48887Pathway1030

Authored: Gopinathrao, G, 2003-03-10 00:00:00, Very long-chain fatty acyl-CoA molecules are synthesized from palmitic acid (C16) or other fatty acids that are synthesized de novo or obtained from the diet. Before they can be elongated, these fatty acids are activated by conversion to fatty acyl-CoAs in reactions catalyzed by the five members of the ACSL (acyl-CoA synthetase long-chain) enzyme family. Elongation proceeds by a four-step reaction sequence parallel to that responsible for the synthesis of palmitate (C16) from acetyl-CoA and malonyl-CoA: a molecule of malonyl-CoA condenses with the long chain fatty acyl-CoA forming a 3-oxoacyl-CoA containing two more carbon atoms than the starting long chain fatty acyl-CoA and CO2. This reaction is catalyzed by one of the seven members of the ELOVL (Elongation of very long chain fatty acids protein) enzyme family. The 3-oxoacyl-CoA is reduced to a 3-hydroxyacyl-CoA by HSD17B12 (hydroxysteroid (17-beta) dehydrogenase 12), 3-hydroxyacyl-CoA is dehydrated to a trans-2,3-enoyl-CoA, and the trans-2,3-enoyl-CoA is reduced to a fatty acid two carbon atoms longer than the input one by TECR (trans-2,3-enoyl-CoA reductase) enzyme. All of these enzyme activities are associated with separate polypeptides associated with the endoplasmic reticulum membrane, unlike the multifunctional and cytosolic FAS complex responsible for synthesis of palmitic acid (Jakobsson ea 2006; Nugteren 1965).<p>The specific reactions annotated here mediate the synthesis of stearoyl-CoA (3-hydroxyoctadecanoyl-CoA) from palmitate, as well as the activation and condensation with malonyl-CoA of arachidonic acid, a 20-carbon unsaturated fatty acid that plays a central role in the synthesis of prostaglandins and related hormones. Human cells contain a wide range of very long chain fatty acids, and the enzymes involved in these reactions are believed to have broader substrate specificities than are shown in these annotations, but few direct experimental data are available to support more extensive annotations.

http://www.reactome.org/biopax/48887Provenance1, urn:biopax:Provenance:reactome_hm_41

Conversion of palmitic acid to very long chain fatty acyl-CoAs

http://www.reactome.org/biopax/48887BiochemicalReaction4172, http://www.reactome.org/biopax/48887BiochemicalReaction4173, http://www.reactome.org/biopax/48887BiochemicalReaction4174, http://www.reactome.org/biopax/48887BiochemicalReaction4175, http://www.reactome.org/biopax/48887BiochemicalReaction4176, http://www.reactome.org/biopax/48887BiochemicalReaction4177, http://www.reactome.org/biopax/48887BiochemicalReaction4178, http://www.reactome.org/biopax/48887BiochemicalReaction4179, http://www.reactome.org/biopax/48887BiochemicalReaction4180, http://www.reactome.org/biopax/48887BiochemicalReaction4181, http://www.reactome.org/biopax/48887BiochemicalReaction4182, http://www.reactome.org/biopax/48887BiochemicalReaction4183, http://www.reactome.org/biopax/48887BiochemicalReaction4184, http://www.reactome.org/biopax/48887BiochemicalReaction4185, http://www.reactome.org/biopax/48887BiochemicalReaction4186