ENERGY-REQUIREMENTS FOR 2 ASPECTS OF PHOSPHOLIPID-METABOLISM IN MAMMALIAN BRAIN

Previous estimates have placed the energy requirements of total phosph olipid metabolism in mammalian brain at 2% or less of total ATP consum ption. 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, whic h takes into account dilution of the precursor acyl-CoA pool by recycl ing of fatty acids, we reported that half-lives of fatty acids in phos pholipids are some 100 times shorter (min-h) than previously thought. Based on these new estimates of short half-lives, palmitic acid and ar achidonic 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 re acylation of fatty acids into lysophospholipids are 5% of net brain AT P consumption. We also calculated ATP requirements for maintaining asy mmetry of the aminophospholipids, phosphatidylserine and phosphatidyle thanolamine across brain membrane bilayers. This asymmetry is maintain ed by a translocase at a stoichiometry of 1 mol of ATP per mol of phos pholipid transferred in either direction across the membrane. The ener gy cost of maintaining membrane bilayer asymmetry of aminophospholipid s at steady-state was calculated to be 8% of total ATP consumed. Taken together, deacylation-reacylation and maintenance of membrane asymmet ry of phosphatidylserine and phosphatidylethanolamine require about 13 % of ATP consumed by brain as a whole. This is a lower limit for energ y consumption by processes involving phospholipids, as other processes , including phosphorylation of polyphosphoinositides and de novo phosp holipid biosynthesis, were not considered.