The autocoids derived from different unsaturated fatty acids mediate physiological processes in diverse ways. The types and amounts of autocoids produced in any cell depend on what unsaturated fatty acids are found in individual phospholipids for agonist induced release by specific lipases for subsequent metabolism to leukotrienes and prostaglandins. Phospholipid unsaturated fatty acid composition differs between prostaglandin producing cells.
Aim one of this study involves carefully controlled rat feeding studies using deuterated unsaturated acids, to define what differences exist in their time dependent incorporation into individual phospholipids in a number of prostaglandin producing tissues. These feeding studies will also define whether unsaturated fatty acid and phospholipid biosynthesis studies will also define whether unsaturated fatty acid and phospholipid biosynthesis are coupled metabolic processes and what differences exist in the tissues which make their own polyunsaturated acids versus leucocytes and platelets which largely depend on plasma for acids for phospholipid synthesis. Competitive feeding studies with deuterated (n-3) and (n-6) acids will compare how these acids are metabolized and incorporated into specific phospholipids and what differences exist between lipids within a tissue and between tissues. In the second phase of these studies rat hepatocytes will be incubated with various radioactive (n-6) and (n-3) polyunsaturated fatty acids to define 1. Whether polyunsaturated fatty acid biosynthesis and phospholipid biosynthesis are coupled metabolic processes. 2. Whether exogenous arachidonic acid inhibits metabolism of linoleate to archidonate and its subsequent acylation into individual phospholipids. 3. What interactions exist between (n-3) and (n-6) acids to regulate individual phospholipid fatty acid composition and thus physiological function. The third phase of these studies will define what regulates the synthesis of 22-carbon (n-3) and (n-6) fatty acids with particular emphasis on elucidating the pathway by which a double bond is introduced at position-4 of unsaturated acids. The overall goal of these studies is to determine how dietary fat change regulates the unsaturated fatty acid composition of individual phospholipids in prostaglandin producing tissues.
