Homogentisate 1,2-dioxygenase (HGD)

Homogentisate 1,2-dioxygenase (HGD) is an iron-dependent enzyme primarily expressed in the liver and kidney that catalyzes a key step in the catabolic pathway of the aromatic amino acids tyrosine and phenylalanine, specifically converting homogentisic acid to maleylacetoacetate[1][2][3][5][6]. Deficiency of HGD, due to genetic mutations, leads to the accumulation of homogentisic acid and causes the rare metabolic disorder alkaptonuria, which manifests with dark urine, ochronotic pigment deposition, and progressive degenerative arthritis and organ involvement[1][2][4]. HGD belongs to the class of dioxygenases and requires Fe^2+^ for catalytic activity[1][3][5]. While no drugs directly target HGD, nitisinone acts upstream in the pathway to reduce homogentisic acid accumulation in patients with alkaptonuria, and chaperone therapies are under investigation to restore or stabilize mutant HGD protein function[3][4].

Other names

AKUHGOHGD_HUMANhomogentisic acid oxidasehomogentisate oxidasehomogentisicase

Enzyme inhibition (for nitisinone: inhibits 4-hydroxyphenylpyruvate dioxygenase, reducing substrate for HGD), Protein stabilization/chaperones (investigational—aimed at rescuing enzyme function)