1. The incorporation of [1-14C] acetate in vivo into the three major classes of fatty acid (i.e. fatty acids from phospholipids, neutral glyceride fatty acids and unesterified fatty acids) in rat cerebral cortex has been measured. These measurements have shown that endogenous unesterified fatty acids turn over rapidly in vivo, with a half-life of approximately five minutes. Furthermore, under normal non-stimulated conditions unesterified fatty acids are rapidly incorporated into phospholipids and neutral glycerides. 2. A washing procedure has been developed which effectively reduces the contamination of the fatty acid extracts by unmetabolized acetate present in the excised tissue. 3. It has been shown that radioactively labelled acetate is rapidly incorporated into the unesterified fatty acids associated with subcellular fractions of rat cerebral cortex in vivo. 4. The level of long-chain fatty acyl-CoA esters in rat brain has been determined. The incorporation of [1-14C] acetate in vivo into the long-chain fatty acyl-CoA esters of rat brain has also been measured. These measurements have shown that the thioesters turn over rapidly in vivo with a half-life of approximately thirty seconds. 5. The subcellular localization of the enzyme long-chain fatty acyl-CoA hydrolase has been investigated. The results have shown that the enzyme is almost entirely soluble in nature and that it is not localized in any particular subcellular fraction from rat cerebral cortex. 6. A possible control mechanism for the enzyme in vivo has also been investigated. The enzyme is inhibited by Ca2+ and Mg2+ and by bovine serum albumin, but is not affected by neurotransmitters and free fatty acids. 7. The role of the enzyme long-chain fatty acyl-CoA hydrolase in brain has been examined and it is suggested that the enzyme may be involved in the maintenance of the unesterified fatty acid pool in brain.
|Date of Award||1976|