4hydroxyphenylpyruvate

4-Hydroxyphenylpyruvate is an α-keto acid that appears as an intermediate in the catabolism of the amino acid tyrosine in many organisms, including humans. It is formed by the transamination of tyrosine, in a reaction that transfers the amino group to an acceptor such as α-ketoglutarate, producing glutamate and 4-hydroxyphenylpyruvate.

The next step in the tyrosine degradation pathway is catalyzed by the enzyme 4-hydroxyphenylpyruvate dioxygenase (HPPD), which converts 4-hydroxyphenylpyruvate to homogentisate with incorporation of oxygen and release of carbon dioxide. Homogentisate then proceeds further through the pathway to maleylacetoacetate and eventually to fumarate and acetoacetate, linking tyrosine catabolism to energy metabolism.

Clinical significance in humans is most clearly seen in rare inherited disorders. Deficiency of 4-hydroxyphenylpyruvate dioxygenase causes tyrosinemia type III, characterized by elevated tyrosine and 4-hydroxyphenylpyruvate levels. The clinical presentation is variable and rare, with reports ranging from asymptomatic cases to neurodevelopmental and hepatic involvement.

In addition to its role in normal metabolism, 4-hydroxyphenylpyruvate dioxygenase is a target in medicine and agriculture. In medicine, pharmacological inhibition of HPPD by drugs such as nitisinone is used to treat tyrosinemia type I by blocking the pathway downstream of 4-hydroxyphenylpyruvate. In agriculture, HPPD inhibitors are used as herbicides to disrupt carotenoid synthesis in weeds, producing characteristic plant bleaching.