Homogentisic

Homogentisic acid, also known as homogentisate, is a hydroxyphenylacetic acid that serves as an intermediate in the catabolism of the amino acids tyrosine and phenylalanine. Its commonly cited IUPAC name is 2,5-dihydroxyphenylacetic acid. In humans, it is produced from p-hydroxyphenylpyruvate by the enzyme p-hydroxyphenylpyruvate dioxygenase and is normally further metabolized by homogentisate 1,2-dioxygenase to maleylacetoacetate in the tyrosine degradation pathway.

Clinical significance is most often associated with deficiency of homogentisate 1,2-dioxygenase, which causes alkaptonuria, a rare inherited metabolic disorder. This leads to the accumulation of homogentisic acid in tissues and body fluids. Urine may darken upon standing due to oxidation of the compound. Chronic accumulation can result in ochronosis, pigment deposition in connective tissues such as cartilage and intervertebral discs, and can contribute to early-onset degenerative arthritis and other connective tissue complications.

Diagnosis typically relies on detection of elevated urinary homogentisic acid and may be confirmed by genetic testing. Management focuses on reducing the production and accumulation of homogentisic acid and monitoring for related complications. Dietary restrictions limiting phenylalanine and tyrosine intake have been used in some settings, and pharmacologic reduction of homogentisic acid with nitisinone has shown promise in lowering urinary excretion and potentially slowing ochronosis. Regular clinical follow-up is advised to assess joint, cardiac, and spinal health.