HGD: The gene encoding an enzyme called homogentisate 1,2-dioxygenase (also known as homogentisate oxidase). HGD is located on chromosome 3 in region 3q21-q23.
Homogentisate oxidase is active chiefly in the liver and kidneys. It is needed to break down the amino acids phenylalanine and tyrosine. Previous steps convert these two amino acids into a molecule called homogentisic acid. Homogentisate oxidase adds two oxygen atoms to homogentisic acid, converting it to another molecule called maleylacetoacetate. Other enzymes break down maleylacetoacetate into smaller molecules that are later used for energy or to make other products that can be used by the body.
More than 40 mutations in the HGD gene have been identified in people with alkaptonuria. Many of these mutations change single amino acids in the homogentisate oxidase protein. For example, a substitution of the amino acid valine for methionine at position 368 (also written as Met368Val) is the most common HGD mutation in European populations. Mutations in the HGD gene probably inactivate the enzyme by changing its structure. Without active homogentisate oxidase, homogentisic acid builds up in the body. It is deposited in connective tissues such as cartilage and skin, causing them to darken and leading to arthritis. Homogentisic acid is also present in urine, causing the urine to turn black when exposed to air.