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. 1998 Oct 15;335(Pt 2):313–318. doi: 10.1042/bj3350313

Energy requirements for two aspects of phospholipid metabolism in mammalian brain.

A D Purdon 1, S I Rapoport 1
PMCID: PMC1219784  PMID: 9761729

Abstract

Previous estimates have placed the energy requirements of total phospholipid metabolism in mammalian brain at 2% or less of total ATP consumption. This low estimate was consistent with the very long half-lives (up to days) reported for fatty acids esterified within phospholipids. However, using an approach featuring analysis of brain acyl-CoA, which takes into account dilution of the precursor acyl-CoA pool by recycling of fatty acids, we reported that half-lives of fatty acids in phospholipids are some 100 times shorter (min-h) than previously thought. Based on these new estimates of short half-lives, palmitic acid and arachidonic acid were used as prototype fatty acids to calculate energy consumption by fatty acid recycling at the sn-1 and sn-2 positions of brain phospholipids. We calculated that the energy requirements for reacylation of fatty acids into lysophospholipids are 5% of net brain ATP consumption. We also calculated ATP requirements for maintaining asymmetry of the aminophospholipids, phosphatidylserine and phosphatidylethanolamine across brain membrane bilayers. This asymmetry is maintained by a translocase at a stoichiometry of 1 mol of ATP per mol of phospholipid transferred in either direction across the membrane. The energy cost of maintaining membrane bilayer asymmetry of aminophospholipids at steady-state was calculated to be 8% of total ATP consumed. Taken together, deacylation-reacylation and maintenance of membrane asymmetry of phosphatidylserine and phosphatidylethanolamine require about 13% of ATP consumed by brain as a whole. This is a lower limit for energy consumption by processes involving phospholipids, as other processes, including phosphorylation of polyphosphoinositides and de novo phospholipid biosynthesis, were not considered.

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Selected References

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  1. Allan D. Mapping the lipid distribution in the membranes of BHK cells (mini-review). Mol Membr Biol. 1996 Apr-Jun;13(2):81–84. doi: 10.3109/09687689609160580. [DOI] [PubMed] [Google Scholar]
  2. Auland M. E., Roufogalis B. D., Devaux P. F., Zachowski A. Reconstitution of ATP-dependent aminophospholipid translocation in proteoliposomes. Proc Natl Acad Sci U S A. 1994 Nov 8;91(23):10938–10942. doi: 10.1073/pnas.91.23.10938. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Baker R. R., Chang H. Y. A comparison of lysophosphatidylcholine acyltransferase activities in neuronal nuclei and microsomes isolated from immature rabbit cerebral cortex. Biochim Biophys Acta. 1981 Nov 23;666(2):223–229. doi: 10.1016/0005-2760(81)90111-9. [DOI] [PubMed] [Google Scholar]
  4. Beleznay Z., Zachowski A., Devaux P. F., Navazo M. P., Ott P. ATP-dependent aminophospholipid translocation in erythrocyte vesicles: stoichiometry of transport. Biochemistry. 1993 Mar 30;32(12):3146–3152. doi: 10.1021/bi00063a029. [DOI] [PubMed] [Google Scholar]
  5. Bishop W. R., Bell R. M. Assembly of the endoplasmic reticulum phospholipid bilayer: the phosphatidylcholine transporter. Cell. 1985 Aug;42(1):51–60. doi: 10.1016/s0092-8674(85)80100-8. [DOI] [PubMed] [Google Scholar]
  6. Bitbol M., Devaux P. F. Measurement of outward translocation of phospholipids across human erythrocyte membrane. Proc Natl Acad Sci U S A. 1988 Sep;85(18):6783–6787. doi: 10.1073/pnas.85.18.6783. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Connor J., Pak C. H., Zwaal R. F., Schroit A. J. Bidirectional transbilayer movement of phospholipid analogs in human red blood cells. Evidence for an ATP-dependent and protein-mediated process. J Biol Chem. 1992 Sep 25;267(27):19412–19417. [PubMed] [Google Scholar]
  8. Cook H. W. In vitro formation of polyunsaturated fatty acids by desaturation in rat brain: some properties of the enzymes in developing brain and comparisons with liver. J Neurochem. 1978 Jun;30(6):1327–1334. doi: 10.1111/j.1471-4159.1978.tb10463.x. [DOI] [PubMed] [Google Scholar]
  9. Deka N., Sun G. Y., MacQuarrie R. Purification and properties of acyl-CoA:1-acyl-sn-glycero-3-phosphocholine-O-acyltransferase from bovine brain microsomes. Arch Biochem Biophys. 1986 May 1;246(2):554–563. doi: 10.1016/0003-9861(86)90310-3. [DOI] [PubMed] [Google Scholar]
  10. Diaz C., Schroit A. J. Role of translocases in the generation of phosphatidylserine asymmetry. J Membr Biol. 1996 May;151(1):1–9. doi: 10.1007/s002329900051. [DOI] [PubMed] [Google Scholar]
  11. Ford D. A., Hale C. C. Plasmalogen and anionic phospholipid dependence of the cardiac sarcolemmal sodium-calcium exchanger. FEBS Lett. 1996 Sep 23;394(1):99–102. doi: 10.1016/0014-5793(96)00930-1. [DOI] [PubMed] [Google Scholar]
  12. Glaser P. E., Gross R. W. Rapid plasmenylethanolamine-selective fusion of membrane bilayers catalyzed by an isoform of glyceraldehyde-3-phosphate dehydrogenase: discrimination between glycolytic and fusogenic roles of individual isoforms. Biochemistry. 1995 Sep 26;34(38):12193–12203. doi: 10.1021/bi00038a013. [DOI] [PubMed] [Google Scholar]
  13. Grange E., Deutsch J., Smith Q. R., Chang M., Rapoport S. I., Purdon A. D. Specific activity of brain palmitoyl-CoA pool provides rates of incorporation of palmitate in brain phospholipids in awake rats. J Neurochem. 1995 Nov;65(5):2290–2298. doi: 10.1046/j.1471-4159.1995.65052290.x. [DOI] [PubMed] [Google Scholar]
  14. Heinrich R., Brumen M., Jaeger A., Müller P., Herrmann A. Modelling of phospholipid translocation in the erythrocyte membrane: a combined kinetic and thermodynamic approach. J Theor Biol. 1997 Apr 7;185(3):295–312. doi: 10.1006/jtbi.1996.0325. [DOI] [PubMed] [Google Scholar]
  15. Herrmann A., Zachowski A., Devaux P. F. Protein-mediated phospholipid translocation in the endoplasmic reticulum with a low lipid specificity. Biochemistry. 1990 Feb 27;29(8):2023–2027. doi: 10.1021/bi00460a010. [DOI] [PubMed] [Google Scholar]
  16. Hinkle P. C., Kumar M. A., Resetar A., Harris D. L. Mechanistic stoichiometry of mitochondrial oxidative phosphorylation. Biochemistry. 1991 Apr 9;30(14):3576–3582. doi: 10.1021/bi00228a031. [DOI] [PubMed] [Google Scholar]
  17. Masuzawa Y., Sugiura T., Ishima Y., Waku K. Turnover rates of the molecular species of ethanolamine plasmalogen of rat brain. J Neurochem. 1984 Apr;42(4):961–968. doi: 10.1111/j.1471-4159.1984.tb12697.x. [DOI] [PubMed] [Google Scholar]
  18. Masuzawa Y., Sugiura T., Sprecher H., Waku K. Selective acyl transfer in the reacylation of brain glycerophospholipids. Comparison of three acylation systems for 1-alk-1'-enylglycero-3-phosphoethanolamine, 1-acylglycero-3-phosphoethanolamine and 1-acylglycero-3-phosphocholine in rat brain microsomes. Biochim Biophys Acta. 1989 Sep 11;1005(1):1–12. doi: 10.1016/0005-2760(89)90024-6. [DOI] [PubMed] [Google Scholar]
  19. Moriyama Y., Nelson N., Maeda M., Futai M. Vanadate-sensitive ATPase from chromaffin granule membranes formed a phosphoenzyme intermediate and was activated by phosphatidylserine. Arch Biochem Biophys. 1991 Apr;286(1):252–256. doi: 10.1016/0003-9861(91)90037-j. [DOI] [PubMed] [Google Scholar]
  20. Pete M. J., Wu D. W., Exton J. H. Subcellular fractions of bovine brain degrade phosphatidylcholine by sequential deacylation of the sn-1 and sn-2 positions. Biochim Biophys Acta. 1996 Feb 16;1299(3):325–332. doi: 10.1016/0005-2760(95)00225-1. [DOI] [PubMed] [Google Scholar]
  21. Pumphrey A. M. Incorporation of [32P]orthophosphate into brain-slice phospholipids and their precursors. Effects of electrical stimulation. Biochem J. 1969 Mar;112(1):61–70. doi: 10.1042/bj1120061. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Rehncrona S., Westerberg E., Akesson B., Siesjö B. K. Brain cortical fatty acids and phospholipids during and following complete and severe incomplete ischemia. J Neurochem. 1982 Jan;38(1):84–93. doi: 10.1111/j.1471-4159.1982.tb10857.x. [DOI] [PubMed] [Google Scholar]
  23. Robinson P. J., Noronha J., DeGeorge J. J., Freed L. M., Nariai T., Rapoport S. I. A quantitative method for measuring regional in vivo fatty-acid incorporation into and turnover within brain phospholipids: review and critical analysis. Brain Res Brain Res Rev. 1992 Sep-Dec;17(3):187–214. doi: 10.1016/0165-0173(92)90016-f. [DOI] [PubMed] [Google Scholar]
  24. Roelofsen B., van Deenen L. L. Lipid requirement of membrane-bound ATPase. Studies on human erythrocyte ghosts. Eur J Biochem. 1973 Dec 3;40(1):245–257. doi: 10.1111/j.1432-1033.1973.tb03192.x. [DOI] [PubMed] [Google Scholar]
  25. Rolfe D. F., Brown G. C. Cellular energy utilization and molecular origin of standard metabolic rate in mammals. Physiol Rev. 1997 Jul;77(3):731–758. doi: 10.1152/physrev.1997.77.3.731. [DOI] [PubMed] [Google Scholar]
  26. Schmid P. C., Johnson S. B., Schmid H. H. Remodeling of rat hepatocyte phospholipids by selective acyl turnover. J Biol Chem. 1991 Jul 25;266(21):13690–13697. [PubMed] [Google Scholar]
  27. Seigneuret M., Devaux P. F. ATP-dependent asymmetric distribution of spin-labeled phospholipids in the erythrocyte membrane: relation to shape changes. Proc Natl Acad Sci U S A. 1984 Jun;81(12):3751–3755. doi: 10.1073/pnas.81.12.3751. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Sokoloff L., Reivich M., Kennedy C., Des Rosiers M. H., Patlak C. S., Pettigrew K. D., Sakurada O., Shinohara M. The [14C]deoxyglucose method for the measurement of local cerebral glucose utilization: theory, procedure, and normal values in the conscious and anesthetized albino rat. J Neurochem. 1977 May;28(5):897–916. doi: 10.1111/j.1471-4159.1977.tb10649.x. [DOI] [PubMed] [Google Scholar]
  29. Tang X., Halleck M. S., Schlegel R. A., Williamson P. A subfamily of P-type ATPases with aminophospholipid transporting activity. Science. 1996 Jun 7;272(5267):1495–1497. doi: 10.1126/science.272.5267.1495. [DOI] [PubMed] [Google Scholar]
  30. Verhoeven A. J., Tysnes O. B., Aarbakke G. M., Cook C. A., Holmsen H. Turnover of the phosphomonoester groups of polyphosphoinositol lipids in unstimulated human platelets. Eur J Biochem. 1987 Jul 1;166(1):3–9. doi: 10.1111/j.1432-1033.1987.tb13475.x. [DOI] [PubMed] [Google Scholar]
  31. WHITTAM R. The dependence of the respiration of brain cortex on active cation transport. Biochem J. 1962 Jan;82:205–212. doi: 10.1042/bj0820205. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Waku K. Origins and fates of fatty acyl-CoA esters. Biochim Biophys Acta. 1992 Mar 4;1124(2):101–111. doi: 10.1016/0005-2760(92)90085-a. [DOI] [PubMed] [Google Scholar]
  33. Washizaki K., Smith Q. R., Rapoport S. I., Purdon A. D. Brain arachidonic acid incorporation and precursor pool specific activity during intravenous infusion of unesterified [3H]arachidonate in the anesthetized rat. J Neurochem. 1994 Aug;63(2):727–736. doi: 10.1046/j.1471-4159.1994.63020727.x. [DOI] [PubMed] [Google Scholar]
  34. Wells M. A., Dittmer J. C. A comprehensive study of the postnatal changes in the concentration of the lipids of developing rat brain. Biochemistry. 1967 Oct;6(10):3169–3175. doi: 10.1021/bi00862a026. [DOI] [PubMed] [Google Scholar]
  35. Whittam R., Blond D. M. Respiratory control by an adenosine triphosphatase involved in active transport in brain cortex. Biochem J. 1964 Jul;92(1):147–158. doi: 10.1042/bj0920147. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Williamson P., Schlegel R. A. Back and forth: the regulation and function of transbilayer phospholipid movement in eukaryotic cells. Mol Membr Biol. 1994 Oct-Dec;11(4):199–216. doi: 10.3109/09687689409160430. [DOI] [PubMed] [Google Scholar]
  37. Xie X. S., Stone D. K., Racker E. Purification of a vanadate-sensitive ATPase from clathrin-coated vesicles of bovine brain. J Biol Chem. 1989 Jan 25;264(3):1710–1714. [PubMed] [Google Scholar]
  38. Zachowski A., Fellman P., Devaux P. F. Absence of transbilayer diffusion of spin-labeled sphingomyelin on human erythrocytes. Comparison with the diffusion of several spin-labeled glycerophospholipids. Biochim Biophys Acta. 1985 May 28;815(3):510–514. doi: 10.1016/0005-2736(85)90380-3. [DOI] [PubMed] [Google Scholar]
  39. Zachowski A., Gaudry-Talarmain Y. M. Phospholipid transverse diffusion in synaptosomes: evidence for the involvement of the aminophospholipid translocase. J Neurochem. 1990 Oct;55(4):1352–1356. doi: 10.1111/j.1471-4159.1990.tb03146.x. [DOI] [PubMed] [Google Scholar]
  40. Zachowski A. Phospholipids in animal eukaryotic membranes: transverse asymmetry and movement. Biochem J. 1993 Aug 15;294(Pt 1):1–14. doi: 10.1042/bj2940001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. de Kruijff B., van den Besselaar A. M., Cullis P. R., van den Bosch H., van Deenen L. L. Evidence for isotropic motion of phospholipids in liver microsomal membranes. A 31P NMR study. Biochim Biophys Acta. 1978 Dec 4;514(1):1–8. doi: 10.1016/0005-2736(78)90072-x. [DOI] [PubMed] [Google Scholar]

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