Homogentisic acid 1,2-dioxygenase

homogentisate 1,2-dioxygenase
3D rendering of Homogentisate Dioxygenase with active site amino acid residues and Iron atom colored. Histidine is the tan color, Glutamate the red color, and Iron is the blue.
Identifiers
EC number	1.13.11.5
CAS number	9029-49-6
Databases
IntEnz	IntEnz view
BRENDA	BRENDA entry
ExPASy	NiceZyme view
KEGG	KEGG entry
MetaCyc	metabolic pathway
PRIAM	profile
PDB structures	RCSB PDB PDBe PDBsum
Gene Ontology	AmiGO / EGO
Search PMC articles PubMed articles NCBI proteins

Homogentisate 1,2-dioxygenase (homogentisic acid oxidase, homogentisicase) is an enzyme which catalyzes the conversion of homogentisate to 4-maleylacetoacetate. Homogentisate 1,2-dioxygenase or HGD is involved in the catabolism of aromatic rings, more specifically in the breakdown of the amino acids tyrosine and phenylalanine. HGD appears in the metabolic pathway of tyrosine and phenylalanine degradation once the molecule homogentisate is produced. Homogentisate reacts with HGD to produce maleylacetoacetate, which then is further used in the metabolic pathway. HGD requires the use of Fe²⁺ and O₂ in order to cleave the aromatic ring of homogentisate.

homogentisate

4-maleylacetoacetate

The active site of Homogentisate 1,2-dioxygenase was determined through the crystal structure, which was captured through the work of Titus et al. Through the crystal structure the active site was found to contain the following residues; His292, His335, His365, His371, and Glu341.

Homogentisate binds in the active site to Glu341, His335, and His371 via the Fe2+ atom. The His292 binds to the hydroxyl group of the aromatic ring. His365 binds to Glu341 via hydrogen bonding to stabilize the amino acid side chains.

Homegentisate 1,2 dioxygenase is involved in a type of metabolic diseases, called alkaptonuria. This disorder is due to the inability of the body to deal with homogentisate, which when oxidized by the body will produce the compound known as the ochronotic pigment, which causes a black color, and has several negative effects. This first of these effects is that the patient’s earwax will begin to turn black or red, depends on the patient’s diet, since the blood becomes oxidized and thus turns black due to excess of the ochronotic pigment. The other effect of the ochronotic pigment is that it can accumulate in the body’s connective tissue leading to degenerative arthritis, as the person grows older. Alkaptonuria has another effect in that it can cause the urine to turn black as well if let to sit for long enough to become oxidized, though is this often a method for testing for the genetic defect. The metabolic disease is autosomal recessive, such that both parents must pass the gene on to their children in order for child to have the defect.