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Entry of [(1,2-13C2)acetyl]-L-carnitine in Liver Tricarboxylic Acid Cycle and Lipogenesis: A Study by 13C NMR Spectroscopy in Conscious, Freely Moving Rats

T Aureli, C Puccetti, M E Di Cocco, A Arduini, R Ricciolini, M Scalibastri, C Manetti, F Conti

Eur J Biochem. 1999 Jul;263(1):287-93.

PMID: 10429215

Abstract:

The biochemical pathways involved in acetyl-L-carnitine utilization were investigated in conscious, freely moving rats by 13C NMR spectroscopy. Following 4-h [(1,2-13C2)acetyl]-L-carnitine infusion in fasted animals, the free carnitine levels in serum were increased, and an efflux of unlabelled acetyl-L-carnitine from tissues was observed. [(1,2-13C2)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 [(1,2-13C2)acetyl]-L-carnitine in the mitochondrial acetylCoA pool associated with tricarboxylic acid cycle, the 13C label was also found in liver glutamate, glutamine, and glutathione. The analysis of the 13C-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.

Chemicals Related in the Paper:

Catalog Number Product Name Structure CAS Number Price
AP754966217 Pyruvic-1,2-13C2 acid Pyruvic-1,2-13C2 acid 754966-21-7 Price
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