rabbit heart.

K H Moore, A E Koen, F E Hull
PMCID: PMC370987  PMID: 6799549

Abstract

beta-Hydroxymyristate, -palmitate, and -stearate were produced by and accumulated in isolated rabbit heart when perfused ischemically for 2-10 min by the nonrecirculating langendorff technique with 0.75 mM palmitate and 0.16 mM albumin. Tissue fractionation into mitochondria and cytosol showed that by 2 min of ischemia 44% of beta-hydroxypalmitate and 38% beta-hydroxystearate was located in the cytosol; this percentage increased to greater than 50% by 5 min of ischemia. Lipid fractionation studies showed that by 10 min these two beta-hydroxy fatty acids were distributed approximately as 60% acylcarnitine, 20% acyl-coenzyme A (CoA), and 20% free fatty acids. All three chemical forms of beta-hydroxypalmitate were found in both the mitochondria and the cytosol. After 10 min of ischemia beta-hydroxypalmitoyl-CoA and beta-hydroxystearoyl-CoA constituted at least 16% of the incremental long-chain acyl-CoA, whereas beta-hydroxypalmitoylcarnitine and b-hydroxystearoylcarnitine constituted 8% of the incremental long-chain acylcarnitine. These data suggests that myocardial beta-hydroxyacyl-CoA oxidation is limited during ischemia. Substrate accumulates and is transferred to the cytosol where it accumulates primarily as beta-hydroxyacylcarnitine.

Full text

PDF
377

Selected References

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

  1. Allred J. B., Guy D. G. Determination of coenzyme A and acetyl CoA in tissue extracts. Anal Biochem. 1969 May;29(2):293–299. doi: 10.1016/0003-2697(69)90312-1. [DOI] [PubMed] [Google Scholar]
  2. BLIGH E. G., DYER W. J. A rapid method of total lipid extraction and purification. Can J Biochem Physiol. 1959 Aug;37(8):911–917. doi: 10.1139/o59-099. [DOI] [PubMed] [Google Scholar]
  3. Bremer J., Wojtczak A. B. Factors controlling the rate of fatty acid -oxidation in rat liver mitochondria. Biochim Biophys Acta. 1972 Dec 8;280(4):515–530. doi: 10.1016/0005-2760(72)90131-2. [DOI] [PubMed] [Google Scholar]
  4. Crass M. F., 3rd, McCaskill E. S., Shipp J. C. Effect of pressure development on glucose and palmitate metabolism in perfused heart. Am J Physiol. 1969 Jun;216(6):1569–1576. doi: 10.1152/ajplegacy.1969.216.6.1569. [DOI] [PubMed] [Google Scholar]
  5. Crass M. F., 3rd, Pieper G. M. Lipid and glycogen metabolism in the hypoxic heart: effects of epinephrine. Am J Physiol. 1975 Oct;229(4):885–889. doi: 10.1152/ajplegacy.1975.229.4.885. [DOI] [PubMed] [Google Scholar]
  6. Hull F. E., Radloff J. F., Sweeley C. C. beta-Hydroxy fatty acid production during fatty acid oxidation by heart mitochondria. Recent Adv Stud Cardiac Struct Metab. 1975;7:13–21. [PubMed] [Google Scholar]
  7. Idell-Wenger J. A., Grotyohann L. W., Neely J. R. Coenzyme A and carnitine distribution in normal and ischemic hearts. J Biol Chem. 1978 Jun 25;253(12):4310–4318. [PubMed] [Google Scholar]
  8. Kako K. J., Patterson S. D. Phosphatidate phosphohydrolase and palmitoyl-coenzyme A hydrolase in cardiac subcellular fractions of hyperthyroid rabbits and cardiomyopathic hamsters. Biochem J. 1975 Nov;152(2):313–323. doi: 10.1042/bj1520313. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Kurooka S., Hosoki K., Yoshimura Y. Some properties of long fatty acyl-coenzyme A thioesterase in rat organs. J Biochem. 1972 Apr;71(4):625–634. [PubMed] [Google Scholar]
  10. Lochner A., Kotzé J. C., Benade A. J., Gevers W. Mitochondrial oxidative phosphorylation in low-flow hypoxia: role of free fatty acids. J Mol Cell Cardiol. 1978 Sep;10(9):857–875. doi: 10.1016/0022-2828(78)90394-2. [DOI] [PubMed] [Google Scholar]
  11. Lopes-Cardozo M., Klazinga W., van den Bergh S. G. Accumulation of carnitine esters of beta-oxidation intermediates during palmitate oxidation by rat-liver mitochondria. Eur J Biochem. 1978 Feb;83(2):629–634. doi: 10.1111/j.1432-1033.1978.tb12132.x. [DOI] [PubMed] [Google Scholar]
  12. Mancha M., Stokes G. B., Stumpf P. K. Fat metabolism in higher plants. The determination of acyl-acyl carrier protein and acyl coenzyme A in a complex lipid mixture 1,2. Anal Biochem. 1975 Oct;68(2):600–608. doi: 10.1016/0003-2697(75)90655-7. [DOI] [PubMed] [Google Scholar]
  13. Matlib M. A., Rebman D., Ashraf M., Rouslin W., Schwartz A. Differential activities of putative subsarcolemmal and interfibrillar mitochondria from cardiac muscle. J Mol Cell Cardiol. 1981 Feb;13(2):163–170. doi: 10.1016/0022-2828(81)90213-3. [DOI] [PubMed] [Google Scholar]
  14. McGarry J. D., Foster D. W. An improved and simplified radioisotopic assay for the determination of free and esterified carnitine. J Lipid Res. 1976 May;17(3):277–281. [PubMed] [Google Scholar]
  15. Moore K. H., Radloff J. F., Hull F. E., Sweeley C. C. Incomplete fatty acid oxidation by ischemic heart: beta-hydroxy fatty acid production. Am J Physiol. 1980 Aug;239(2):H257–H265. doi: 10.1152/ajpheart.1980.239.2.H257. [DOI] [PubMed] [Google Scholar]
  16. Neely J. R., Rovetto M. J., Whitmer J. T. Rate-limiting steps of carbohydrate and fatty acid metabolism in ischemic hearts. Acta Med Scand Suppl. 1976;587:9–15. doi: 10.1111/j.0954-6820.1976.tb05861.x. [DOI] [PubMed] [Google Scholar]
  17. Oram J. F., Bennetch S. L., Neely J. R. Regulation of fatty acid utilization in isolated perfused rat hearts. J Biol Chem. 1973 Aug 10;248(15):5299–5309. [PubMed] [Google Scholar]
  18. Palmer J. W., Tandler B., Hoppel C. L. Biochemical properties of subsarcolemmal and interfibrillar mitochondria isolated from rat cardiac muscle. J Biol Chem. 1977 Dec 10;252(23):8731–8739. [PubMed] [Google Scholar]
  19. Pande S. V. On rate-controlling factors of long chain fatty acid oxidation. J Biol Chem. 1971 Sep 10;246(17):5384–5390. [PubMed] [Google Scholar]
  20. Shug A. L., Shrago E., Bittar N., Folts J. D., Koke J. R. Acyl-CoA inhibition of adenine nucleotide translocation in ischemic myocardium. Am J Physiol. 1975 Mar;228(3):689–692. doi: 10.1152/ajplegacy.1975.228.3.689. [DOI] [PubMed] [Google Scholar]
  21. Sobel B. E., Corr P. B., Robison A. K., Goldstein R. A., Witkowski F. X., Klein M. S. Accumulation of lysophosphoglycerides with arrhythmogenic properties in ischemic myocardium. J Clin Invest. 1978 Sep;62(3):546–553. doi: 10.1172/JCI109159. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Sordahl L. A., Schwartz A. Effects of dipyridamole on heart muscle mitochondria. Mol Pharmacol. 1967 Nov;3(6):509–515. [PubMed] [Google Scholar]
  23. 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]
  24. Veloso D., Veech R. L. Stoichiometric hydrolysis of long chain acyl-CoA and measurement of the CoA formed with an enzymatic cycling method. Anal Biochem. 1974 Dec;62(2):449–450. doi: 10.1016/0003-2697(74)90177-8. [DOI] [PubMed] [Google Scholar]
  25. Whitmer J. T., Idell-Wenger J. A., Rovetto M. J., Neely J. R. Control of fatty acid metabolism in ischemic and hypoxic hearts. J Biol Chem. 1978 Jun 25;253(12):4305–4309. [PubMed] [Google Scholar]
  26. Wood J. M., Bush B., Pitts B. J., Schwartz A. Inhibition of bovine heart Na+, K+-ATPase by palmitylcarnitine and palmityl-CoA. Biochem Biophys Res Commun. 1977 Jan 24;74(2):677–684. doi: 10.1016/0006-291x(77)90356-4. [DOI] [PubMed] [Google Scholar]
  27. Wood J. M., Wallick E. T., Schwartz A., Chang C. H. The effect of palmitoyl-coenzyme A on rat heart and liver mitochondria. Oxygen consumption and palmitoylcarnitine formation. Biochim Biophys Acta. 1977 Feb 23;486(2):331–340. doi: 10.1016/0005-2760(77)90029-7. [DOI] [PubMed] [Google Scholar]

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

RESOURCES