Acyl-CoA synthetase

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Acyl-CoA synthetases, also known as acyl-CoA ligases, are enzymes that "activate" fatty acids by thioester ification to coenzyme A. [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]

Contents

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

Reaction

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

SymbolNameLocalization EC number Preferred substrate Product Enzyme defect Prevalence
Short-chain acyl-CoA synthetase family [1]
ACSS1 [5] Acyl-CoA synthetase short-chain family member 1 Mitochondrion [5]

EC 6.2.1.1 [5] EC 6.2.1.17 [5]

Acetate [5] Acetyl-CoA [5]
ACSS2 [6] Acyl-CoA synthetase short-chain family member 2 Cytosol [6]

EC 6.2.1.1 [6] EC 6.2.1.17 [6]

Acetate [6] Acetyl-CoA [6]
ACSS3 [7] Acyl-CoA synthetase short-chain family member 3 Mitochondrial matrix [7]

EC 6.2.1.1 [7] EC 6.2.1.17 [7]

Propionate Propionyl-CoA
Medium-chain acyl-CoA synthetase family [1] (C6-C10)
ACSM1 [8] Acyl-CoA synthetase medium-chain family member 1 Mitochondrial matrix [8]

EC 6.2.1.2 [8] EC 6.2.1.25 [8]

ACSM2A [9] Acyl-CoA synthetase medium-chain family member 2A Mitochondrion [9]

EC 6.2.1.2 [9] EC 6.2.1.25 [9]

Medium chain fatty acids
ACSM2B [10] Acyl-CoA synthetase medium-chain family member 2B Mitochondrion [10]

EC 6.2.1.2 [10] EC 6.2.1.25 [10]

ACSM3 [11] Acyl-CoA synthetase medium-chain family member 3 Mitochondrion [11]

EC 6.2.1.17 [11] EC 6.2.1.2 [11]

ACSM4 [12] Acyl-CoA synthetase medium-chain family member 4 Mitochondrion [12]

EC 6.2.1.2 [12]

Decanoate-CoA (predicted) [12]
ACSM5 [13] Acyl-CoA synthetase medium-chain family member 5 Mitochondrion [13]

EC 6.2.1.2 [13]

ACSM6 [14] Acyl-CoA synthetase medium-chain family member 6 Mitochondrion [14]

EC 6.2.1.2 [14]

Long-chain acyl-CoA synthetase family [1]
ACSL1 [15] Acyl-CoA synthetase long-chain family member 1

EC 6.2.1.15 [15] EC 6.2.1.24 [15] EC 6.2.1.3 [15]

Free long-chain fatty acids [15] Fatty acyl-CoA esters [15]
ACSL3 [16] Acyl-CoA synthetase long-chain family member 3

EC 6.2.1.15 [16] EC 6.2.1.2 [16] EC 6.2.1.3 [16]

Myristate, [16] arachidonate, [16] eicosapentaenoate [16]
ACSL4 [17] Acyl-CoA synthetase long-chain family member 4 Peroxisome [2]

EC 6.2.1.15 [17] EC 6.2.1.3 [17]

Arachidonate [17] Intellectual developmental disorder, X-linked 63 [18]
ACSL5 [19] Acyl-CoA synthetase long-chain family member 5

EC 6.2.1.15 [19] EC 6.2.1.3 [19]

ACSL6 [20] Acyl-CoA synthetase long-chain family member 6

EC 6.2.1.15 [20] EC 6.2.1.3 [20]

Very long-chain acyl-CoA synthetase family [1] (>C22)
SLC27A1 [21] Solute carrier family 27 (fatty acid transporter), member 1 Plasma membrane [21]

EC 6.2.1.15 [21] EC 6.2.1.3 [21]

SLC27A2 [22] Solute carrier family 27 (fatty acid transporter), member 2 Endoplasmic reticulum, [22] peroxisome [22] [2]

EC 6.2.1.15 [22] EC 6.2.1.24 [22] EC 6.2.1.3 [22] EC 6.2.1.7 [22]

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

EC 6.2.1.15 [23] EC 6.2.1.3 [23]

SLC27A4 [24] Solute carrier family 27 (fatty acid transporter), member 4 Peroxisome [2]

EC 6.2.1.15 [24] EC 6.2.1.3 [24]

Ichthyosis prematurity syndrome [24]
SLC27A5 [25] Solute carrier family 27 (fatty acid transporter), member 5 Endoplasmic reticulum [25]

EC 6.2.1.3 [25] EC 6.2.1.7 [25]

Very long-chain fatty-acids containing 24- and 26-carbons [25]
SLC27A6 [26] Solute carrier family 27 (fatty acid transporter), member 6

EC 6.2.1.15 [26] EC 6.2.1.3 [26]

Bubblegum acyl-CoA synthetase family [1]
ACSBG1 [27] Acyl-CoA synthetase bubblegum family member 1

EC 6.2.1.3 [27]

ACSBG2 [28] Acyl-CoA synthetase bubblegum family member 2 Cytosol, [28] Mitochondrion [28]

EC 6.2.1.15 [28] EC 6.2.1.3 [28]

Other acyl-CoA synthetases [1]
AACS [3] Acetoacetyl-CoA synthetase Cytosol (predicted) [3]

EC 6.2.1.16 [3]

Acetoacetate [3] Acetoacetyl-CoA (predicted) [3]
ACSF2 [29] Acyl-CoA synthetase family member 2 Mitochondrion [29]

EC 6.2.1.2 [29]

ACSF3 [4] Acyl-CoA synthetase family member 3 Mitochondrion [4]

EC 6.2.1.76 [4]

Malonate, [4] methylmalonate, [4] lignocerate [1] Malonyl-CoA, methylmalonyl-CoA Combined malonic and methylmalonic aciduria (CMAMMA) [4] 1: 30,000 [30]
AASDH [31] Aminoadipate-semialdehyde dehydrogenase

EC 6.2.1.- [31]

See also

References

  1. 1 2 3 4 5 6 7 8 9 10 11 12 13 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. 1 2 3 4 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. 1 2 3 4 5 6 "AACS acetoacetyl-CoA synthetase [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2025-02-17.
  4. 1 2 3 4 5 6 7 "ACSF3 acyl-CoA synthetase family member 3 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2025-02-17.
  5. 1 2 3 4 5 6 "ACSS1 acyl-CoA synthetase short chain family member 1 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2025-02-17.
  6. 1 2 3 4 5 6 "ACSS2 acyl-CoA synthetase short chain family member 2 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2025-02-17.
  7. 1 2 3 4 "ACSS3 acyl-CoA synthetase short chain family member 3 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2025-03-08.
  8. 1 2 3 4 "ACSM1 acyl-CoA synthetase medium chain family member 1 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2025-02-17.
  9. 1 2 3 4 "ACSM2A acyl-CoA synthetase medium chain family member 2A [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2025-02-17.
  10. 1 2 3 4 "ACSM2B acyl-CoA synthetase medium chain family member 2B [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2025-02-17.
  11. 1 2 3 4 "ACSM3 acyl-CoA synthetase medium chain family member 3 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2025-02-17.
  12. 1 2 3 4 "ACSM4 acyl-CoA synthetase medium chain family member 4 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2025-03-08.
  13. 1 2 3 "ACSM5 acyl-CoA synthetase medium chain family member 5 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2025-03-08.
  14. 1 2 3 "ACSM6 acyl-CoA synthetase medium chain family member 6 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2025-03-08.
  15. 1 2 3 4 5 6 "ACSL1 acyl-CoA synthetase long chain family member 1 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2025-02-17.
  16. 1 2 3 4 5 6 7 "ACSL3 acyl-CoA synthetase long chain family member 3 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2025-02-17.
  17. 1 2 3 4 "ACSL4 acyl-CoA synthetase long chain family member 4 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2025-02-17.
  18. ↑ "Entry - *300157 - ACYL-CoA SYNTHETASE LONG CHAIN FAMILY, MEMBER 4; ACSL4 - OMIM". omim.org. Retrieved 2024-10-19.
  19. 1 2 3 "ACSL5 acyl-CoA synthetase long chain family member 5 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2025-02-17.
  20. 1 2 3 "ACSL6 acyl-CoA synthetase long chain family member 6 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2025-02-17.
  21. 1 2 3 4 "SLC27A1 solute carrier family 27 member 1 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2025-03-08.
  22. 1 2 3 4 5 6 7 8 9 "SLC27A2 solute carrier family 27 member 2 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2025-02-17.
  23. 1 2 3 "SLC27A3 solute carrier family 27 member 3 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2025-02-17.
  24. 1 2 3 4 "SLC27A4 solute carrier family 27 member 4 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2025-02-17.
  25. 1 2 3 4 5 "SLC27A5 solute carrier family 27 member 5 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2024-10-19.
  26. 1 2 3 "SLC27A6 solute carrier family 27 member 6 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2025-02-17.
  27. 1 2 "ACSBG1 acyl-CoA synthetase bubblegum family member 1 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2025-02-17.
  28. 1 2 3 4 5 "ACSBG2 acyl-CoA synthetase bubblegum family member 2 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2025-02-17.
  29. 1 2 3 "ACSF2 acyl-CoA synthetase family member 2 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2025-02-17.
  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. 1 2 "AASDH aminoadipate-semialdehyde dehydrogenase [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2025-02-17.
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