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Chemical Compound Review

homogentisate     2-(2,5- dihydroxyphenyl)ethanoate

Synonyms: CHEBI:16169, AC1NUT64, ZINC00388428, c0108, A826718, ...
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Disease relevance of Homogentisic acid


High impact information on Homogentisic acid

  • Homogentisate dioxygenase (HGO) cleaves the aromatic ring during the metabolic degradation of Phe and Tyr [6].
  • Analysis of a class of these mutations demonstrates that loss of homogentisate dioxygenase (leading to alkaptonuria in humans) prevents the effects of a Fah deficiency [2].
  • It is suggested that apoptotic death of renal tubular cells, as induced by administration of homogentisate to Fah-/- Hpd-/- mice, was caused by an intrinsic process, and that renal apoptosis and tubular dysfunctions in tubular cells occurred through different pathways [7].
  • The transformation of 4-hydroxyphenylpyruvate to homogentisate, catalyzed by 4-hydroxyphenylpyruvate dioxygenase (HPPD), plays an important role in degrading aromatic amino acids [8].
  • The reason for this is that in mammalian metabolism the product HG does not feed into other pathways, whereas in plants it is the precursor for the redox active portion of tocopherols and plastoquinones [9].

Chemical compound and disease context of Homogentisic acid


Biological context of Homogentisic acid

  • Mutation screening was performed by single-strand conformation analysis of all homogentisate dioxygenase exons, followed by sequencing of altered conformers [14].
  • A parallel attempt to engineer HppD activity in HmaS was unsuccessful, suggesting that homogentisate synthesis places greater chemical and steric demands on the active site [15].
  • To identify regulators of hmgA, secondary mutagenesis of an S. meliloti strain harboring a hmgA-luxAB reporter gene fusion (N4) was carried out using transposon Tn1721 [16].
  • Gene expression profiles of homogentisate-treated Fah-/- Hpd-/-mice using DNA microarrays [17].
  • The bacterium is unable to grow at the expense of these amino acids as the sole carbon source, although it is able to degrade them to homogentisate, probably by unspecific hydroxylation reactions [18].

Anatomical context of Homogentisic acid


Associations of Homogentisic acid with other chemical compounds


Gene context of Homogentisic acid


Analytical, diagnostic and therapeutic context of Homogentisic acid

  • HPLC assay analysis of each His6-tagged mutant indicated that F337I successfully produced p-hydroxymandelate, along with homogentisate and an unknown compound [31].
  • Gel retardation assays and lacZ translational fusion experiments have shown that hmgR encodes a specific repressor that controls the inducible expression of the divergently transcribed hmgABC catabolic genes, and homogentisate is the inducer molecule [4].


  1. Mutation and polymorphism analysis of the human homogentisate 1, 2-dioxygenase gene in alkaptonuria patients. Beltrán-Valero de Bernabé, D., Granadino, B., Chiarelli, I., Porfirio, B., Mayatepek, E., Aquaron, R., Moore, M.M., Festen, J.J., Sanmartí, R., Peñalva, M.A., de Córdoba, S.R. Am. J. Hum. Genet. (1998) [Pubmed]
  2. Fungal metabolic model for human type I hereditary tyrosinaemia. Fernández-Cañón, J.M., Peñalva, M.A. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  3. Molecular characterization of a gene encoding a homogentisate dioxygenase from Aspergillus nidulans and identification of its human and plant homologues. Fernández-Cañón, J.M., Peñalva, M.A. J. Biol. Chem. (1995) [Pubmed]
  4. The homogentisate pathway: a central catabolic pathway involved in the degradation of L-phenylalanine, L-tyrosine, and 3-hydroxyphenylacetate in Pseudomonas putida. Arias-Barrau, E., Olivera, E.R., Luengo, J.M., Fernández, C., Galán, B., García, J.L., Díaz, E., Miñambres, B. J. Bacteriol. (2004) [Pubmed]
  5. Catabolism of L-tyrosine by the homoprotocatechuate pathway in gram-positive bacteria. Sparnins, V.L., Chapman, P.J. J. Bacteriol. (1976) [Pubmed]
  6. Crystal structure of human homogentisate dioxygenase. Titus, G.P., Mueller, H.A., Burgner, J., Rodríguez De Córdoba, S., Peñalva, M.A., Timm, D.E. Nat. Struct. Biol. (2000) [Pubmed]
  7. A mouse model of renal tubular injury of tyrosinemia type 1: development of de Toni Fanconi syndrome and apoptosis of renal tubular cells in Fah/Hpd double mutant mice. Sun, M.S., Hattori, S., Kubo, S., Awata, H., Matsuda, I., Endo, F. J. Am. Soc. Nephrol. (2000) [Pubmed]
  8. The crystal structures of Zea mays and Arabidopsis 4-hydroxyphenylpyruvate dioxygenase. Fritze, I.M., Linden, L., Freigang, J., Auerbach, G., Huber, R., Steinbacher, S. Plant Physiol. (2004) [Pubmed]
  9. Catalytic, noncatalytic, and inhibitory phenomena: kinetic analysis of (4-hydroxyphenyl)pyruvate dioxygenase from Arabidopsis thaliana. Purpero, V.M., Moran, G.R. Biochemistry (2006) [Pubmed]
  10. L-Phenylalanine and L-tyrosine catabolism by selected Streptomyces species. Pometto, A.L., Crawford, D.L. Appl. Environ. Microbiol. (1985) [Pubmed]
  11. Some kinetic properties of 4-hydroxyphenylpyruvate dioxygenase from Pseudomonas sp. strain P.J. 874. Rundgren, M. Eur. J. Biochem. (1983) [Pubmed]
  12. Degradation of homogentisate by strains of Bacillus and Moraxella. Crawford, R.L. Can. J. Microbiol. (1976) [Pubmed]
  13. On the renal tubular damage in hereditary tyrosinemia and on the formation of succinylacetoacetate and succinylacetone. Fällström, S.P., Lindblad, B., Steen, G. Acta paediatrica Scandinavica. (1981) [Pubmed]
  14. Alkaptonuria, ochronosis, and ochronotic arthropathy. Mannoni, A., Selvi, E., Lorenzini, S., Giorgi, M., Airó, P., Cammelli, D., Andreotti, L., Marcolongo, R., Porfirio, B. Semin. Arthritis Rheum. (2004) [Pubmed]
  15. Conversion of hydroxyphenylpyruvate dioxygenases into hydroxymandelate synthases by directed evolution. O'Hare, H.M., Huang, F., Holding, A., Choroba, O.W., Spencer, J.B. FEBS Lett. (2006) [Pubmed]
  16. The Sinorhizobium meliloti nutrient-deprivation-induced tyrosine degradation gene hmgA is controlled by a novel member of the arsR family of regulatory genes. Milcamps, A., Struffi, P., de Bruijn, F.J. Appl. Environ. Microbiol. (2001) [Pubmed]
  17. Gene expression profiles of homogentisate-treated Fah-/- Hpd-/-mice using DNA microarrays. Tanaka, Y., Nakamura, K., Matsumoto, S., Kimoto, Y., Tanoue, A., Tsujimoto, G., Endo, F. Mol. Genet. Metab. (2006) [Pubmed]
  18. Metabolism of L-phenylalanine and L-tyrosine by the phototrophic bacterium Rhodobacter capsulatus. Sáez, L.P., Castillo, F., Caballero, F.J. Curr. Microbiol. (1999) [Pubmed]
  19. Tocopherol synthesis from homogentisate in Capsicum anuum L. (yellow pepper) chromoplast membranes: evidence for tocopherol cyclase. Arango, Y., Heise, K.P. Biochem. J. (1998) [Pubmed]
  20. Tyrosinaemia type I and apoptosis of hepatocytes and renal tubular cells. Endo, F., Sun, M.S. J. Inherit. Metab. Dis. (2002) [Pubmed]
  21. Concentrations of succinylacetone after homogentisate and tyrosine loading in healthy individuals with low fumarylacetoacetase activity. Kvittingen, E.A., Leonard, J.V., Pettit, B.R., King, G.S. Clin. Chim. Acta (1985) [Pubmed]
  22. Comparative tyrosine degradation in Vibrio cholerae strains. The strain ATCC 14035 as a prokaryotic melanogenic model of homogentisate-releasing cell. Sanchez-Amat, A., Ruzafa, C., Solano, F. Comp. Biochem. Physiol. B, Biochem. Mol. Biol. (1998) [Pubmed]
  23. Inhibition of protein and aminoacyl-tRNA synthesis, and binding and transport sites for aromatic amino acids in the brain in vitro with aromatic acids. Lähdesmäki, P. Int. J. Neurosci. (1984) [Pubmed]
  24. Structural and functional analysis of mutations in alkaptonuria. Rodríguez, J.M., Timm, D.E., Titus, G.P., Beltrán-Valero De Bernabé, D., Criado, O., Mueller, H.A., Rodríguez De Córdoba, S., Peñalva, M.A. Hum. Mol. Genet. (2000) [Pubmed]
  25. Complete rescue of lethal albino c14CoS mice by null mutation of 4-hydroxyphenylpyruvate dioxygenase and induction of apoptosis of hepatocytes in these mice by in vivo retrieval of the tyrosine catabolic pathway. Endo, F., Kubo, S., Awata, H., Kiwaki, K., Katoh, H., Kanegae, Y., Saito, I., Miyazaki, J., Yamamoto, T., Jakobs, C., Hattori, S., Matsuda, I. J. Biol. Chem. (1997) [Pubmed]
  26. Aerobic metabolism of phenylacetic acids in Azoarcus evansii. Mohamed, M.e.l.-.S., Ismail, W., Heider, J., Fuchs, G. Arch. Microbiol. (2002) [Pubmed]
  27. Isolation and properties of gamma-tocopherol methyltransferase in Euglena gracilis. Shigeoka, S., Ishiko, H., Nakano, Y., Mitsunaga, T. Biochim. Biophys. Acta (1992) [Pubmed]
  28. Mode of action of 4-hydroxyphenylpyruvate dioxygenase inhibition by triketone-type inhibitors. Wu, C.S., Huang, J.L., Sun, Y.S., Yang, D.Y. J. Med. Chem. (2002) [Pubmed]
  29. 4-Hydroxyphenylpyruvate dioxygenase. Moran, G.R. Arch. Biochem. Biophys. (2005) [Pubmed]
  30. The determination of flux through phenylalanine hydroxylase and homogentisate oxidase in isolated hepatocytes. Fisher, M.J., Pogson, C.I. Biosci. Rep. (1984) [Pubmed]
  31. Engineering p-hydroxyphenylpyruvate dioxygenase to a p-hydroxymandelate synthase and evidence for the proposed benzene oxide intermediate in homogentisate formation. Gunsior, M., Ravel, J., Challis, G.L., Townsend, C.A. Biochemistry (2004) [Pubmed]
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