Human Fumarate Hydratase, Mitochondrial, FH ELI

Catalyzes the reversible stereospecific interconversion of fumarate to L-malate (PubMed: 30761759).

Experiments in other species have demonstrated that specific isoforms of this protein act in defined pathways and favor one direction over the other (Probable).

[Isoform Mitochondrial]: Catalyzes the hydration of fumarate to L-malate in the tricarboxylic acid (TCA) cycle to facilitate a transition step in the production of energy in the form of NADH.

[Isoform Cytoplasmic]: Catalyzes the dehydration of L-malate to fumarate (By similarity).

Fumarate metabolism in the cytosol plays a role during urea cycle and arginine metabolism; fumarate being a by-product of the urea cycle and amino-acid catabolism (By similarity).

Also plays a role in DNA repair by promoting non-homologous end-joining (NHEJ) (PubMed: 20231875, PubMed: 26237645).

In response to DNA damage and phosphorylation by PRKDC, translocates to the nucleus and accumulates at DNA double-strand breaks (DSBs): acts by catalyzing formation of fumarate, an inhibitor of KDM2B histone demethylase activity, resulting in enhanced dimethylation of histone H3 'Lys-36' (H3K36me2) (PubMed: 26237645).