MetaCyc Transporter: carnitine-acylcarnitine translocase

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].

This protein is a member of the mitochondrial substrate carrier family [Indiveri97]. It has been identified in both mitochondria and peroxisomes of rat liver [Fraser99a].

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 ]

Unification Links: Pride:P97521 , Protein Model Portal:P97521 , String:10116.ENSRNOP00000027520 , UniProt:P97521

Relationship Links: Entrez-Nucleotide:PART-OF:X97831 , InterPro:IN-FAMILY:IPR018108 , InterPro:IN-FAMILY:IPR023395 , PDB:Structure:2BMN , Pfam:IN-FAMILY:PF00153 , Prosite:IN-FAMILY:PS50920

Gene-Reaction Schematic: ?

Gene-Reaction Schematic

GO Terms:

Cellular Component: GO:0005743 - mitochondrial inner membrane [Ramsay01]
GO:0005777 - peroxisome [Fraser99a]

Created 25-Nov-2008 by Fulcher CA , SRI International

Enzymatic reaction of: carnitine-acylcarnitine translocase

Transport reaction diagram for carnitine-acylcarnitine translocase

The protein has been purified from rat liver mitochondria, reconstituted into liposomes, and its activity characterized [Indiveri90, Indiveri91, Indiveri91a].

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].

Inhibitors (Unknown Mechanism): lauryl sulfobetaine [Indiveri98] , p-hydroxymercuribenzoate [Indiveri98] , N-ethylmaleimide [Indiveri98]


Fraser99a: Fraser F, Zammit VA (1999). "Submitochondrial and subcellular distributions of the carnitine-acylcarnitine carrier." FEBS Lett 445(1);41-4. PMID: 10069371

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

Indiveri90: Indiveri C, Tonazzi A, Palmieri F (1990). "Identification and purification of the carnitine carrier from rat liver mitochondria." Biochim Biophys Acta 1020(1);81-6. PMID: 2223786

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

Pande80: Pande SV, Parvin R (1980). "Carnitine-acylcarnitine translocase catalyzes an equilibrating unidirectional transport as well." J Biol Chem 255(7);2994-3001. PMID: 7358722

Ramsay01: Ramsay RR, Gandour RD, van der Leij FR (2001). "Molecular enzymology of carnitine transfer and transport." Biochim Biophys Acta 1546(1);21-43. PMID: 11257506

Ramsay75: Ramsay RR, Tubbs PK (1975). "The mechanism of fatty acid uptake by heart mitochondria: an acylcarnitine-carnitine exchange." FEBS Lett 54(1);21-5. PMID: 1132491

Vaz02: Vaz FM, Wanders RJ (2002). "Carnitine biosynthesis in mammals." Biochem J 361(Pt 3);417-29. PMID: 11802770

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Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
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