Fatty Acid Synthesis in Protozoan Parasites


Three metabolic pathways can be used by protozoan parasites for the de novo synthesis of fatty acids. Parasites employ diverse strategies involving these three pathways, as well as scavenging from the host, to obtain fatty acids required for growth.

Keywords: type I fatty acid synthase; type II fatty acid synthase; fatty acid elongase pathway; apicomplexa; trypanosomatids

Figure 1.

Production of malonyl‐CoA and malonyl‐ACP for fatty acid biosynthesis pathways.

Figure 2.

The four steps of fatty acid elongation. The cycle repeats after the second reduction step (step 4). At this point, the acyl chain has been elongated by two carbons as noted by incrementing n (n=n+1). The letter X represents CoA or ACP depending on the FAS pathway.

Figure 3.

Architecture of type I FAS enzymes. CpFAS1 contains a ligase domain and ACP at the N‐terminus as well as a putative reductase domain at the C‐terminus. Mammalian enzymes contain a C‐terminal thioesterase (TE) domain. Domains of the FAS module are: KS, ketoacyl synthase; AT, acyltransferase; DH, dehydratase; ER, enoyl reductase; KR, ketoacyl reductase and ACP, acyl carrier protein.

Figure 4.

Type II FAS pathway as found in P. falciparum. The initial condensation reaction catalyzed by KASIII can use acetyl‐CoA (n=0) or butyryl‐CoA (n=1) as an acyl primer. The malonyl‐ACP used by both KASII and KASIII is generated as shown in Figure . KAS=β‐ketoacyl‐ACP synthase, KAR=β‐ketoacyl‐ACP reductase, HAD=β‐hydroxyacyl‐ACP dehydratase, ENR=enoyl‐ACP reductase.

Figure 5.

Activity of elongase enzymes. ELO enzymes typically elongate long‐chain fatty acid substrates, whereas the Tr. brucei ELO pathway synthesizes fatty acids de novo from a butyryl primer. ELOs only catalyse the first step of the fatty acid elongation cycle (the three other enzymes needed to complete each cycle are not shown here, see Figure ); PUFA, polyunsaturated fatty acids.



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Further Reading

Coppens I and Vielemeyer O (2005) Insights into unique physiological features of neutral lipids in Apicomplexa: from storage to potential mediation in parasite metabolic activities. International Journal of Parasitology 35: 597–615.

Jakobsson A, Westerberg R and Jacobsson A (2006) Fatty acid elongases in mammals: their regulation and roles in metabolism. Progress in Lipid Research 45: 237–249.

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Vial HJ, Eldin P, Tielens AGM and van Hellemond JJ (2003) Phospholipids in parasitic protozoa. Molecular and Biochemical Parasitology 126: 143–154.

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Allary, Marina, and Prigge, Sean T(Apr 2008) Fatty Acid Synthesis in Protozoan Parasites. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0021018]