• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of biochemjBJ Latest papers and much more!
Biochem J. Oct 1, 1993; 295(Pt 1): 61–66.
PMCID: PMC1134820

Malonyl-CoA metabolism in cardiac myocytes and its relevance to the control of fatty acid oxidation.

Abstract

1. Viable myocytes were obtained from rat hearts. Oxidation of [1-14C]palmitate by these cells could be decreased by the addition of glucose (5 mM) or lactate (2 mM). In the presence of glucose, insulin decreased and adrenaline increased palmitate oxidation. 2. The myocytes contained activities of ATP citrate-lyase, acetyl-CoA carboxylase and the condensing enzyme of the fatty acid elongation system. No fatty acid synthase activity was demonstrable in myocytes. 3. In rat hearts perfused with 5 mM glucose, malonyl-CoA content was acutely raised by insulin. In the presence of glucose+insulin, perfusion with palmitate or adrenaline decreased the malonyl-CoA content. 4. It is concluded that malonyl-CoA can be synthesized within cardiac myocytes and that the level of this metabolite can be acutely regulated. This is likely to have consequences for the regulation of carnitine palmitoyltransferase in the heart.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.2M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Allison SP, Chamberlain MJ, Hinton P. Intravenous glucose tolerance, insulin, glucose, and free fatty acid levels after myocardial infarction. Br Med J. 1969 Dec 27;4(5686):776–778. [PMC free article] [PubMed]
  • Opie LH. Metabolism of free fatty acids, glucose and catecholamines in acute myocardial infarction. Relation to myocardial ischemia and infarct size. Am J Cardiol. 1975 Dec;36(7):938–953. [PubMed]
  • Kurien VA, Oliver MF. Serum-free-fatty-acids after acute myocardial infarction and cerebral vascular occlusion. Lancet. 1966 Jul 16;2(7455):122–127. [PubMed]
  • RANDLE PJ, GARLAND PB, HALES CN, NEWSHOLME EA. The glucose fatty-acid cycle. Its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus. Lancet. 1963 Apr 13;1(7285):785–789. [PubMed]
  • Lopaschuk GD, Spafford MA, Davies NJ, Wall SR. Glucose and palmitate oxidation in isolated working rat hearts reperfused after a period of transient global ischemia. Circ Res. 1990 Feb;66(2):546–553. [PubMed]
  • Caterson ID, Fuller SJ, Randle PJ. Effect of the fatty acid oxidation inhibitor 2-tetradecylglycidic acid on pyruvate dehydrogenase complex activity in starved and alloxan-diabetic rats. Biochem J. 1982 Oct 15;208(1):53–60. [PMC free article] [PubMed]
  • Hirche H, Langohr HD. Hemmung der Milchsäureaufnahme im Herzmuskel narkotisierter Hunde durch hohe arterielle Konzentration der freien Fettsäuren. Pflugers Arch Gesamte Physiol Menschen Tiere. 1967;293(3):208–214. [PubMed]
  • Spitzer JJ. Effect of lactate infusion on canine myocardial free fatty acid metabolism in vivo. Am J Physiol. 1974 Jan;226(1):213–217. [PubMed]
  • Spitzer JJ, Spitzer JA. Myocardial metabolism in dogs during hemorrhagic shock. Am J Physiol. 1972 Jan;222(1):101–105. [PubMed]
  • Bielefeld DR, Vary TC, Neely JR. Inhibition of carnitine palmitoyl-CoA transferase activity and fatty acid oxidation by lactate and oxfenicine in cardiac muscle. J Mol Cell Cardiol. 1985 Jun;17(6):619–625. [PubMed]
  • Forsey RG, Reid K, Brosnan JT. Competition between fatty acids and carbohydrate or ketone bodies as metabolic fuels for the isolated perfused heart. Can J Physiol Pharmacol. 1987 Mar;65(3):401–406. [PubMed]
  • Liu MS, Spitzer JJ. Oxidation of palmitate and lactate by beating myocytes isolated from adult dog heart. J Mol Cell Cardiol. 1978 May;10(5):415–426. [PubMed]
  • Montini J, Bagby GJ, Spitzer JJ. Importance of exogenous substrates for the energy production of adult rat heart myocytes. J Mol Cell Cardiol. 1981 Oct;13(10):903–911. [PubMed]
  • Taegtmeyer H, Hems R, Krebs HA. Utilization of energy-providing substrates in the isolated working rat heart. Biochem J. 1980 Mar 15;186(3):701–711. [PMC free article] [PubMed]
  • Chen V, Bagby GJ, Spitzer JJ. Exogenous substrate utilization by isolated myocytes from chronically diabetic rats. Am J Physiol. 1983 Jul;245(1):C46–C51. [PubMed]
  • Paulson DJ, Noonan JJ, Ward KM, Stanley H, Sherratt A, Shug AL. Effects of POCA on metabolism and function in the ischemic rat heart. Basic Res Cardiol. 1986 Mar-Apr;81(2):180–187. [PubMed]
  • Molaparast-Saless F, Liedtke AJ, Nellis SH. Effects of the fatty acid blocking agents, oxfenicine and 4-bromocrotonic acid, on performance in aerobic and ischemic myocardium. J Mol Cell Cardiol. 1987 May;19(5):509–520. [PubMed]
  • Higgins AJ, Morville M, Burges RA, Gardiner DG, Page MG, Blackburn KJ. Oxfenicine diverts rat muscle metabolism from fatty acid to carbohydrate oxidation and protects the ischaemic rat heart. Life Sci. 1980 Sep 15;27(11):963–970. [PubMed]
  • Liedtke AJ, Nellis SH, Mjøs OD. Effects of reducing fatty acid metabolism on mechanical function in regionally ischemic hearts. Am J Physiol. 1984 Sep;247(3 Pt 2):H387–H394. [PubMed]
  • Miller WP, Liedtke AJ, Nellis SH. Effects of 2-tetradecylglycidic acid on myocardial function in swine hearts. Am J Physiol. 1986 Sep;251(3 Pt 2):H547–H553. [PubMed]
  • Lopaschuk GD, Wall SR, Olley PM, Davies NJ. Etomoxir, a carnitine palmitoyltransferase I inhibitor, protects hearts from fatty acid-induced ischemic injury independent of changes in long chain acylcarnitine. Circ Res. 1988 Dec;63(6):1036–1043. [PubMed]
  • McGarry JD, Foster DW. Regulation of hepatic fatty acid oxidation and ketone body production. Annu Rev Biochem. 1980;49:395–420. [PubMed]
  • McGarry JD, Sen A, Esser V, Woeltje KF, Weis B, Foster DW. New insights into the mitochondrial carnitine palmitoyltransferase enzyme system. Biochimie. 1991 Jan;73(1):77–84. [PubMed]
  • Saggerson D, Ghadiminejad I, Awan M. Regulation of mitochondrial carnitine palmitoyl transferases from liver and extrahepatic tissues. Adv Enzyme Regul. 1992;32:285–306. [PubMed]
  • Woeltje KF, Esser V, Weis BC, Cox WF, Schroeder JG, Liao ST, Foster DW, McGarry JD. Inter-tissue and inter-species characteristics of the mitochondrial carnitine palmitoyltransferase enzyme system. J Biol Chem. 1990 Jun 25;265(18):10714–10719. [PubMed]
  • Kolodziej MP, Crilly PJ, Corstorphine CG, Zammit VA. Development and characterization of a polyclonal antibody against rat liver mitochondrial overt carnitine palmitoyltransferase (CPT I). Distinction of CPT I from CPT II and of isoforms of CPT I in different tissues. Biochem J. 1992 Mar 1;282(Pt 2):415–421. [PMC free article] [PubMed]
  • Saggerson ED, Carpenter CA. Carnitine palmitoyltransferase and carnitine octanoyltransferase activities in liver, kidney cortex, adipocyte, lactating mammary gland, skeletal muscle and heart. FEBS Lett. 1981 Jul 6;129(2):229–232. [PubMed]
  • Bird MI, Saggerson ED. Binding of malonyl-CoA to isolated mitochondria. Evidence for high- and low-affinity sites in liver and heart and relationship to inhibition of carnitine palmitoyltransferase activity. Biochem J. 1984 Sep 15;222(3):639–647. [PMC free article] [PubMed]
  • Edwards MR, Bird MI, Saggerson ED. Effects of DL-2-bromopalmitoyl-CoA and bromoacetyl-CoA in rat liver and heart mitochondria. Inhibition of carnitine palmitoyltransferase and displacement of [14C]malonyl-CoA from mitochondrial binding sites. Biochem J. 1985 Aug 15;230(1):169–179. [PMC free article] [PubMed]
  • Thampy KG. Formation of malonyl coenzyme A in rat heart. Identification and purification of an isozyme of A carboxylase from rat heart. J Biol Chem. 1989 Oct 25;264(30):17631–17634. [PubMed]
  • Bianchi A, Evans JL, Iverson AJ, Nordlund AC, Watts TD, Witters LA. Identification of an isozymic form of acetyl-CoA carboxylase. J Biol Chem. 1990 Jan 25;265(3):1502–1509. [PubMed]
  • McGarry JD, Mills SE, Long CS, Foster DW. Observations on the affinity for carnitine, and malonyl-CoA sensitivity, of carnitine palmitoyltransferase I in animal and human tissues. Demonstration of the presence of malonyl-CoA in non-hepatic tissues of the rat. Biochem J. 1983 Jul 15;214(1):21–28. [PMC free article] [PubMed]
  • EVANS WH, MUELLER PS. EFFECTS OF PALMITATE ON THE METABOLISM OF LEUKOCYTES FROM GUINEA PIG EXUDATE. J Lipid Res. 1963 Jan;4:39–45. [PubMed]
  • ITAYA K, UI M. COLORIMETRIC DETERMINATION OF FREE FATTY ACIDS IN BIOLOGICAL FLUIDS. J Lipid Res. 1965 Jan;6:16–20. [PubMed]
  • Powell T, Terrar DA, Twist VW. Electrical properties of individual cells isolated from adult rat ventricular myocardium. J Physiol. 1980 May;302:131–153. [PMC free article] [PubMed]
  • Mowbray J, Ottaway JH. The flux of pyruvate in perfused rat heart. Eur J Biochem. 1973 Jul 16;36(2):362–368. [PubMed]
  • 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]
  • McGarry JD, Stark MJ, Foster DW. Hepatic malonyl-CoA levels of fed, fasted and diabetic rats as measured using a simple radioisotopic assay. J Biol Chem. 1978 Nov 25;253(22):8291–8293. [PubMed]
  • Allred JB, Guy DG. Determination of coenzyme A and acetyl CoA in tissue extracts. Anal Biochem. 1969 May;29(2):293–299. [PubMed]
  • Cederblad G, Lindstedt S. A method for the determination of carnitine in the picomole range. Clin Chim Acta. 1972 Mar;37:235–243. [PubMed]
  • Holland R, Witters LA, Hardie DG. Glucagon inhibits fatty acid synthesis in isolated hepatocytes via phosphorylation of acetyl-CoA carboxylase by cyclic-AMP-dependent protein kinase. Eur J Biochem. 1984 Apr 16;140(2):325–333. [PubMed]
  • Saggerson ED, Greenbaum AL. The regulation of triglyceride synthesis and fatty acid synthesis in rat epididymal adipose tissue. Effects of altered dietary and hormonal conditions. Biochem J. 1970 Sep;119(2):221–242. [PMC free article] [PubMed]
  • Carey EM, Dils R. Fatty acid biosynthesis. V. Purification and characterisation of fatty acid synthetase from lactating-rabbit mammary gland. Biochim Biophys Acta. 1970 Sep 8;210(3):371–387. [PubMed]
  • Prasad MR, Cinti DL. Effect of the peroxisomal proliferator di(2-ethylhexyl)phthalate on component reactions of the rat hepatic microsomal fatty acid chain elongation system and on other hepatic lipogenic enzymes. Arch Biochem Biophys. 1986 Aug 1;248(2):479–488. [PubMed]
  • Martin BR, Denton RM. The intracellular localization of enzymes in white-adipose-tissue fat-cells and permeability properties of fat-cell mitochondria. Transfer of acetyl units and reducing power between mitochondria and cytoplasm. Biochem J. 1970 May;117(5):861–877. [PMC free article] [PubMed]
  • Saggerson ED. Lipogenesis in rat and guinea-pig isolated epididymal fat-cells. Biochem J. 1974 May;140(2):211–224. [PMC free article] [PubMed]
  • PHILLIPS AH, LANGDON RG. Hepatic triphosphopyridine nucleotide-cytochrome c reductase: isolation, characterization, and kinetic studies. J Biol Chem. 1962 Aug;237:2652–2660. [PubMed]
  • Sottocasa GL, Kuylenstierna B, Ernster L, Bergstrand A. An electron-transport system associated with the outer membrane of liver mitochondria. A biochemical and morphological study. J Cell Biol. 1967 Feb;32(2):415–438. [PMC free article] [PubMed]
  • Switzer BR, Summer GK. A modified fluorometric micromethod for DNA. Clin Chim Acta. 1971 Apr;32(2):203–206. [PubMed]
  • LOWRY OH, ROSEBROUGH NJ, FARR AL, RANDALL RJ. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed]
  • Denton RM, McCormack JG. Ca2+ as a second messenger within mitochondria of the heart and other tissues. Annu Rev Physiol. 1990;52:451–466. [PubMed]
  • Jamil H, Madsen NB. Phosphorylation state of acetyl-coenzyme A carboxylase. I. Linear inverse relationship to activity ratios at different citrate concentrations. J Biol Chem. 1987 Jan 15;262(2):630–637. [PubMed]
  • Scholte HR, Luyt-Houwen IE, Dubelaar ML, Hulsmann WC. The source of malonyl-CoA in rat heart. The calcium paradox releases acetyl-CoA carboxylase and not propionyl-CoA carboxylase. FEBS Lett. 1986 Mar 17;198(1):47–50. [PubMed]
  • Wit-Peeters EM, Scholte HR, Elenbaas HL. Fatty acid synthesis in heart. Biochim Biophys Acta. 1970 Sep 8;210(3):360–370. [PubMed]
  • Saggerson D. Carnitine palmitoyltransferase in extrahepatic tissues. Biochem Soc Trans. 1986 Aug;14(4):679–681. [PubMed]
  • Thampy KG, Wakil SJ. Regulation of acetyl-coenzyme A carboxylase. I. Purification and properties of two forms of acetyl-coenzyme A carboxylase from rat liver. J Biol Chem. 1988 May 5;263(13):6447–6453. [PubMed]
  • Kim KH, López-Casillas F, Bai DH, Luo X, Pape ME. Role of reversible phosphorylation of acetyl-CoA carboxylase in long-chain fatty acid synthesis. FASEB J. 1989 Sep;3(11):2250–2256. [PubMed]
  • Haystead TA, Moore F, Cohen P, Hardie DG. Roles of the AMP-activated and cyclic-AMP-dependent protein kinases in the adrenaline-induced inactivation of acetyl-CoA carboxylase in rat adipocytes. Eur J Biochem. 1990 Jan 12;187(1):199–205. [PubMed]
  • Mabrouk GM, Helmy IM, Thampy KG, Wakil SJ. Acute hormonal control of acetyl-CoA carboxylase. The roles of insulin, glucagon, and epinephrine. J Biol Chem. 1990 Apr 15;265(11):6330–6338. [PubMed]
  • Witters LA, Kemp BE. Insulin activation of acetyl-CoA carboxylase accompanied by inhibition of the 5'-AMP-activated protein kinase. J Biol Chem. 1992 Feb 15;267(5):2864–2867. [PubMed]
  • Davies SP, Carling D, Munday MR, Hardie DG. Diurnal rhythm of phosphorylation of rat liver acetyl-CoA carboxylase by the AMP-activated protein kinase, demonstrated using freeze-clamping. Effects of high fat diets. Eur J Biochem. 1992 Feb 1;203(3):615–623. [PubMed]
  • Iritani N. Nutritional and hormonal regulation of lipogenic-enzyme gene expression in rat liver. Eur J Biochem. 1992 Apr 15;205(2):433–442. [PubMed]

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

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

  • Compound
    Compound
    PubChem Compound links
  • MedGen
    MedGen
    Related information in MedGen
  • PubMed
    PubMed
    PubMed citations for these articles
  • Substance
    Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...