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Gene Review

Hpd  -  4-hydroxyphenylpyruvate dioxygenase

Rattus norvegicus

Synonyms: 4-hydroxyphenylpyruvic acid oxidase, 4HPPD, F Alloantigen, F protein, HPD, ...
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Disease relevance of Hpd


High impact information on Hpd

  • Both cell lines displayed increased toxicity with higher concentrations of HPD; however, the AY27 cells were more susceptible to the toxic effects of HPD PDT than the RBL-01 cells at the higher HPD doses studied (25 and 50 micrograms/ml) [3].
  • Both cell lines demonstrated fast initial uptake of HPD followed by slower uptake over the time studied [3].
  • The initial morphologic change following HPD PDT was damage to mitochondria [3].
  • They also bear minimal or no Ag-F alloantigen, a peripheral T cell marker, and they express Ia-like products analogous to those of the mouse I-A subregion but not of the I-E/C subregion [5].
  • RESULTS: Vitamin D-binding protein, paraoxonase, cellular retinol-binding protein, malate dehydrogenase, F-protein, and purine nucleoside phosphorylase were identified as empirically confirmed serum markers for hepatic effects in drug-treated rats [6].

Chemical compound and disease context of Hpd


Biological context of Hpd


Anatomical context of Hpd


Associations of Hpd with chemical compounds

  • The soluble, active recombinant enzyme was shown to contain both 4HPPD and alpha-ketoisocaproate dioxygenase (alpha KICD) activity [1].
  • 4-hydroxyphenylpyruvate dioxygenase (HPD) is an important enzyme involved in tyrosine catabolism [2].
  • Even in N rats on a HPD, high PTH levels (67 +/- 8 pg/ml in the N-IPTG-HPD group) were required to maintain normal serum calcitriol levels (69 +/- 4 vs. 56 +/- 6 pg/ml in Nx-IPTG-HPD and Nx-PTHR-HPD groups, respectively; P < 0.05) [4].
  • These results indicate that proteolytic cleavage of the F protein, with a single arginine residue at the cleavage site, occurs extracellularly in the allantoic cavity of chick embryos and in the bronchial lumen of rats [15].
  • CLT (160 micrograms/kg) significantly inhibited HPD (2 mg/kg)-induced increase in dopamine (DA) release from the rat striatum [8].

Other interactions of Hpd

  • The results seen with the solubilized enzyme, with either Lubrol PX or cholate, indicate that the effects of forskolin on the cyclase do not require either G/F protein or calmodulin and the results of our study of brain enzymes support this view [12].

Analytical, diagnostic and therapeutic context of Hpd

  • However, upon truncation of the 14 amino acids at the C-terminus by site-directed mutagenesis, the resulting mutant enzyme (rat F antigen) exhibited complete loss of 4HPPD and alpha KICD activities [1].
  • The mean urinary dopamine excretion for the 4 days of HPD significantly increased to 4.5 +/- 0.5 microgram/day in the group with chronic bilateral renal denervation and 3.7 +/- 0.2 microgram/day in the group with innervated kidneys [16].
  • Moreover, the photosensitization of mitochondria by the tumor-localizing porphyrin dimer/oligomer fraction of 'HPD' was not inhibited by benzodiazepines in cell culture [17].
  • Young male albino rats (120+/-5 g) were kept for 30 d on the following synthetic diets--High Protein Diet (HPD): 59% casein; Low Protein Diet (LPD): 5% casein; High Fat Diet (HFD): 51% fat; and Standard Diet (SD); 19% casein, 11% fat, and 60% sucrose [18].
  • Free-flow micropunctures under acute Pi infusion were made at elevated but similar filtered loads of Pi: LPD, 6.07 +/- 0.29 (n, 32); HPD 5.34 +/- 0.24 (n, 33) micromol/kidney per min [19].


  1. The C-terminal of rat 4-hydroxyphenylpyruvate dioxygenase is indispensable for enzyme activity. Lee, M.H., Zhang, Z.H., MacKinnon, C.H., Baldwin, J.E., Crouch, N.P. FEBS Lett. (1996) [Pubmed]
  2. Tissue distribution, intracellular localization and proteolytic processing of rat 4-hydroxyphenylpyruvate dioxygenase. Neve, S., Aarenstrup, L., Tornehave, D., Rahbek-Nielsen, H., Corydon, T.J., Roepstorff, P., Kristiansen, K. Cell Biol. Int. (2003) [Pubmed]
  3. Cellular effects of hematoporphyrin derivative photodynamic therapy on normal and neoplastic rat bladder cells. Shulok, J.R., Klaunig, J.E., Selman, S.H., Schafer, P.J., Goldblatt, P.J. Am. J. Pathol. (1986) [Pubmed]
  4. Relative effects of PTH and dietary phosphorus on calcitriol production in normal and azotemic rats. Tallon, S., Berdud, I., Hernandez, A., Concepcion, M.T., Almaden, Y., Torres, A., Martin-Malo, A., Felsenfeld, A.J., Aljama, P., Rodriguez, M. Kidney Int. (1996) [Pubmed]
  5. Expression of T cell differentiation antigens and Ia on rat cytotoxic T lymphocytes. Duarte, A.J., Carpenter, C.B., Strom, T.B. J. Immunol. (1982) [Pubmed]
  6. Use of proteomic methods to identify serum biomarkers associated with rat liver toxicity or hypertrophy. Amacher, D.E., Adler, R., Herath, A., Townsend, R.R. Clin. Chem. (2005) [Pubmed]
  7. Inhibition of 4-hydroxyphenylpyruvate dioxygenase by 2-(2-nitro-4-trifluoromethylbenzoyl)-cyclohexane-1,3-dione and 2-(2-chloro-4-methanesulfonylbenzoyl)-cyclohexane-1,3-dione. Ellis, M.K., Whitfield, A.C., Gowans, L.A., Auton, T.R., Provan, W.M., Lock, E.A., Smith, L.L. Toxicol. Appl. Pharmacol. (1995) [Pubmed]
  8. Inhibitory effect of ceruletide on haloperidol-induced catalepsy in rats. Ibii, N., Ikeda, M., Takahara, Y., Eigyo, M., Akiyoshi, T., Matsushita, A. Peptides (1989) [Pubmed]
  9. Penetration of hematoporphyrin derivative into rat brain and intracerebral 9L glioma tissue. Boisvert, D.P., McKean, J.D., Tulip, J., Cummins, J., Cheng, M.K. J. Neurooncol. (1985) [Pubmed]
  10. Effects of an early weaning on phosphate transport maturation in the rat kidney: influence of the phosphate content of the diet. Lelievre-Pegorier, M., Leroy, B., Moreau, E., Herpe-Patsouris, L., Merlet-Benichou, C. Pediatr. Res. (1992) [Pubmed]
  11. The effect of a high phosphorus diet on the parathyroid cell cycle. Canalejo, A., Hernández, A., Almadén, Y., Concepción, M.T., Felsenfeld, A., Torres, A., Rodríguez, M. Nephrol. Dial. Transplant. (1998) [Pubmed]
  12. Activation of adenylate cyclase by forskolin in rat brain and testis. Sano, M., Kitajima, S., Mizutani, A. Arch. Biochem. Biophys. (1983) [Pubmed]
  13. Multicellular spheroids as an in vitro model system for photoradiation therapy in the presence of Hpd. Christensen, T., Moan, J., Sandquist, T., Smedshammer, L. Prog. Clin. Biol. Res. (1984) [Pubmed]
  14. The differential detergent solubilization of adenylate cyclase and polypeptides ADP-ribosylated with cholera toxin suggests an excess of G/F protein relative to adenylate cyclase in rat pancreatic plasma membranes. Svoboda, M., Furnelle, J., Christophe, J. FEBS Lett. (1981) [Pubmed]
  15. Antibody against the carboxyl terminus of the F2 subunit of Sendai virus fusion glycoprotein inhibits proteolytic activation. Tashiro, M., Takeda, M., Tanaka, S., Nishimura, N., Takenaka, M., Kido, H. Virology (1993) [Pubmed]
  16. Effect of increased dietary phosphate intake on dopamine excretion in the presence and absence of the renal nerves. Berndt, T.J., Khraibi, A.A., Thothathri, V., Dousa, T.P., Tyce, G.M., Knox, F.G. Mineral and electrolyte metabolism. (1994) [Pubmed]
  17. Interactions between porphyrins and mitochondrial benzodiazepine receptors. Kessel, D. Cancer Lett. (1988) [Pubmed]
  18. Effect of diet on dichlorovinyl dimethyl phosphate toxicity in rats. Purshottam, T., Kaveeshwar, U. Aviation, space, and environmental medicine. (1979) [Pubmed]
  19. Tubular localization of adaptation to dietary phosphate in rats. Mühlbauer, R.C., Bonjour, J.P., Fleisch, H. Am. J. Physiol. (1977) [Pubmed]
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