Abstract
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.
References
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 119:325–334
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 169:296–302
Else PL, Windmill DJ, Markus V (1996) Molecular activity of sodium pumps in endotherms and ectotherms. Am J Physiol 271:R1287–R1294
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 124:318–325
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 297–310
Hazel JR (1995) Thermal adaptation in biological membranes: is homeoviscous adaptation the explanation? Annu Rev Physiol 57:19–42
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 433:271–281
Hibbeln J (1998) Fish consumption and major depression. Lancet 351:1213
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 69:15–29
Horrobin DF (1998) The membrane phospholipid hypothesis as a biochemical basis for the neurodevelopmental concept of schizophrenia. Schizophr Res 30:193–208
Horrocks LA, Yeo YK (1999) Health benefits of docosahexaenoic acid (DHA). Pharmacol Res 40:211–225
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 124:298–309
Hulbert AJ, Else PL (1999) Membranes as possible pacemakers of metabolism. J Theor Biol 199:257–274
Hulbert AJ, Else PL (2000) Mechanisms underlying the cost of living in animals. Annu Rev Physiol 62:207–235
Hulbert AJ, Faulks S, Buttemer WA, Else PL (2002a) Acyl composition of muscle membranes varies with body size in birds. J Exp Biol 205:3561–3569
Hulbert AJ, Rana T, Couture P (2002b) The acyl composition of mammalian phospholipids: an allometric analysis. Comp Biochem Physiol B 132:515–527
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 240–241
Raynard RS, Cossins AR (1991) Homeoviscous adaptation and thermal compensation of sodium pump of trout erythrocytes. Am J Physiol 260:R916–R924
Sprecher H (2000) Metabolism of highly unsaturated n-3 and n-6 fatty acids. Biochim Biophys Acta 1486:219–231
Stillwell W, Jenski LJ, Crump FT, Ehringer W (1997) Effect of docosahexaenoic acid on mouse mitochondrial membrane properties. Lipids 32:497–506
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 237:885–888
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 40:280–289
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 52:529–531
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 37:1044–1050
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 204:4271–4280
Yao JK, Leonard S, Reddy RD (2000) Membrane phospholipid abnormalities in postmortem brains from schizophrenic patients. Schizophr Res 42:7–17
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 1236:266–272
Acknowledgements
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.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Turner, N., Else, P.L. & Hulbert, A.J. Docosahexaenoic acid (DHA) content of membranes determines molecular activity of the sodium pump: implications for disease states and metabolism. Naturwissenschaften 90, 521–523 (2003). https://doi.org/10.1007/s00114-003-0470-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00114-003-0470-z