Fatty acid elongation via elongase pathway of ER

There are two different types of fatty acid elongation takes place in different organisms. These elongation pathways use Coenzyme-A as acyl carrier rather than acyl carrier protein (ACP) as in fatty acid synthesis systems FAS I and FAS II. The first type, mitochondrial fatty acid elongation is the reversal of fatty acid oxidation. This utilises acetyl-CoA as a substrate and extends the chain length of fatty acids with two carbons. This process acts mainly on acyl-CoA shorter than C16. The second process is the elongation pathway of endoplasmic reticulum, which is present in plants, mammals, yeast and other lower eukaryotes. This is a four-step reaction each catalysed by individual enzymes. These enzymes are beta-ketoacyl-CoA synthase, beta-ketoacyl-CoA reductase, beta-hydroxyacyl-CoA dehydratase and trans-2-enoyl-CoA reductase. This pathway mainly acts with acyl-CoA of chain length C16 or larger and important in the generation very long chain fatty acids. This process utilises malonyl-CoA rather than acetyl-CoA for chain elongation. The first enzyme which leads to condensation of malonyl-CoA with acyl-CoA (beta-ketoacyl-CoA synthase) is also called as elongase. There is a single elongase gene in Cryptosporidia as opposed to three different elongase genes in yeast and Coccidia such as Toxoplasma gondii with different substrate specificities. In addition to fatty acid elongation, fatty acid salvage has also been included to this pathway. The fatty acids salvaged from host with the action of acyl-CoA binding proteins (ACBP) can be converted to triacylglycerides with the action of ER-localised enzymes diacylglycerol O-acyltransferase (DGAT) and can be stored in lipid bodies.

 

Enzyme EC Number Gene id
Long chain beta-keto reductase 1.1.1.330 CMU_001110
Long chain trans-2,3-enoyl-CoA reductase 1.3.1.93 CMU_009160
Elongase 2.3.1.199 CMU_042000
Diacylglycerol O-acyltransferase 2.3.1.20 CMU_009280
Diacylglycerol O-acyltransferase 2.3.1.20 CMU_027950
Fatty-acyl-CoA thioesterase I 3.1.2.2 Missing in annotation
Long chain 3-hydroxy acyl-CoA dehydratase 4.2.1.134 CMU_001380
Long-chain-fatty-acid-CoA-ligase 6.2.1.3 CMU_015960
Long-chain-fatty-acid-CoA-ligase 6.2.1.3 CMU_018550
Long-chain-fatty-acid-CoA-ligase 6.2.1.3 CMU_038070
Cytosolic acetyl-CoA carboxylase (ACCase2) 6.3.4.14; 6.4.1.2 CMU_005960
Acyl-CoA binding protein none CMU_035870

 

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Sources and fates of metabolites

 

Substrate Source pathways Product Fate pathways
Fatty acid (upto C16) Host Long-chain Fatty acid Phosphatidylethanolamine and phosphatidylserine metabolism
Acetyl-CoA Tricarboxylic acid (TCA) cycle, Pyruvate metabolism Acyl-CoA GPI anchor biosynthesis, Sphingomyelin and ceramide metabolism
Diacylglycerol Phosphatidylethanolamine and phosphatidylserine metabolism, Inositol phosphate metabolism Triacylglycerol Recycling of phospholipids, Storage in lipid bodies
CoA CoA biosynthesis