Alkaptonuria (AKU), a rare hereditary disorder, was the first disease to be interpreted as an inborn error of metabolism. The deficiency causes homogentisic aciduria, ochronosis, and arthritis. AKU patients are deficient for homogentisate 1,2 dioxygenase (EC: 1.13.11.5), the enzyme that mediates the conversion of homogentisate to maleylacetoacetate; a step in the catabolism of both tyrosine and phenylalanine. Homogentisate + O(2) = 4-maleylacetoacetate.