Long-chain-fatty-acid—CoA ligase

The fatty acid -CoA ligase ( ACSL ) are enzymes that combine long-chain fatty acids with coenzyme A. Acyl-CoA to. Thus, the fatty acid is prepared either for the installation and storage in triacylglycerols or for degradation via beta - oxidation. The reaction is therefore essential in fat metabolism of eukaryotes.

In humans, so far eight ligases with ACSL - known function that are active in different tissue types and partially also act as transport proteins for fatty acids.

Members

The following five paralogous ligases are single pass type III membrane proteins localized to the outside of several cell organelles. The enzymes require magnesium ions as a cofactor and have a size of about 680-720 amino acids.

  • ACS1 ( UniProt P33121 ) preferred palmitate, oleate, linoleate. Expressed in early stages of erythrocyte development, and in the liver, heart, skeletal muscles, kidneys.
  • ACS3 ( UniProt O95573 ) preferred myristate, laurate, arachidonate, eicosapentaenoate.
  • ACS4 ( UniProt O60488 ) preferred arachidonate eicosapentaenoate. Mutations may be associated with hereditary mental retardation ( MRX63, AMME complex).
  • ACS5 ( UniProt Q9ULC5 ) has broad specificity with preference for unsaturated C16 - C18 fatty acids.
  • ACS6 ( UniProt Q9UKU0 ) broad substrate spectrum.; expressed in reticulocytes, blood stem cells, bone marrow and brain. Mutation associated with forms of leukemia.

In addition, include the following enzymes in the substance group:

  • ACSBG1 ( UniProt Q96GR2 ) has broad-spectrum activity. Mainly localized in the brain ( except pituitary ) and there in the cytosol; to a small extent also in the testes and adrenal glands.
  • ACSBG2 ( UniProt Q5FVE4 ) with a broad spectrum. Exclusively expressed in the testes, both localized in the cytosol and where in the cell membrane. Possible role in spermatogenesis.
  • VLACS ( UniProt O14975 ) preferred C27- bile acids, but can also handle long-chain and branched fatty acids. Acts as a transporter of fatty acids across the membrane of cells in the liver, kidney, placenta, and pancreas.

Catalyzed reaction

ATP CoA -SH AMP PPi ⇒

Fatty acid and coenzyme A are ligated to acyl -CoA.

Triglyceride Transportprotein Myristic acid Hematopoietic stem cell
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