Entry of [(1,2-C-13(2))acetyl]-L-carnitine in liver tricarboxylic acid cycle and lipogenesis - A study by C-13 NMR spectroscopy in conscious, freely moving rats

The biochemical pathways involved in acetyl-L-carnitine utilization were in vestigated in conscious, freely moving rats by C-13 NMR spectroscopy. Follo wing 4-h [(1,2-C-13(2))acetyl]-L-carnitine infusion in fasted animals, the free carnitine levels in serum were increased, and an efflux of unlabelled acety-L-carnitine from tissues was observed. [(1,2-C-13(2))Acetyl]-L-carnit ine was found to enter biosynthetic pathways in liver, and the acetyl moiet y was incorporated into both cholesterol and 3-hydroxybutyrate carbon skele ton. In accord with the entry of [(1,2-C-13(2))acetyl]-L-carnitine in the m itochondrial acetylCoA pool associated with tricarboxylic acid cycle, the C -13 label was also found in liver glutamate, glutamine, and glutathione. Th e analysis of the C-13-labelling pattern in 3-hydroxybutyrate and cholester ol carbon skeleton provided evidence that the acetyl-L-carnitine-derived ac etylCoA pool used for ketone bodies synthesis in mitochondria was homogeneo us, whereas cholesterol was synthesized from two different acetylCoA pools located in the extra- and intramitochondrial compartment, respectively. Fur thermore, cholesterol molecules were shown to be preferentially synthesized by the metabolic route involving the direct channelling of CoA-activated m itochondria-derived ketone bodies into 3-hydroxy-3-methylglutarylCoA pathwa y, prior to equilibration of their acyl groups with extramitochondrial acet ylCoA pool via acetoacetylCoA thiolase.