Energy requirements for two aspects of phospholipid metabolism in mammalian brain

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.

Imaging Brain Phospholipase A2-Mediated Signal Transduction in Response to Acute Fluoxetine Administration in Unanesthetized Rats

“…A similar discrepancy between increased radiolabeled arachidonate incorporation but decreased or no change in rCMR glc follows DOI or methiothepin administration to unanesthetized rats (Freo et al, 1991;Qu et al, 2001b;Ricchieri et al, 1987). These discrepancs likely arise because [ 3 H]arachidonate incorporation localizes the postsynaptic PLA 2 -mediated release of arachidonic acid at the serotonergic neuron, whereas rCMR glc represents ATP consumption by the downstream firing of presynaptic axon terminals of that neuron (Ashby et al, 1990;Purdon and Rapoport, 1998;Qu et al, 2003;Sokoloff, 1999).…”

Imaging incorporation of circulating docosahexaenoic acid into the human brain using positron emission tomography

“…K* for DHA is thought to reflect the rate of DHA consumption by brain, in relation to the role of DHA in signaling and to its metabolism to docosanoids and other products, including reactive oxygen species (21,22,(61)(62)(63). rCBF, which is coupled to brain glucose consumption (64), is thought to reflect any of a number of energy-demanding metabolic processes, including synaptic activation and reincorporation of unesterified DHA into membrane phospholipid (65,66). K* for fatty acids has been shown to be independent of changes in rCBF during functional activation or hypercapnia in rats and in patients with Alzheimerʼs disease (16,22,67).…”

Mitochondrial dysfunction in bipolar disorder: evidence from magnetic resonance spectroscopy research

“…In a normal brain cell, the synthesis and maintenance of the cell membrane require between 10 and 15% of net brain ATP production (Figure 3). 79 If less energy is produced in the cell overall, it is likely that aspects of phospholipid metabolism, including de novo phospholipid biosynthesis, would also be impaired. Several MRS studies have indicated that phospholipid metabolism is indeed abnormal in bipolar patients, as evidenced by alterations in levels of Cho, mI, inositol monophosphates, and PMEs (Tables 6-10).…”