Open AccessEntry of [ (1,2‐ 13 C 2 )acetyl]‐ l ‐carnitine in liver tricarboxylic acid cycle and lipogenesis
Author(s) -
Aureli Tommaso,
Puccetti Caterina,
Di Cocco Maria Enrica,
Arduini Arduino,
Ricciolini Rita,
Scalibastri Maurizio,
Manetti Cesare,
Conti Filippo
Publication year - 1999
Publication title -
european journal of biochemistry
Language(s) - English
Resource type - Journals
eISSN - 1432-1033
pISSN - 0014-2956
DOI - 10.1046/j.1432-1327.1999.00524.x
Subject(s) - carnitine , citric acid cycle , biochemistry , acetyl coa , ketone bodies , chemistry , tricarboxylic acid , lipogenesis , acetylcarnitine , stereochemistry , metabolism , biology
The biochemical pathways involved in acetyl‐ l ‐carnitine utilization were investigated in conscious, freely moving rats by 13 C NMR spectroscopy. Following 4‐h [(1,2‐ 13 C 2 )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‐ 13 C 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‐ 13 C 2 )acetyl]‐ l ‐carnitine in the mitochondrial acetylCoA pool associated with tricarboxylic acid cycle, the 13 C label was also found in liver glutamate, glutamine, and glutathione. The analysis of the 13 C‐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.