Fatty acid CoA ligases
| Fatty acid CoA ligases | ||
|---|---|---|
| Identifier | ||
| Gene name (s) | ACSBG1 , ACSBG2 , ACLS1 , ACSL3 , ACSL4 , ACSL5 , ACSL6 , SLC27A2 | |
| Enzyme classification | ||
| EC, category | 6.2.1.3 , ligase | |
| Response type | Acid-thiol esterification | |
| Substrate | ATP + long chain carboxylic acid + CoA | |
| Products | AMP + diphosphate + acyl-CoA + H 2 O | |
| Occurrence | ||
| Parent taxon | Eukaryotes | |
The fatty acid-CoA ligases (ACSL) are enzymes that combine long-chain fatty acids with coenzyme A to form acyl-CoA. This prepares the fatty acid either for incorporation and storage in triacylglycerides or for degradation by means of beta oxidation . The reaction is therefore essential in the lipid metabolism of eukaryotes .
So far, eight ligases with ACSL function are known in humans, which are active in different tissue types and which in some cases also act as transport proteins for fatty acids.
Members
The following five paralog ligases are single pass type III membrane proteins, localized on the outside of several cell organelles . The enzymes require magnesium ions as a cofactor and are around 680 to 720 amino acids in size.
- ACS1 ( UniProt P33121 ) prefers palmitate , oleate , linoleate . Expressed in the early stages of erythrocyte development and in the liver , heart , skeletal muscles , kidneys .
- ACS3 ( UniProt O95573 ) prefers myristate , laurate , arachidonate , eicosapentaenoate .
- ACS4 ( UniProt O60488 ) prefers arachidonate , eicosapentaenoate . Mutations possibly associated with hereditary intellectual disability (MRX63, AMME complex).
- ACS5 ( UniProt Q9ULC5 ) has broad specificity with a preference for C16-C18 unsaturated fatty acids.
- ACS6 ( UniProt Q9UKU0 ) broad substrate spectrum .; expressed in reticulocytes , blood stem cells , bone marrow and brain . Mutation associated with forms of leukemia .
The following enzymes also belong to the group of substances:
- ACSBG1 ( UniProt Q96GR2 ) has a broad spectrum of activity. Localized mainly in the brain (except for the pituitary gland ) and there in the cytosol ; to a lesser extent in the testes and adrenal glands .
- ACSBG2 ( UniProt Q5FVE4 ) with a broad spectrum of activity. Expressed exclusively in the testes , localized there both in the cytosol and in the cell membrane. Possible role in spermatogenesis .
- VLACS ( UniProt O14975 ) prefers C27 bile acids, but can also process long-chain and branched fatty acids. Acts as a transporter for fatty acids across the membrane of cells in the liver , kidneys , placenta and pancreas .
Catalyzed reaction
+ ATP + CoA-SH ⇒ 
+ AMP + PP i
Fatty acid and coenzyme A are ligated to form acyl-CoA.
Individual evidence
- ↑ ENZYME entry 6.2.1.3 . enzyme.expasy.org. Retrieved August 1, 2012.
Web links
- reactome.org: Conversion of Long Chain Fatty Acids to Fatty Acyl-CoAs