FAHD1 Human

FAHD1 was identified as a novel mitochondrial enzyme with acylpyruvate hydrolase activity . The protein consists of 224 amino acids and has a calculated molecular mass of approximately 24.8 kDa . It contains a FAH domain with conserved residues at the putative catalytic site .

FAHD1 exhibits acylpyruvase activity, which involves the hydrolysis of acetylpyruvate and fumarylpyruvate in vitro . This activity is significant because it identifies FAHD1 as a mitochondrial enzyme with a previously undescribed function. The enzyme’s activity is dependent on conserved amino acids, such as Asp-102 and Arg-106, and requires Mg2+ for maximal activity .

FAHD1 is expressed in various tissues, with the highest expression observed in the liver and kidney . It is also present in several human cell lines, where it localizes to the mitochondria . The enzyme plays a role in the regulation of the tricarboxylic acid (TCA) cycle by acting as an oxaloacetate decarboxylase (ODx) and acylpyruvate hydrolase (ApH) . This dual functionality contributes to the regulation of metabolic flux within the mitochondria.

Research on FAHD1 has led to the identification of potential inhibitors that could modulate its activity . These inhibitors are designed based on the high-resolution X-ray structure of FAHD1 liganded by oxalate . The development of these inhibitors could have implications for understanding and manipulating mitochondrial metabolism.