Metabolism of AC-1202 (MCTs) versus LCTs. MCTs are emulsifed in the gut lumen, where gastrointestinal lipases hydrolyze them to MCFAs. MCFAs are absorbed directly into the portal vein and, unlike LCT, are not packaged into lipoproteins. In the liver, MCFAs are quickly oxidized, whereas the fate of LCFAs is dependent on the metabolic state of the organism. LCFAs are transported to the mitochondria for oxidation using CPT1. When conditions favor fat storage, malonyl-CoA is produced as an intermediate in lipogenesis. Malonyl-CoA inhibits CPT1, and prevents oxidation of LCFAs in the mitochondria. MCFAs enter the mitochondria without the use of CPT1 and are not subject to the regulations that control the oxidation of LCFAs. Because MCFAs enter the liver rapidly and are quickly oxidized, a large oral dose of MCT will result in sustained hyperketonemia. CoA, coenzyme A; CPT1, carnitine palmitoyltransferase I; LCDG, diglyceride; LCFA, long-chain fatty acid; LCMG, long-chain monoglyceride; LCT, long-chain triglyceride; MCFA, medium-chain fatty acid; MCT, medium-chain triglyceride; TG, triglyceride.
Costantini et al. BMC Neuroscience 2008 9(Suppl 2):S16 doi:10.1186/1471-2202-9-S2-S16