Identifying the specific enzyme isoforms that regulate brain fatty acid metabolism

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Fatty acids make up a large portion of the brain cell membranes. When released from these membranes (by an enzyme called phospholipase A2) the fatty acids can then help brain cells communicate with each other. By changing the dietary intake of fatty acids we can change the fatty acid composition of brain cell membranes. This in turn changes the amount and types of fatty acids that are released from the membranes by phospholipase A2 and thus changes how brain cells communicate with each other. With the advent of molecular biology we now know there are multiple forms (called isoforms) of phospholipase A2 within the brain. How these phospholipase A2 isoforms differ in their ability to release specific fatty acids from the membrane is not known. The overall goal of my research is to identify if the different phospholipase A2 isoforms are selective in the type of fatty acids they release. By doing so, I am also testing if we can modify the amount of a specific phospholipase A2 isoform by providing more or less of the type of fatty acids it is selective for in the diet. Scientists have now reported many different conditions where specific phospholipase A2 isoforms are overactive, including Alzheimer's disease and Bipolar disorder. If we better understand what fatty acids these phospholipases are releasing, we might have a better insight into whether or not diets high or low in certain fatty acids could be beneficial in treating these conditions.