Energy requirements for two aspects of phospholipid metabolism in mammalian brain.
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.
Laboratory of Neurosciences, National Institutes on Aging, National Institutes of Health, Bethesda, MD, 20892-1582, USA.
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Purdon
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Rapoport
D000214:Acyl Coenzyme A / Q000378:metabolism; D000215:Acylation; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001692:Biological Transport; D001921:Brain / Q000378:metabolism*; D004734:Energy Metabolism; D005227:Fatty Acids / Q000378:metabolism; D008246:Lysophospholipids / Q000378:metabolism; D008322:Mammals / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism; D008954:Models, Biological; D010743:Phospholipids / Q000378:metabolism*
D000214:Acyl Coenzyme A; D005227:Fatty Acids; D008246:Lysophospholipids; D008562:Membrane Glycoproteins; D010743:Phospholipids; D000255:Adenosine Triphosphate