Reaction: Succinate <=> Fumarate (with FAD redox reaction on enzyme)
- in pathway: Citric acid cycle (TCA cycle)
The succinate dehydrogenase complex (SDH), associated with the inner mitochondrial membrane, catalyzes the dehydrogenation of succinate to fumarate, reducing the FAD cofactor bound to the enzyme. This redox potential is then used in the electron transfer chain to drive a proton motive force to generate ATP.
The endogenous metabolite itaconate has been shown to bind and inhibit SDH, leading to an accumulation of succinate. Elevated succinate levels modulate immune, hypoxic and metabolic reprogramming pathways, including during oncogenesis (Booth et al, 1952; Dervertanian et al, 1964; Cordes et al, 2016; Lampropoulou et al, 2016). Studies examining the impact of elevated citric acid cycle intermediates such as succinate and fumarate led to the recognition of the role of metabolites in driving cancer progression ('oncometabolites') (Selak et al, 2005; Pollard et al, 2005; Koivunen et al, 2007; reviewed in Hayashi et al, 2018).
The endogenous metabolite itaconate has been shown to bind and inhibit SDH, leading to an accumulation of succinate. Elevated succinate levels modulate immune, hypoxic and metabolic reprogramming pathways, including during oncogenesis (Booth et al, 1952; Dervertanian et al, 1964; Cordes et al, 2016; Lampropoulou et al, 2016). Studies examining the impact of elevated citric acid cycle intermediates such as succinate and fumarate led to the recognition of the role of metabolites in driving cancer progression ('oncometabolites') (Selak et al, 2005; Pollard et al, 2005; Koivunen et al, 2007; reviewed in Hayashi et al, 2018).
Reaction - small molecule participants:
FUMA [mitochondrial matrix]
SUCCA [mitochondrial matrix]
Reactome.org reaction link: R-HSA-70994
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Reaction input - small molecules:
succinate(2-)
Reaction output - small molecules:
fumaric acid
Reactome.org link: R-HSA-70994