In vivo fatty acid incorporation into brain phospholipids in relation to signal transduction and membrane remodeling.

A method and model are described to quantify in vivo turnover rates and half-lives of fatty acids within brain phospholipids. These "kinetic" parameters can be calculated by operational equations from measured rates of incorporation of intravenously injected fatty acid radiotracers into brain phospholipids. To do this, it is necessary to determine a "dilution factor" lambda, which estimates the contribution to the brain precursor acyl-CoA pool of fatty acids released from phospholipids through the action of PLA1 or PLA2. Some calculated fatty acid half-lives are minutes to hours, consistent with active participation of phospholipids in brain function and structure. The fatty acid method can be used to identify enzyme targets of drugs acting on phospholipid metabolism. For example, a reduced brain turnover of arachidonate by chronic lithium, demonstrated in rats by the fatty acid method, suggests that this agent, which is used to treat bipolar disorder, has for its target an arachidonate-specific PLA2. In another context, when combined with in vivo imaging by quantitative autoradiography in rodents or positron emission tomography in macaques or humans, the fatty acid method can localize and quantify normal and modified PLA2-mediated signal transduction in brain.