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

Abstract: The biochemical pathways involved in acetyl-L-carnitine utilization were investigated in conscious, freely moving rats by C-13 NMR spectroscopy. Following 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-carnitine was found to enter biosynthetic pathways in liver, and the acetyl moiety was incorporated into both cholesterol and 3-hydroxybutyrate carbon skeleton. In accord with the entry of [(1,2-C-13(2))acetyl]-L-carnitine in the mitochondrial acetylCoA pool associated with tricarboxylic acid cycle, the C-13 label was also found in liver glutamate, glutamine, and glutathione. The analysis of the C-13-labelling pattern in 3-hydroxybutyrate and cholesterol carbon skeleton provided evidence that the acetyl-L-carnitine-derived acetylCoA pool used for ketone bodies synthesis in mitochondria was homogeneous, whereas cholesterol was synthesized from two different acetylCoA pools located in the extra- and intramitochondrial compartment, respectively. Furthermore, cholesterol molecules were shown to be preferentially synthesized by the metabolic route involving the direct channelling of CoA-activated mitochondria-derived ketone bodies into 3-hydroxy-3-methylglutarylCoA pathway, prior to equilibration of their acyl groups with extramitochondrial acetylCoA pool via acetoacetylCoA thiolase.