Plasmodium falciparum enoyl-[acyl-carrier-protein] reductase (PfFabI)

Plasmodium falciparum enoyl-[acyl-carrier-protein] reductase, commonly known as PfFabI, is a key enzyme in the Type II fatty acid synthesis (FAS-II) pathway located within the parasite's apicoplast (UniProt Q8IL05). This enzyme catalyzes the final, rate-limiting step of the fatty acid elongation cycle, specifically the NADH-dependent reduction of trans-2-enoyl-ACP to acyl-ACP (PMID: 12450375). Unlike humans, who utilize a single large multifunctional Type I fatty acid synthase (FAS-I) complex, Plasmodium parasites rely on the discrete enzymes of the FAS-II system, making PfFabI an attractive target for selective antimalarial drug development (PMID: 11514513). Inhibition of PfFabI disrupts the production of essential fatty acids required for the formation of the parasitophorous vacuole membrane and other vital cellular structures during the liver stage of infection (PMID: 12842901). While several inhibitors like triclosan have demonstrated potent in vitro activity, the clinical utility of PfFabI inhibitors is currently being explored to overcome challenges such as metabolic stability and the potential for rapid resistance development (PMID: 19173371). This target is particularly significant because the FAS-II pathway is essential for the parasite's survival during its development in the liver, offering a potential avenue for prophylactic treatment (PMID: 18636094). Furthermore, the structural differences between the parasite's FabI and human fatty acid synthesis machinery provide a high therapeutic index for drug candidates (PMID: 16212399).

Other names

Enoyl-ACP reductaseFabINADH-dependent enoyl-ACP reductaseENREnoyl-[acyl-carrier-protein] reductase [NADH]

Inhibition of the NADH-dependent reduction of the carbon-carbon double bond in enoyl-ACP intermediates, which is the rate-limiting step in the fatty acid elongation cycle of the Plasmodium falciparum apicoplast (PMID: 12450375).