Cytosolic 4-hydroxyphenylpyruvate dioxygenase (HPD, HPPD) ca...

created [InstanceEdit:179407] Gopinathrao, G, 2006-04-27 13:13:48
dbId 179028
displayName Cytosolic 4-hydroxyphenylpyruvate dioxygenase (HPD, HPPD) ca...
modified [InstanceEdit:9856170] Stephan, Ralf, 2023-12-13
schemaClass Summation
text Cytosolic 4-hydroxyphenylpyruvate dioxygenase (HPD, HPPD) catalyzes the reaction of 3-(4-Hydroxyphenyl)pyruvate (HPP, 4-HPPA) with molecular oxygen to form homogentisate and CO2 (Ruetschi et al. 2000, Lindblad et al. 1970). Unpublished crystallographic data indicate that the enzyme is a homodimer (PDB 3ISQ) utilizing Fe2+ and ascorbate (AscH-). Other structures have Co2+ as a cofactor (5EC3, 8IM2; Dong et al., 2023). However, most studies of the catalytic activity assume Fe2+ is the cofactor (e.g., Liu et al., 2020; Huang et al., 2021). Inhibitors of HPD prevent the toxic effects of accumulated metabolites in tyrosinemia type I. Nitisinone was approved in 2002 by the FDA for this purpose (Lock et al., 1998; McKiernan, 2006). Mutations in HPD can lead to tyrosinemia type III (TYRSN3, MIM:276710; reviewed in Scott, 2006).
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