Fumarate hydratase is an enzyme that functions in the mitochondrial citric acid cycle, catalyzing the reversible hydration/dehydration reaction in which fumarate is converted to malate.
The human gene encoding fumarate hydratase is located in the chromosome segment 1q42.3 to q43. It consists of ten exons that span over 20 kb of genomic DNA. The transcript is approximately 1.8 kb long and is predicted to encode a 510 amino acid polypeptide. The first exon of FHencodes a signal peptide that directs the protein to the mitochondrion. There the signal peptide is cleaved, and the remaining mature FH protein forms a functional homotetramer in the mitochondrial matrix. Some processed FH is also present in the cytosol, although the function of this cytosolic FH is unclear. In addition to the mitochondrial signal, the processed FH contains other domains such as alpha-helical and lyase domains. The alpha-helixes form a superhelical core for the...