, Volume 90, Issue 11, pp 521–523 | Cite as

Docosahexaenoic acid (DHA) content of membranes determines molecular activity of the sodium pump: implications for disease states and metabolism

Short Communication


The omega-3 polyunsaturate, docosahexaenoic acid (DHA), plays a number of biologically important roles, particularly in the nervous system, where it is found in very high concentrations in cell membranes. In infants DHA is required for the growth and functional development of the brain, with a deficiency resulting in a variety of learning and cognitive disorders. During adulthood DHA maintains normal brain function and recent evidence suggests that reduced DHA intake in adults is linked with a number of neurological disorders including schizophrenia and depression. Here we report a high positive correlation between the molecular activity (ATP min−1) of individual Na+K+ATPase units and the content of DHA in the surrounding membrane bilayer. This represents a fundamental relationship underlying metabolic activity, but may also represent a link between reduced levels of DHA and neurological dysfunction, as up to 60% of energy consumption in the brain is linked to the Na+K+ATPase enzyme.



We thank Parisa Abolhasan for technical assistance. This work was supported by a grant from the Australian Research Council. All experimental procedures were performed in conformity with the National Health and Medical Research Council Guidelines for animal research in Australia and were approved by the Animal Experimentation Ethics committee of the University of Wollongong.


  1. Brookes PS, Buckingham JA, Tenreiro AM, Hulbert AJ, Brand MD (1998) The proton permeability of the inner membrane of liver mitochondria from ectothermic and endothermic vertebrates and from obese rats: correlations with standard metabolic rate and phospholipid fatty acid composition. Comp Biochem Physiol B 119:325–334PubMedGoogle Scholar
  2. Else PL, Wu BJ (1999) What role for membranes in determining the higher sodium pump molecular activity of mammals compared to ectotherms? J Comp Physiol B 169:296–302CrossRefPubMedGoogle Scholar
  3. Else PL, Windmill DJ, Markus V (1996) Molecular activity of sodium pumps in endotherms and ectotherms. Am J Physiol 271:R1287–R1294PubMedGoogle Scholar
  4. Feller SE, Gawrisch K, MacKerell AD Jr (2002) Polyunsaturated fatty acids in lipid bilayers: intrinsic and environmental contributions to their unique physical properties. J Am Chem Soc 124:318–325CrossRefPubMedGoogle Scholar
  5. Gudbjarnason S, Doell B, Oskardottir G, Hallgrimsson J (1978) Modification of cardiac phospholipids and catecholamine stress tolerance. In: Duve C de, Hayaishi O (eds) Tocopherol, oxygen and biomembranes. Elsevier, Amsterdam, pp 297–310Google Scholar
  6. Hazel JR (1995) Thermal adaptation in biological membranes: is homeoviscous adaptation the explanation? Annu Rev Physiol 57:19–42PubMedGoogle Scholar
  7. Hendriks TH, Klompmakers AA, Daemen FJM, Bonting SL (1976) Biochemical aspects of the visual process. XXXII. Movement of sodium ions through bilayers composed of retinal and rod outer segment lipids. Biochim Biophys Acta 433:271–281CrossRefGoogle Scholar
  8. Hibbeln J (1998) Fish consumption and major depression. Lancet 351:1213Google Scholar
  9. Hibbeln J (2002) Seafood consumption, the DHA content of mothers’ milk and prevalence rates of postpartum depression: a cross-national, ecological analysis. J Affect Disord 69:15–29CrossRefPubMedGoogle Scholar
  10. Horrobin DF (1998) The membrane phospholipid hypothesis as a biochemical basis for the neurodevelopmental concept of schizophrenia. Schizophr Res 30:193–208PubMedGoogle Scholar
  11. Horrocks LA, Yeo YK (1999) Health benefits of docosahexaenoic acid (DHA). Pharmacol Res 40:211–225CrossRefPubMedGoogle Scholar
  12. Huber T, Rajamoorthi K, Kurze VF, Beyer K, Brown MF (2002) Structure of docosahexaenoic acid-containing phospholipid bilayers as studied by 2H NMR and molecular dynamics simulations. J Am Chem Soc 124:298–309CrossRefPubMedGoogle Scholar
  13. Hulbert AJ, Else PL (1999) Membranes as possible pacemakers of metabolism. J Theor Biol 199:257–274PubMedGoogle Scholar
  14. Hulbert AJ, Else PL (2000) Mechanisms underlying the cost of living in animals. Annu Rev Physiol 62:207–235CrossRefPubMedGoogle Scholar
  15. Hulbert AJ, Faulks S, Buttemer WA, Else PL (2002a) Acyl composition of muscle membranes varies with body size in birds. J Exp Biol 205:3561–3569PubMedGoogle Scholar
  16. Hulbert AJ, Rana T, Couture P (2002b) The acyl composition of mammalian phospholipids: an allometric analysis. Comp Biochem Physiol B 132:515–527CrossRefPubMedGoogle Scholar
  17. Mills GL, Lane PA, Weech PK (1984) A guidebook to lipoprotein technique. In: Knippenberg PH van (ed) Laboratory techniques in biochemistry and molecular biology, vol 14. Elsevier Science, New York, pp 240–241Google Scholar
  18. Raynard RS, Cossins AR (1991) Homeoviscous adaptation and thermal compensation of sodium pump of trout erythrocytes. Am J Physiol 260:R916–R924PubMedGoogle Scholar
  19. Sprecher H (2000) Metabolism of highly unsaturated n-3 and n-6 fatty acids. Biochim Biophys Acta 1486:219–231CrossRefPubMedGoogle Scholar
  20. Stillwell W, Jenski LJ, Crump FT, Ehringer W (1997) Effect of docosahexaenoic acid on mouse mitochondrial membrane properties. Lipids 32:497–506PubMedGoogle Scholar
  21. Storlien LH, Kraegen EW, Chisholm DJ, Ford GL, Bruce DG, Pascoe WS (1987) Fish oil prevents insulin resistance induced by high-fat feeding in rats. Science 237:885–888PubMedGoogle Scholar
  22. Storlien LH, Jenkins AB, Chisholm DJ, Pascoe WS, Khouri S, Kraegen EW (1991) Influence of dietary fat composition on development of insulin resistance in rats: Relationship to muscle triglyceride and omega-3 fatty acids in muscle phospholipid. Diabetes 40:280–289PubMedGoogle Scholar
  23. Tanskanen A, Hibbeln JR, Tuomilehto J, Uutela A, Haukkala A, Viinamäki H, Lehtonen J, Vartainen E (2001) Fish consumption and depressive symptoms in the general population in Finland. Psyc Serv 52:529–531CrossRefGoogle Scholar
  24. Vessby B, Tengblad S, Lithel H (1994) Insulin sensitivity is related to the fatty acid composition of serum lipids and skeletal muscle phospholipids in 70-year-old men. Diabetologia 37:1044–1050CrossRefPubMedGoogle Scholar
  25. Wu BJ, Else PL, Storlien LH, Hulbert AJ (2001) Molecular Activity of Na+/K+-ATPase from different sources is related to the packing of membrane lipids. J Exp Biol 204:4271–4280PubMedGoogle Scholar
  26. Yao JK, Leonard S, Reddy RD (2000) Membrane phospholipid abnormalities in postmortem brains from schizophrenic patients. Schizophr Res 42:7–17CrossRefPubMedGoogle Scholar
  27. Zerouga M, Jenski LJ, Stillwell W (1995) Comparison of phosphatidylcholines containing one or two docosahexaenoic acyl chains on properties of phospholipid monolayers and bilayers. Biochim Biophys Acta 1236:266–272CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2003

Authors and Affiliations

  • Nigel Turner
    • 1
    • 2
  • Paul L. Else
    • 1
    • 2
  • A. J. Hulbert
    • 1
    • 3
  1. 1.Metabolic Research CentreUniversity of WollongongWollongongAustralia
  2. 2.Department of Biomedical SciencesUniversity of WollongongWollongongAustralia
  3. 3.Department of Biological SciencesUniversity of WollongongWollongongAustralia

Personalised recommendations