Kinetic methods in unanesthetized rodents have shown that turnover rates of
arachidonic acid (AA) and
docosahexaenoic acid (DHA) in brain membrane
phospholipids are rapid and energy consuming and that
phospholipase A(2) (PLA(2)) and
acyl-CoA synthetase enzymes that regulate turnover are specific for one or the other PUFA. Thus, AA turnover in brain
phospholipids was reduced, and AA-selective cytosolic cPLA(2) or
acyl-CoA synthetase, as well as
cyclooxygenase (COX)-2, were downregulated in brains of rats given drugs effective against
bipolar disorder, whereas DHA turnover and expression of DHA-selective
calcium-independent
iPLA(2) were unchanged. Additionally, the brain AA and DHA cascades can be altered reciprocally by dietary or genetic conditions. Thus, following 15 wk of dietary (n-3) PUFA deprivation, DHA loss from rat brain was slowed because of reduced
iPLA(2) and COX-1 expression, whereas AA-selective cPLA(2),
sPLA(2), and COX-2 were upregulated, as were AA and
docosapentaenoic acid concentrations. Measured rates of AA and DHA incorporation into brain represent their respective rates of metabolic consumption, because these PUFA are not synthesized de novo or converted significantly from their precursors in brain. In healthy human volunteers, positron emission tomography (PET) was used to show that the brain consumes AA and DHA at respective rates of 17.8 and 4.6 mg/d, whereas in patients with
Alzheimer disease, AA consumption is elevated. In the future, PET could be used to relate human brain rates of AA and DHA consumption to liver PUFA metabolism and dietary PUFA intake.