4-Hydroxyphenylpyruvate dioxygenase (HPPD) (HPPD)

4-Hydroxyphenylpyruvate dioxygenase (HPPD) is a non-heme iron-dependent enzyme that catalyzes the conversion of 4-hydroxyphenylpyruvate to homogentisate, a critical step in the catabolic pathway of tyrosine (UniProt: P32754). In clinical practice, HPPD is the primary therapeutic target for Nitisinone (NTBC), which is used to treat Hereditary Tyrosinemia type I (HT-1) by blocking the pathway upstream of toxic metabolite formation, such as succinylacetone (DrugBank: DB00394). The enzyme is also of significant interest in the treatment of Alkaptonuria, where its inhibition reduces the accumulation of homogentisic acid. Genetic mutations in the HPD gene locus on chromosome 12q24.31 are associated with Tyrosinemia type III and Hawkinsinuria, conditions characterized by impaired tyrosine metabolism (NCBI Gene: 3242). Furthermore, HPPD is a major target for several classes of herbicides, including triketones and pyrazoles, which inhibit the enzyme in plants to disrupt carotenoid biosynthesis and cause bleaching (PubMed: 21434568). While the term 'HPPD gene locus DNA' refers to the genomic sequence, the functional target for small molecule intervention is the HPPD protein.

Other names

HPD4-HPPD4-hydroxyphenylpyruvic acid oxidase4-hydroxyphenylpyruvate 2-monooxygenaseGLOD3

Competitive inhibition of the 4-hydroxyphenylpyruvate dioxygenase enzyme, preventing the conversion of 4-hydroxyphenylpyruvate to homogentisate.