Carnitine-acylcarnitine translocase: Difference between revisions

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==Function==
==Function==
This enzyme is required since fatty acids cannot cross the mitochondrial membranes without assistance. The fatty acid is firstly bound to [[Coenzyme A|CoA]] and may cross the external mitochondrial membrane. It then exchanges the CoA for [[carnitine]] by the action of the enzyme [[carnitine palmitoyltransferase I]]. The complex then enters the mitochondrial matrix via facilitated diffusion by '''carnitine-acylcarnitine translocase'''. Here, the acyl-cartinine complex is disrupted by [[carnitine palmitoyltransferase II]] and the fatty acid rebinds to CoA. Carnitine then diffuses back across the membrane by '''carnitine-acylcarnitine translocase''' into the mitochondrial intermembrane space. This is called the carnitine shuttle system.
This enzyme is required since fatty acids cannot cross the mitochondrial membranes without assistance. The fatty acid is firstly bound to [[Coenzyme A|CoA]] and may cross the external mitochondrial membrane. It then exchanges the CoA for [[carnitine]] by the action of the enzyme [[carnitine palmitoyltransferase I]]. The complex then enters the mitochondrial matrix via facilitated diffusion by '''carnitine-acylcarnitine translocase'''. Here, the acyl-carnitine complex is disrupted by [[carnitine palmitoyltransferase II]] and the fatty acid rebinds to CoA. Carnitine then diffuses back across the membrane by '''carnitine-acylcarnitine translocase''' into the mitochondrial intermembrane space. This is called the carnitine shuttle system.


==Clinical significance==
==Clinical significance==
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==Model organisms==
==Model organisms==
[[Model organism]]s have been used in the study of SLC25A20 function. A conditional [[knockout mouse]] line called ''Slc25a20<sup>tm1a(EUCOMM)Wtsi</sup>'' was generated at the [[Wellcome Trust Sanger Institute]].<ref name="mgp_reference">{{cite journal |title=The Sanger Mouse Genetics Programme: high throughput characterisation of knockout mice |author=Gerdin AK |year=2010 |journal=Acta Ophthalmologica|volume=88 |pages=925–7|doi=10.1111/j.1755-3768.2010.4142.x }}</ref> Male and female animals underwent a standardized [[phenotypic screen]]<ref name="IMPCsearch_ref">{{cite web |url=http://www.mousephenotype.org/data/search?q=Slc25a20#fq=*:*&facet=gene |title=International Mouse Phenotyping Consortium}}</ref> to determine the effects of deletion.<ref name="pmid21677750">{{cite journal | vauthors = 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 | title = A conditional knockout resource for the genome-wide study of mouse gene function | journal = Nature | volume = 474 | issue = 7351 | pages = 337–42 | date = Jun 2011 | pmid = 21677750 | pmc = 3572410 | doi = 10.1038/nature10163 }}</ref><ref name="mouse_library">{{cite journal | vauthors = Dolgin E | title = Mouse library set to be knockout | journal = Nature | volume = 474 | issue = 7351 | pages = 262–3 | date = Jun 2011 | pmid = 21677718 | doi = 10.1038/474262a }}</ref><ref name="mouse_for_all_reasons">{{cite journal | vauthors = Collins FS, Rossant J, Wurst W | title = A mouse for all reasons | journal = Cell | volume = 128 | issue = 1 | pages = 9–13 | date = Jan 2007 | pmid = 17218247 | doi = 10.1016/j.cell.2006.12.018 }}</ref><ref name="pmid23870131">{{cite journal | vauthors = 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 | title = Genome-wide generation and systematic phenotyping of knockout mice reveals new roles for many genes | journal = Cell | volume = 154 | issue = 2 | pages = 452–64 | year = 2013 | pmid = 23870131 | doi = 10.1016/j.cell.2013.06.022 | pmc=3717207}}</ref> Additional screens performed:  - In-depth immunological phenotyping<ref name="iii_ref">{{cite web |url= http://www.immunophenotyping.org/data/search?keys=Slc25a20&field_gene_construct_tid=All |title=Infection and Immunity Immunophenotyping (3i) Consortium}}</ref>  
[[Model organism]]s have been used in the study of SLC25A20 function. A conditional [[knockout mouse]] line called ''Slc25a20<sup>tm1a(EUCOMM)Wtsi</sup>'' was generated at the [[Wellcome Trust Sanger Institute]].<ref name="mgp_reference">{{cite journal |title=The Sanger Mouse Genetics Programme: high throughput characterisation of knockout mice |author=Gerdin AK |year=2010 |journal=Acta Ophthalmologica|volume=88 |pages=925–7|doi=10.1111/j.1755-3768.2010.4142.x }}</ref> Male and female animals underwent a standardized [[phenotypic screen]]<ref name="IMPCsearch_ref">{{cite web |url=http://www.mousephenotype.org/data/search?q=Slc25a20#fq=*:*&facet=gene |title=International Mouse Phenotyping Consortium}}</ref> to determine the effects of deletion.<ref name="pmid21677750">{{cite journal | vauthors = 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 | title = A conditional knockout resource for the genome-wide study of mouse gene function | journal = Nature | volume = 474 | issue = 7351 | pages = 337–42 | date = Jun 2011 | pmid = 21677750 | pmc = 3572410 | doi = 10.1038/nature10163 }}</ref><ref name="mouse_library">{{cite journal | vauthors = Dolgin E | title = Mouse library set to be knockout | journal = Nature | volume = 474 | issue = 7351 | pages = 262–3 | date = Jun 2011 | pmid = 21677718 | doi = 10.1038/474262a }}</ref><ref name="mouse_for_all_reasons">{{cite journal | vauthors = Collins FS, Rossant J, Wurst W | title = A mouse for all reasons | journal = Cell | volume = 128 | issue = 1 | pages = 9–13 | date = Jan 2007 | pmid = 17218247 | doi = 10.1016/j.cell.2006.12.018 }}</ref><ref name="pmid23870131">{{cite journal | vauthors = 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 | title = Genome-wide generation and systematic phenotyping of knockout mice reveals new roles for many genes | journal = Cell | volume = 154 | issue = 2 | pages = 452–64 | year = 2013 | pmid = 23870131 | doi = 10.1016/j.cell.2013.06.022 | pmc=3717207}}</ref> Additional screens performed:  - In-depth immunological phenotyping<ref name="iii_ref">{{cite web |url= http://www.immunophenotyping.org/data/search?keys=Slc25a20&field_gene_construct_tid=All |title= Infection and Immunity Immunophenotyping (3i) Consortium }}{{Dead link|date=November 2018 |bot=InternetArchiveBot |fix-attempted=yes }}</ref>  
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|+ ''Slc25a20'' knockout mouse phenotype
|+ ''Slc25a20'' knockout mouse phenotype

Latest revision as of 16:30, 20 November 2018

solute carrier family 25 (carnitine/acylcarnitine translocase), member 20
Identifiers
SymbolSLC25A20
Alt. symbolsCACT
Entrez788
HUGO1421
OMIM212138
RefSeqNM_000387
UniProtO43772
Other data
LocusChr. 3 p21.31

Carnitine-acylcarnitine translocase is responsible for transporting both carnitine-fatty acid complexes and carnitine across the inner mitochondrial membrane.

Function

This enzyme is required since fatty acids cannot cross the mitochondrial membranes without assistance. The fatty acid is firstly bound to CoA and may cross the external mitochondrial membrane. It then exchanges the CoA for carnitine by the action of the enzyme carnitine palmitoyltransferase I. The complex then enters the mitochondrial matrix via facilitated diffusion by carnitine-acylcarnitine translocase. Here, the acyl-carnitine complex is disrupted by carnitine palmitoyltransferase II and the fatty acid rebinds to CoA. Carnitine then diffuses back across the membrane by carnitine-acylcarnitine translocase into the mitochondrial intermembrane space. This is called the carnitine shuttle system.

Clinical significance

A disorder is associated with carnitine-acylcarnitine translocase deficiency. This disorder prevents the shuttle-like action of carnitine from assisting fatty acids across the mitochondrial membrane and therefore there is decreased fatty acid catabolism. The result of this is an increased number of fat droplets 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 breakdown).

File:Acyl-CoA from cytosol to the mitochondrial matrix.svg
Acyl-CoA from cytosol to the mitochondrial matrix

Model organisms

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.[1] Male and female animals underwent a standardized phenotypic screen[2] to determine the effects of deletion.[3][4][5][6] Additional screens performed: - In-depth immunological phenotyping[7]

References

  1. ↑ 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.
  2. ↑ 2.0 2.1 "International Mouse Phenotyping Consortium".
  3. ↑ 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.
  4. ↑ Dolgin E (Jun 2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
  5. ↑ 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.
  6. ↑ 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.
  7. ↑ 7.0 7.1 "Infection and Immunity Immunophenotyping (3i) Consortium".[permanent dead link]


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