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.
Purdon
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Laboratory of Neurosciences, National Institutes on Aging, National Institutes of Health, Bethesda, MD, 20892-1582, USA.
Rapoport
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SI
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