Carbon recycling into de novo lipogenesis is a major pathway in neonatal metabolism of linoleate and alpha-linolenate

Recent reports indicate that recycling of the beta-oxidized carbon skeleton of linoleate and a-linolenate into newly synthesized cholesterol and fatty acids in the brain is quantitatively significant in both suckling rats and pre- and postnatally in rhesus monkeys. The recycling appears to occur via ketones which are not only readily produced from these 18 carbon polyunsat urates but are also the main lipogenic precursors for the developing mammal ian brain. Since the neonatal rat brain appears not to acquire cholesterol or long chain saturated or monounsaturated fatty acids from the circulation , ketones and ketogenic precursors seem to be crucial for normal brain synt hesis of these lipids. Cholesterol is plentiful in brain membranes and it h as also been discovered to be the essential lipid adduct of the 'hedgehog' family of proteins, the appropriate expression of which determines normal e mbryonic tissue patterning and neurological development. Insufficient chole sterol or inappropriate expression of 'sonic hedgehog' has major adverse ne urodevelopmental consequences typified in humans by Smith-Lemli-Optiz syndr ome. Hence, we propose that the importance of a-linolenate and linoleate fo r normal neural development arises not only from being precursors to longer chain polyunsaturates incorporated into neuronal membranes but, perhaps eq ually importantly, by being ketogenic precursors needed for in situ brain l ipid synthesis.