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Current Chemical Biology


ISSN (Print): 2212-7968
ISSN (Online): 1872-3136

The Carnitine Transporter Network: Interactions with Drugs

Author(s): Cesare Indiveri, Lorena Pochini, Francesca Oppedisano and Annamaria Tonazzi

Volume 4, Issue 2, 2010

Page: [108 - 123] Pages: 16

DOI: 10.2174/2212796811004020108

Price: $65


Carnitine homeostasis has a pivotal role in the life of mammals. It is realized by the carnitine system, which consists of networks of enzymes and membrane transporters and plays an essential role in functions such as the regulation of the CoA/acyl-CoA ratio, the supply of substrates for the β-oxidation to mitochondria and peroxisomes and of acyl units for VLDL assembly to the ER, the efflux of acetyl groups from mitochondria during glucose metabolism and the detoxification of the organism. The network of the transporters plays a crucial role in maintaining homeostasis since it allows the absorption, excretion and re-absorption of carnitine and carnitine derivatives as well as the flux of these metabolites through different tissues and within sub-cellular compartments. Several transport systems which were thought to be involved in the network have been identified and characterized to a certain extent. These are the plasma membrane transporters OCTN1, 2 and 3, the mitochondrial CACT and the carnitine transport system of endoplasmic reticulum (ERCT). These transporters have been functionally characterized by studies in eukaryotic cell systems and/or in reconstituted liposomes. Interestingly, it was found that some commonly used drugs interact with different carnitine transporters, causing alterations of the transport function by displacing the substrate from the binding site or by irreversibly inactivating the transporters. These interactions will cause derangements of the carnitine homeostasis. The current knowledge of the characterization of the carnitine transporter network and the interaction with drugs are reviewed with emphasis to the most recent data obtained using the proteoliposome reconstituted systems.

Keywords: Carnitine, transporter, homeostasis, drugs

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