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) of 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 are three different genes which code for elongases in yeast and they have different substrate specificities. The substrate specificities of these enzymes ELO1, ELO2 and ELO3 are shorter saturated fatty acids (C14-C16), longer saturated & monounsaturated fatty acids and monounsaturated & polyunsaturated fatty acids respectively [1]. In contrast, Trypanosoma brucei have two elongase genes which has specificity to shorter fatty acids (ELO1 – C4 to C10 elongation and ELO2 – C10 to C14 elongation) [2].The orthologs of the three yeast elongase genes were identified in Plasmodium falciparum, Toxoplasma gondii and Neospora caninum and they might have similar substrate specificity to that of yeast. Although these genes are present in P. falciparum genome, fatty acid elongation pathway was not reconstructed in MPMP.

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 and cholesterol ester with the action of ER-localised enzymes diacylglycerol O-acyltransferase (DGAT) and sterol O-acyltransferase respectively and can be stored in lipid bodies. There is strong biochemical evidence in P. falciparum and T. gondii to support the acquisition of fatty acids from host [3, 4].

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Sources and fates of metabolites