[Physiological functions of carnitine and carnitine transporters in the central nervous system].
L-Carnitine is an essential co-factor in the metabolism of lipids and consequently in the production of cellular energy. This molecule has important physiological roles, including its involvement in the beta-oxidation of fatty acids by facilitating the transport of long-chain fatty acids across the mitochondrial inner membrane as acylcarnitine esters. In the brain, L-carnitine and acetyl-L-carnitine have important roles in cerebral bioenergetics and in neuroprotection through a variety of mechanisms including their antioxidant properties and in the modulation and promotion of synaptic neurotransmission, most notably cholinergic neurotransmission. Acetyl-L-carnitine was successfully applied as pharmacological agents for treatment of chronic degenerative diseases of the senile brain and for slowing down the progression of mental deterioration in Alzheimer's disease, and they may involve both the cholinergic neuronal transmission activity of acetyl-L-carnitine and its ability to enhance neuronal metabolism in mitochondria. Astrocytes are able to produce large amounts of ketone bodies, which are thought to supply adjacent neurons with easily transferable substrates for generation of energy. Thus, the L-carnitine uptake mechanism becomes the rate-limiting step for astrocyte ketogenesis. Several carnitine transporters have been known to be present in peripheral tissues. In this review, the functional expression and physiological role of carnitine transporters in central nervous system is further discussed.
Inazu
Masato
M
Department of Pharmacology, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo 160-8402, Japan. inazu@tokyo-med.ac.jp
Matsumiya
Teruhiko
T
D000108:Acetylcarnitine / Q000502:physiology / Q000627:therapeutic use; D000544:Alzheimer Disease / Q000188:drug therapy; D001253:Astrocytes / Q000378:metabolism; D001921:Brain / Q000502:physiology*; D002331:Carnitine / Q000378:metabolism* / Q000502:physiology*; D002794:Choline / Q000502:physiology; D004734:Energy Metabolism; D007657:Ketone Bodies / Q000096:biosynthesis; D050356:Lipid Metabolism; D008928:Mitochondria / Q000378:metabolism; D027701:Organic Cation Transport Proteins / Q000502:physiology*; D009435:Synaptic Transmission
D007657:Ketone Bodies; D027701:Organic Cation Transport Proteins; C467737:SLC22A16 protein, human; D000108:Acetylcarnitine; D002794:Choline; D002331:Carnitine