Fumarase Human
Description
Fumarate Hydratase is purified by proprietary chromatographic techniques.
Product Specs
Product Science Overview
FH is a homotetrameric enzyme, meaning it consists of four identical subunits. Each subunit has a molecular weight of approximately 50 kDa. The enzyme’s active site is located at the interface between subunits, where it binds to fumarate and catalyzes its conversion to L-malate . The enzyme’s structure has been extensively studied using techniques such as X-ray crystallography, revealing detailed insights into its catalytic mechanism and allosteric regulation .
The FH gene is located on chromosome 1 in humans. Mutations in this gene can lead to fumaric aciduria, a rare metabolic disorder characterized by severe neurological and developmental abnormalities . Biallelic germline mutations in FH result in a deficiency of the enzyme, leading to the accumulation of fumarate in the body .
FH deficiency is associated with several diseases, including hereditary leiomyomatosis and renal cell carcinoma (HLRCC). In HLRCC, individuals with a single functional copy of the FH gene are predisposed to developing benign smooth muscle tumors (leiomyomas) and aggressive renal cell carcinomas . The loss of FH activity leads to the accumulation of fumarate, which can act as an oncometabolite, promoting tumorigenesis through various mechanisms, including the inhibition of prolyl hydroxylase enzymes and the stabilization of hypoxia-inducible factors .
Recombinant FH is produced using genetic engineering techniques, where the human FH gene is cloned and expressed in a suitable host organism, such as Escherichia coli. The recombinant enzyme is then purified for use in research and therapeutic applications. Studies on recombinant FH have provided valuable insights into its structure, function, and role in disease .
Research on FH has significant implications for understanding metabolic regulation, cancer biology, and potential therapeutic interventions. For instance, pharmacological inhibition or genetic ablation of FH in macrophages has been shown to affect cellular metabolic states and cytokine balance, highlighting its role in immune cell function and inflammation . Additionally, recombinant FH is used in enzyme replacement therapies for treating FH deficiency and related metabolic disorders .
