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Acyl-CoA synthetase

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Acyl-CoA synthetases, also known as acyl-CoA ligases, are enzymes that “activate” fatty acids by thioesterification to CoA.[1] It represents the initial step of fatty acid metabolism so that fatty acids can participate in catabolic and anabolic pathways.[1] Among these are, for example, the synthesis of triacylglycerol, phospholipids, plasmalogens, sphingolipids, the degradation of fatty acids for energy production, the conversion to alcohols or aldehydes, the elongation of fatty acids, the insertion and removal of double bonds or the covalent binding to proteins.[1][2]

The members of this family mainly activate fatty acids, but there are also members that activate other substrates instead, such as AACS, which activates acetoacetic acid, or ACSF3, which activates methylmalonic acid and malonic acid.[3][4]

Reaction

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Acyl-CoA synthetases catalyze fatty acid activation, which consists of 2 steps:[1]

First, an ATP-dependent adenylation and release of pyrophophates takes place.[1]

In the 2nd step, CoA-SH displaces the adenylate group, which is released as AMP, and forms a thioester bond with the substrate.[1]

In summary:

Members

[edit]
Symbol Name Localization Preferred substrate Product Gene defect Prevalence
Short-chain ACS family[1]
ACSS1[5] Acyl-CoA synthetase short-chain family member 1 Mitochondrion[5] Acetate[5] Acetyl-CoA[5]
ACSS2[6] Acyl-CoA synthetase short-chain family member 2 Cytosol[6] Acetate[6] Acetyl-CoA[6]
ACSS3[7] Acyl-CoA synthetase short-chain family member 3 Cytosol, mitochondrial matrix[7] Acetate Acetyl-CoA
Medium-chain ACS family[1] (C6-C10)
ACSM1[8] Acyl-CoA synthetase medium-chain family member 1 Mitochondrial matrix[8]
ACSM2A[9] Acyl-CoA synthetase medium-chain family member 2A Mitochondrion[9] Medium chain fatty acids
ACSM2B[10] Acyl-CoA synthetase medium-chain family member 2B Mitochondrion[10]
ACSM3[11] Acyl-CoA synthetase medium-chain family member 3 Mitochondrion[11]
ACSM4[12] Acyl-CoA synthetase medium-chain family member 4 Mitochondrial matrix (predicted)[12] Decanoate-CoA (predicted)[12]
ACSM5[13] Acyl-CoA synthetase medium-chain family member 5 Mitochondrial matrix (predicted)[13]
ACSM6[14] Acyl-CoA synthetase medium-chain family member 6 Mitochondrial Matrix (predicted)[14]
Long-chain ACS family[1]
ACSL1[15] Acyl-CoA synthetase long-chain family member 1 Free long-chain fatty acids[15] Fatty acyl-CoA esters[15]
ACSL3[16] Acyl-CoA synthetase long-chain family member 3 Myristate[16], arachidonate[16], eicosapentaenoate[16]
ACSL4[17] Acyl-CoA synthetase long-chain family member 4 Peroxisome[2] Arachidonate[17] Intellectual developmental disorder, X-linked 63[18]
ACSL5[19] Acyl-CoA synthetase long-chain family member 5
ACSL6[20] Acyl-CoA synthetase long-chain family member 6
Very long-chain ACS family[1] (>C22)
SLC27A1[21] Solute carrier family 27 (fatty acid transporter), member 1 Plasma membrane[21], Endoplasmic reticulum
SLC27A2[22] Solute carrier family 27 (fatty acid transporter), member 2 Endoplasmic reticulum[22], peroxisome[22][2] Long-chain, branched-chain and very long-chain fatty acids[22] Fatty acyl-CoA esters[22]
SLC27A3[23] Solute carrier family 27 (fatty acid transporter), member 3
SLC27A4[24] Solute carrier family 27 (fatty acid transporter), member 4 Peroxisome[2] Ichthyosis prematurity syndrome[24]
SLC27A5[25] Solute carrier family 27 (fatty acid transporter), member 5 Endoplasmic reticulum[25] Very long-chain fatty-acids containing 24- and 26-carbons[25]
SLC27A6[26] Solute carrier family 27 (fatty acid transporter), member 6
Bubblegum ACS family[1]
ACSBG1[27] Acyl-CoA synthetase bubblegum family member 1
ACSBG2[28] Acyl-CoA synthetase bubblegum family member 2 Cytosol[28], Mitochondrion[28]
Other ACSs [1]
AACS[3] Acetoacetyl-CoA synthetase Cytosol (predicted)[3] Acetoacetate[3] Acetoacetyl-CoA (predicted)[3]
ACSF2[29] Acyl-CoA synthetase family member 2 Mitochondrion[29]
ACSF3[4] Acyl-CoA synthetase family member 3 Mitochondrion[4] Malonate[4], methylmalonate[4] Malonyl-CoA, methylmalonyl-CoA Combined malonic and methylmalonic aciduria (CMAMMA)[4] 1: 30,000[30]
AASDH[31] Aminoadipate-semialdehyde dehydrogenase

References

[edit]
  1. ^ a b c d e f g h i j k l Watkins, Paul A.; Maiguel, Dony; Jia, Zhenzhen; Pevsner, Jonathan (December 2007). "Evidence for 26 distinct acyl-coenzyme A synthetase genes in the human genome". Journal of Lipid Research. 48 (12): 2736–2750. doi:10.1194/jlr.m700378-jlr200. ISSN 0022-2275. PMID 17762044.
  2. ^ a b c d Watkins, Paul A.; Ellis, Jessica M. (September 2012). "Peroxisomal acyl-CoA synthetases". Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. 1822 (9): 1411–1420. doi:10.1016/j.bbadis.2012.02.010. PMC 3382043. PMID 22366061.
  3. ^ a b c d e "AACS acetoacetyl-CoA synthetase [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2024-10-19.
  4. ^ a b c d e f "ACSF3 acyl-CoA synthetase family member 3 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2024-10-19.
  5. ^ a b c d "ACSS1 acyl-CoA synthetase short chain family member 1 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2024-10-19.
  6. ^ a b c d "ACSS2 acyl-CoA synthetase short chain family member 2 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2024-10-19.
  7. ^ a b "ACSS3 acyl-CoA synthetase short chain family member 3 [Homo sapiens (human)] - Gene - NCBI"". www.ncbi.nlm.nih.gov. Retrieved 2024-10-19.
  8. ^ a b "ACSM1 acyl-CoA synthetase medium chain family member 1 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2024-10-19.
  9. ^ a b "ACSM2A acyl-CoA synthetase medium chain family member 2A [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2024-10-19.
  10. ^ a b "ACSM2B acyl-CoA synthetase medium chain family member 2B [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2024-10-19.
  11. ^ a b "ACSM3 acyl-CoA synthetase medium chain family member 3 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2024-10-19.
  12. ^ a b c "ACSM4 acyl-CoA synthetase medium chain family member 4 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2024-10-19.
  13. ^ a b "ACSM5 acyl-CoA synthetase medium chain family member 5 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2024-10-19.
  14. ^ a b "ACSM6 acyl-CoA synthetase medium chain family member 6 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2024-10-19.
  15. ^ a b c "ACSL1 acyl-CoA synthetase long chain family member 1 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2024-10-19.
  16. ^ a b c d "ACSL3 acyl-CoA synthetase long chain family member 3 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2024-10-19.
  17. ^ a b "ACSL4 acyl-CoA synthetase long chain family member 4 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2024-10-19.
  18. ^ "Entry - *300157 - ACYL-CoA SYNTHETASE LONG CHAIN FAMILY, MEMBER 4; ACSL4 - OMIM". omim.org. Retrieved 2024-10-19.
  19. ^ "ACSL5 acyl-CoA synthetase long chain family member 5 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2024-10-19.
  20. ^ "ACSL6 acyl-CoA synthetase long chain family member 6 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2024-10-19.
  21. ^ a b "SLC27A1 solute carrier family 27 member 1 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2024-10-19.
  22. ^ a b c d e "SLC27A2 solute carrier family 27 member 2 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2024-10-19.
  23. ^ "SLC27A3 solute carrier family 27 member 3 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2024-10-19.
  24. ^ a b "SLC27A4 solute carrier family 27 member 4 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2024-10-19.
  25. ^ a b c "SLC27A5 solute carrier family 27 member 5 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2024-10-19.
  26. ^ "SLC27A6 solute carrier family 27 member 6 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2024-10-19.
  27. ^ "ACSBG1 acyl-CoA synthetase bubblegum family member 1 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2024-10-19.
  28. ^ a b c "ACSBG2 acyl-CoA synthetase bubblegum family member 2 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2024-10-19.
  29. ^ a b "ACSF2 acyl-CoA synthetase family member 2 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2024-02-02.
  30. ^ NIH Intramural Sequencing Center Group; Sloan, Jennifer L; Johnston, Jennifer J; Manoli, Irini; Chandler, Randy J; Krause, Caitlin; Carrillo-Carrasco, Nuria; Chandrasekaran, Suma D; Sysol, Justin R; O'Brien, Kevin; Hauser, Natalie S; Sapp, Julie C; Dorward, Heidi M; Huizing, Marjan; Barshop, Bruce A (September 2011). "Exome sequencing identifies ACSF3 as a cause of combined malonic and methylmalonic aciduria". Nature Genetics. 43 (9): 883–886. doi:10.1038/ng.908. ISSN 1061-4036. PMC 3163731. PMID 21841779.
  31. ^ "AASDH aminoadipate-semialdehyde dehydrogenase [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2024-10-19.
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