Transmembrane transport of fatty acids in the heart

  • Wolfgang Stremmel
Part of the Developments in Molecular and Cellular Biochemistry book series (DMCB, volume 5)


Although fatty acid uptake by the myocardium is rapid and efficient, the mechanism of their transmembrane transport has been unclear. Fatty acids are presented to the plasma membrane of cardiomyocytes as albumin complexes within the plasma. Since albumin is not taken up by the cells, it was postulated that specific high affinity binding sites at the sarcolemma may mediate the dissociation of fatty acids from the albumin molecules, before they are transported into the cells. In studies with a representative long-chain fatty acid, oleate, it was in fact shown that fatty acids bind with high affinity to isolated plasma membranes of rat heart myocytes revealing a KD of 42 nM. Moreover, a specific membrane fatty acid-binding protein (MFABP) was isolated from these membranes. It had a molecular weight of 40kD, an isoelectric point of 9.0, and lacked carbohydrate or lipid components. Binding to a specific membrane protein might represent the first step of a carrier mediated uptake process. Therefore, the uptake kinetics of oleate by isolated rat heart myocytes was determined under conditions where only cellular influx and not metabolism occurred. Uptake revealed saturation kinetics and was temperature dependent which were considered as specific criteria for a facilitated transport mechanism. For evaluation whether uptake is mediated by MFABP, the effect of a monospecific antibody to this protein on cellular influx of oleate was examined. Inhibition of uptake of fatty acids but not of glucose by the antibody to MFABP indicated the physiologic significance of this protein as transmembrane carrier in the cellular uptake process of fatty acids. Such a transporter might represent an important site for the metabolic regulation of fatty acid influx into the myocardium.

Key words

fatty acid metabolism cardiomyocytes carrier mediated uptake 


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  1. 1.
    Wisneski JA, Gertz EW, Neese RA, Mayr M: Myocardial metabolism of free fatty acids: Studies with 14C-labeled substrates in humans. J Clin Invest 79: 359–366, 1987PubMedCrossRefGoogle Scholar
  2. 2.
    Vyska K, Machulla HJ, Stremmel W, Faßbender D, Knapp WH, Notohamiprodjo G, Gleichmann U, Meyer H, Knust EJ, Körfer R: Regional myocardial free fatty acid extraction in normal and ischemic myocardium. Circulation 78: 1218–1233, 1988PubMedCrossRefGoogle Scholar
  3. 3.
    Weisiger RA, Gollan JD, Ockner RK: The role of albumin in hepatic uptake processes. In H Popper and F. Schaffner (eds) Progress in Liver Disease, Vol VII, Grune & Stratton, New York, 1982, pp 71–85Google Scholar
  4. 4.
    Weisiger RA, Gollan J, Ockner R: Receptor for albumin on the liver cell surface may mediate uptake of fatty acids and other albumin-bound substances. Science 211: 1048–1051,1981PubMedCrossRefGoogle Scholar
  5. 5.
    Weisiger RA, Ma WL: Uptake of oleate from albumin solutions by rat liver: Failure to detect catalysis of the dissociation of oleate from albumin by an albumin receptor. J Clin Invest 79: 1070–1077, 1987PubMedCrossRefGoogle Scholar
  6. 6.
    Berk PD, Potter BJ, Stremmel W: Role of plasma membrane ligand-binding proteins in the hepatocellular uptake of albumin-bound organic anions. Hepatology 7: 165–176, 1987PubMedCrossRefGoogle Scholar
  7. 7.
    Nunes RM, Kiang CL, Berk PD: ‘Albumin receptor’ uptake kinetics do not require an intact hepatic lobular architecture, and are not albumin specific. Hepatology 5: 353, 1985 (Abstr.)Google Scholar
  8. 8.
    Inoue M: Metabolism and transport of amphipathic molecules in analbuminemic rats and human subjects. Hepatology 5: 892–898, 1985PubMedCrossRefGoogle Scholar
  9. 9.
    Stremmel W, Potter BJ, Berk PD: Studies of albumin binding to rat liver plasma membranes: implications for the albumin receptor hypothesis. Biochim Biophys Acta 756: 20–27, 1983PubMedGoogle Scholar
  10. 10.
    Schnitzler JA, Carley WW, Palade GE: Specific albumin binding to microvascular endothelium in culture. Am J Physiol H425–H437, 1988Google Scholar
  11. 11.
    Sage H, Johnson C, Bornstein P: Characterization of a novel serum albumin-binding glycoprotein secreted by endothelial cells in culture. J Biol Chem 259: 3993–4007,1984PubMedGoogle Scholar
  12. 12.
    Stremmel W: Fatty acid uptake by isolated rat heart myocytes represents a carrier mediated transport process. J Clin Invest 81: 844–852, 1988PubMedCrossRefGoogle Scholar
  13. 13.
    Ockner RK, Manning JA, Poppenhausen RB, Ho WKL: A binding protein for fatty acids in cytosol of intestinal mucosa, liver, myocardium, and other tissues. Science (Wash. DC) 177: 56–58, 1972CrossRefGoogle Scholar
  14. 14.
    Sorrentino D, Robinson R, Kiang CL, Stumpf D, Potter BJ, Berk PD: Mechanism of oleate uptake by isolated cardiac myocytes. Clin Research 35: 575A, 1987 (Abstr.)Google Scholar
  15. 15.
    Stremmel W, Strohmeyer G, Berk PD: Hepatocellular uptake of oleate is energy dependent, sodium linked, and inhibited by an antibody to a hepatocyte plasma membrane fatty acid binding protein. Proc Natl Acad Sci USA 83: 3584–3588, 1986PubMedCrossRefGoogle Scholar
  16. 16.
    Stremmel W: Uptake of fatty acids by jejunal mucosal cells is mediated by a fatty acid binding membrane protein. J Clin Invest: 82: 2001–2010, 1988PubMedCrossRefGoogle Scholar
  17. 17.
    Schwieterman W, Sorrentino D, Potter BJ, Rand J, Kiang CL, Stump D, Berk PD: Uptake of oleate by isolated rat adipocytes is mediated by a 40 kDa plasma membrane fatty acid binding protein closely related to that in liver and gut. Proc Natl Acid Sci USA 85: 359–363, 1988CrossRefGoogle Scholar
  18. 18.
    Stremmel W: Translocation of fatty acids across the basolateral rat liver plasma membrane is driven by an active potential-sensitive sodium-dependent transport system. J Biol Chem 262: 6284–6289, 1987PubMedGoogle Scholar
  19. 19.
    Weisiger RA, Fitz JG, Scharschmidt BF: Hepatic oleate uptake: Electrochemical driving forces in the intact rat liver. J Clin Invest 1988 (in press)Google Scholar

Copyright information

© Kluwer Academic Publishers 1989

Authors and Affiliations

  • Wolfgang Stremmel
    • 1
  1. 1.Department of Internal MedicineUniversity Clinics of DüsseldorfGermany

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