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Genetics Home Reference: your guide to understanding genetic conditions     A service of the U.S. National Library of Medicine®

ACS gene family

Reviewed January 2013

What are the ACS genes?

Genes in the ACS gene family provide instructions for making enzymes called acyl-coenzyme A (or acyl-CoA) synthetases and other related enzymes. Acyl-CoA synthetases perform a chemical reaction called a thioesterification that attaches a coenzyme A (CoA) molecule to fatty acids, which are the building blocks used to make fats (lipids). Fatty acids are a major source of energy for the heart and muscles. During periods without food (fasting), fatty acids are also an important energy source for the liver and other tissues. The reaction performed by acyl-CoA synthetases is the first step in the breakdown of fatty acids for energy. Some acyl-CoA synthetases are also involved in the transport of fatty acids into cells, where they are broken down.

Related enzymes produced from genes in the ACS family perform a thioesterification reaction on other types of acids. For example, the enzyme produced from the ACSF3 gene attaches CoA to the organic acids malonic acid and methylmalonic acid, converting them to malonyl-CoA and methylmalonyl-CoA, respectively. These reactions are important for the formation (synthesis), rather than the breakdown, of fatty acids, specifically in cell structures called mitochondria. Mitochondria convert the energy from food into a form that cells can use, and fatty acid synthesis in these structures is thought to be important for their proper functioning. Mutations in the ACSF3 gene cause a condition known as combined malonic and methylmalonic aciduria (CMAMMA), which leads to high levels of malonic acid and methylmalonic acid in the body and causes developmental and neurological problems.

Which genes are included in the ACS gene family?

The HUGO Gene Nomenclature Committee (HGNC) provides an index of gene families ( and their member genes.

Genetics Home Reference summarizes the normal function and health implications of this member of the ACS gene family: ACSF3.

What conditions are related to genes in the ACS gene family?

Genetics Home Reference includes these conditions related to genes in the ACS gene family:

  • combined malonic and methylmalonic aciduria

What glossary definitions help with understanding the ACS gene family?

acids ; aciduria ; breakdown ; cell ; CoA ; coenzyme A ; enzyme ; fasting ; fatty acids ; gene ; mitochondria ; molecule ; neurological ; synthesis ; synthetases

You may find definitions for these and many other terms in the Genetics Home Reference Glossary.


These sources were used to develop the Genetics Home Reference summary for the ACS gene family.

  • Biochemistry (fifth edition, 2002): Fatty Acids Are Linked to Coenzyme A Before They Are Oxidized (
  • Watkins PA, Maiguel D, Jia Z, Pevsner J. Evidence for 26 distinct acyl-coenzyme A synthetase genes in the human genome. J Lipid Res. 2007 Dec;48(12):2736-50. Epub 2007 Aug 30. (
  • Witkowski A, Thweatt J, Smith S. Mammalian ACSF3 protein is a malonyl-CoA synthetase that supplies the chain extender units for mitochondrial fatty acid synthesis. J Biol Chem. 2011 Sep 30;286(39):33729-36. doi: 10.1074/jbc.M111.291591. Epub 2011 Aug 16. (
  • Digel M, Ehehalt R, Stremmel W, Füllekrug J. Acyl-CoA synthetases: fatty acid uptake and metabolic channeling. Mol Cell Biochem. 2009 Jun;326(1-2):23-8. doi: 10.1007/s11010-008-0003-3. Epub 2008 Dec 30. (


The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? ( in the Handbook.

Reviewed: January 2013
Published: February 8, 2016