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.
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.
Aureli
T
T
Department of Biochemistry, Sigma-Tau S.p.A. Research Labs, Pomezia, Italy.
Puccetti
C
C
Di Cocco
M E
ME
Arduini
A
A
Ricciolini
R
R
Scalibastri
M
M
Manetti
C
C
Conti
F
F
D000105:Acetyl Coenzyme A / Q000378:metabolism; D000108:Acetylcarnitine / Q000097:blood / Q000378:metabolism*; D000818:Animals; D002247:Carbon Isotopes; D002952:Citric Acid Cycle; D007657:Ketone Bodies / Q000378:metabolism; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008930:Mitochondria, Liver / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344
D002247:Carbon Isotopes; D007657:Ketone Bodies; D000108:Acetylcarnitine; D000105:Acetyl Coenzyme A