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This study was undertaken to explore the metabolic fate of acetyl‐l‐carnitine in rat brain. To measure the flux of carbon atoms into anabolic processes occurring at regional levels, we have injected [1‐14C]acetyl‐l‐carnitine into the lateral brain ventricle of conscious rats. After injection of [1‐14C]acetyl‐l‐carnitine, the majority of radioactivity was recovered as 14CO2 expired (60% of that injected). The percentage of radioactivity recovered in brain was 1.95, 1.60, 1.30, and 0.93% at 1, 3, 6, and 22 h, respectively. Radioactivity distribution in various lipid components indicated that the fatty acid moiety of phospholipid contained the majority of radioactivity. The radioactive profile of these fatty acids showed that the acetyl moiety of acetyl‐l‐carnitine was incorporated into saturated (60%), monounsaturated (15%), and polyunsaturated (25%) fatty acids [mainly present in 20:4 (5.2%) and 22:6 (7.8%)]. Injection in the brain ventricle of radioactive glucose, the major source of acetyl‐CoA in the CNS, revealed that glucose was a precursor of saturated (85%) and monounsaturated (15%) but not of polyunsaturated fatty acids. Thus, this study demonstrated distinct fates of glucose and acetyl‐l‐carnitine following intracerebroventricular injection. In summary, these data implicate acetyl‐l‐carnitine as an important member of a complex acetate trafficking system in brain lipid metabolism.

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.Keywords: acetyl-l-carnitine; NMR spectroscopy; carbon-13; cholesterol; lipogenesis.Acetyl-l-carnitine is a major esterified carnitine congener in most mammalian tissues [1,2]. It is synthesized by carnitine O-acetyltransferase reaction (EC 2.3.1.7), which reversibly converts acetylCoA and free carnitine to acetyl-l-carnitine and CoASH without ATP utilization. Carnitine O-acetyltransferase activity was reported to be present almost in all tissues [3,4], and in the liver, it was found in peroxisomes, mitochondria, and microsomes [5,6].Previous investigations on acetyl-l-carnitine metabolism have focused on its role in energy-producing processes [7,8]. Evidence has been also presented that supports the conclusion that the acetylcarnitine/carnitine system buffers the CoASH/acetylCoA ratio in the mitochondrial matrix [9].To date, however, no detailed study has investigated both the role of acetyl-l-carnitine in acetyl groups trafficking between intracellular organelles and its involvement in oxidative and biosynthetic processes in vivo.As a product of peroxisomal b-oxidation, acetyl-l-carnitine may be shuttled out from peroxisomes to the cytosol [10,11], while the acetylCoA synthesized in mitochondria by glucose or fatty acid oxidation may be transported to the cytosolic compartment as acetyl-l-carnitine both in liver [12,13] and heart myocytes [14]. Studies on exogenous administration of ([1-14 C]acetyl)-l-carnitine in 24-h fasted mice reported that most acetyl moiety was oxidized in mitochondria and radioactivity was released as 14 CO 2 [15]. Moreover, the liposoluble fraction o...

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