Fumarate reductase (NADH) (FRD)

Parasite fumarate reductase (FRD) is a critical enzyme in the anaerobic energy metabolism of various helminths, such as Ascaris suum, and certain protozoa. While mammalian mitochondria utilize succinate dehydrogenase (SDH) to oxidize succinate to fumarate during the aerobic citric acid cycle, many parasites operate this complex in reverse to reduce fumarate to succinate. This reaction is typically coupled with the oxidation of rhodoquinone (RQ), a low-potential quinone that is absent in mammalian hosts, making the RQ-FRD system a distinct and selective target for chemotherapy (Kita et al., 2002, PMID: 12160824). By serving as the terminal electron acceptor, FRD enables parasites to maintain energy production and redox balance in the hypoxic environments of the host's digestive tract or tissues (Tielens, 1994, PMID: 7923011). Inhibition of this enzyme system, historically associated with the benzimidazole class of anthelmintics, leads to a failure in ATP synthesis and subsequent parasite paralysis or death (DrugBank, DB00518). Modern research continues to explore FRD as a target for novel anti-parasitic agents to overcome emerging drug resistance in both human and veterinary medicine.

Other names

Rhodoquinone-dependent fumarate reductaseRQ-fumarate reductaseSuccinate dehydrogenase (fumarate reductase)NADH-fumarate reductase systemMitochondrial complex II (parasite)

Inhibition of the rhodoquinone-dependent reduction of fumarate to succinate, which disrupts the parasite's anaerobic electron transport chain and halts ATP production.