|Gene:||Cact||Accession Number: G-11019 (MetaCyc)|
Synonyms: Slc25a20, carnitine/acylcarnitine carrier, mitochondrial carnitine carrier protein, mitochondrial carnitine/acylcarnitine carrier protein, CAC
Species: Rattus norvegicus
This transport protein is a component of the mitochondrial L-carnitine shuttle. It is located in the inner mitochondrial membrane and catalyzes the translocation of O-acylcarnitines synthesized in the cytosol into the mitochondrial matrix (lumen) in exchange for free carnitine (in [Indiveri98, Giangregorio07]). It provides a mechanism for transport of O-acyl-L-carnitine esters of long-chain fatty acids through the inner mitochondrial membrane for subsequent β-oxidation in the matrix. Intramitochondrial L-carnitine, O-acetylcarnitine, and short-chain O-acyl-L-carnitines can also be transported out of the mitochondrial lumen by this protein [Ramsay75] and reviewed in [Ramsay01, Vaz02].
In humans, a deficiency of this protein results in a life-threatening disorder of mitochondrial fatty acid β-oxidation [Lopriore01].
Locations: mitochondrial inner membrane, peroxisome
Molecular Weight of Polypeptide: 33.154 kD (from nucleotide sequence), 32.5 kD (experimental) [Indiveri90 ]
|Cellular Component:||GO:0005743 - mitochondrial inner membrane
GO:0005777 - peroxisome [Fraser99c]
Enzymatic reaction of: carnitine-acylcarnitine translocase
Recombinant protein has also been overexpressed in Escherichia coli, purified and characterized after reconstitution into liposomes. It was found to have transport properties identical to the native transporter. It transported L-carnitine and carnitine esters of various chain lengths. Kinetic parameters were determined. Transport was inhibited by maleimides, mercurials and sulfobetaines [Indiveri98]. Structure-function studies have been performed using site-directed mutagenesis. This carrier catalyzes carnitine/acylcarnitine and carnitine/carnitine antiport, as well as a less efficient carnitine uniport in the absence of a counter-substrate. A ping-pong transport mechanism for both exchanges has been shown [Giangregorio07, Pande80]. Reviewed in [Ramsay01].
Giangregorio07: Giangregorio N, Tonazzi A, Indiveri C, Palmieri F (2007). "Conformation-dependent accessibility of Cys-136 and Cys-155 of the mitochondrial rat carnitine/acylcarnitine carrier to membrane-impermeable SH reagents." Biochim Biophys Acta 1767(11);1331-9. PMID: 17961500
Indiveri91: Indiveri C, Tonazzi A, Prezioso G, Palmieri F (1991). "Kinetic characterization of the reconstituted carnitine carrier from rat liver mitochondria." Biochim Biophys Acta 1065(2);231-8. PMID: 2059655
Indiveri91a: Indiveri C, Tonazzi A, Palmieri F (1991). "Characterization of the unidirectional transport of carnitine catalyzed by the reconstituted carnitine carrier from rat liver mitochondria." Biochim Biophys Acta 1069(1);110-6. PMID: 1932043
Indiveri97: Indiveri C, Iacobazzi V, Giangregorio N, Palmieri F (1997). "The mitochondrial carnitine carrier protein: cDNA cloning, primary structure and comparison with other mitochondrial transport proteins." Biochem J 321 ( Pt 3);713-9. PMID: 9032458
Indiveri98: Indiveri C, Iacobazzi V, Giangregorio N, Palmieri F (1998). "Bacterial overexpression, purification, and reconstitution of the carnitine/acylcarnitine carrier from rat liver mitochondria." Biochem Biophys Res Commun 249(3);589-94. PMID: 9731180
Lopriore01: Lopriore E, Gemke RJ, Verhoeven NM, Jakobs C, Wanders RJ, Roeleveld-Versteeg AB, Poll-The BT (2001). "Carnitine-acylcarnitine translocase deficiency: phenotype, residual enzyme activity and outcome." Eur J Pediatr 160(2);101-4. PMID: 11271379
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