Carnitine-acylcarnitine translocase

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solute carrier family 25 (carnitine/acylcarnitine translocase), member 20
Identifiers
SymbolSLC25A20
Alt. symbolsCACT
NCBI gene788
HGNC1421
OMIM212138
RefSeqNM_000387
UniProtO43772
Other data
LocusChr. 3 p21.31

Carnitine-acylcarnitine translocase (CACT) is responsible for passive transport of carnitine and carnitine-fatty acid complexes and across the inner mitochondrial membrane as part of the carnitine shuttle system.

Function[edit]

Fatty acyl–carnitine can diffuse from the cytosol across the porous outer mitochondrial membrane to the intermembrane space, but must utilize CACT to cross the nonporous inner mitochondrial membrane and reach the mitochondrial matrix. CACT is a cotransporter, returning one molecule of carnitine from the matrix to the intermembrane space as one molecule of fatty acyl–carnitine moves into the matrix.[1]

Clinical significance[edit]

A disorder is associated with carnitine-acylcarnitine translocase deficiency. This disorder disrupts the carnitine shuttle system from moving fatty acids across the mitochondrial membrane, leading to a decrease in fatty acid catabolism. The result is an accumulation of fatty acid within muscles and liver, decreased tolerance to long term exercise, inability to fast for more than a few hours, muscle weakness and wasting, and a strong acidic smell on the breath (due to protein catabolism).

Acyl-CoA from cytosol to the mitochondrial matrix

Model organisms[edit]

Model organisms have been used in the study of SLC25A20 function. A conditional knockout mouse line called Slc25a20tm1a(EUCOMM)Wtsi was generated at the Wellcome Trust Sanger Institute.[2] Male and female animals underwent a standardized phenotypic screen[3] to determine the effects of deletion.[4][5][6][7] Additional screens performed: - In-depth immunological phenotyping[8]

References[edit]

  1. ^ "Principles of biochemistry, 2nd edition, edited by Albert Lehninger, David Nelson, and Michael Cox, Worth Publishers, Inc., New York, 1992, 1012 pp, $67.95". Molecular Reproduction and Development. 37 (4): 477. April 1994. doi:10.1002/mrd.1080370421. ISSN 1040-452X.
  2. ^ Gerdin AK (2010). "The Sanger Mouse Genetics Programme: high throughput characterisation of knockout mice". Acta Ophthalmologica. 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x. S2CID 85911512.
  3. ^ a b "International Mouse Phenotyping Consortium".
  4. ^ Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A (Jun 2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–42. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
  5. ^ Dolgin E (Jun 2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
  6. ^ Collins FS, Rossant J, Wurst W (Jan 2007). "A mouse for all reasons". Cell. 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247. S2CID 18872015.
  7. ^ White JK, Gerdin AK, Karp NA, Ryder E, Buljan M, Bussell JN, Salisbury J, Clare S, Ingham NJ, Podrini C, Houghton R, Estabel J, Bottomley JR, Melvin DG, Sunter D, Adams NC, Sanger Institute Mouse Genetics Project, Tannahill D, Logan DW, Macarthur DG, Flint J, Mahajan VB, Tsang SH, Smyth I, Watt FM, Skarnes WC, Dougan G, Adams DJ, Ramirez-Solis R, Bradley A, Steel KP (2013). "Genome-wide generation and systematic phenotyping of knockout mice reveals new roles for many genes". Cell. 154 (2): 452–64. doi:10.1016/j.cell.2013.06.022. PMC 3717207. PMID 23870131.
  8. ^ a b "Infection and Immunity Immunophenotyping (3i) Consortium".[permanent dead link]