Tyrosine metabolism and related disorders (WP4506)

Homo sapiens

This pathway shows the tyrosine degradation pathway as presented in Edition 5, Chapter 21 of the book of Blau (ISBN 9783030677268); Ed.4 Ch.2. Disorders resulting from an enzyme defect are highlighted in pink. Red frames mark diagnostically important metabolites.
last edited


Lauren J. Dupuis , Denise Slenter , Egon Willighagen , Irene Hemel , G. Keulen , Friederike Ehrhart , Agustin Gonzalez-Vicente , Eric Weitz , and Finterly Hu

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Homo sapiens


Inborn Errors of Metabolism (IEM) Pathways Rare Diseases


Pathway Ontology: tyrosine metabolic pathway tyrosinemia type I pathway alkaptonuria pathway tyrosinemia type II pathway tyrosine degradation pathway tyrosinemia type III pathway tyrosinemia pathway hawkinsinuria pathway

Disease Ontology: inherited metabolic disorder alkaptonuria tyrosinemia type III tyrosinemia type I tyrosinemia type II hawkinsinuria


Label Type Compact Identifier Comment
Cinnamic acid Metabolite chebi:27386
quinol acetate Metabolite chebi:31128 This compound is annotated with an example for quinol acetate (4-hydroxyphenyl acetate).
BH4 Metabolite chebi:59560 AKA tetrahydrobiopterin
Thiols Metabolite chebi:29256
Phenylalanine Metabolite chebi:17295 AKA L-phenylalanine
Ammonia Metabolite chebi:16134
Hawkinsin Metabolite pubchem.compound:173909 aka 2-cystenyl-1,4-dihydroxycyclohexenylacetate
Homogentisate Metabolite chebi:16169
[CO2] Metabolite chebi:16526
Succinylacetone Metabolite chebi:87897
Maleylacetoacetate Metabolite chebi:17105 AKA 4-Maleylacetoacetate
Fumarate Metabolite chebi:29806
Acetoacetate Metabolite chebi:13705
4-OH-phenylpyruvate Metabolite chebi:36242 aka 4-Hydroxyphenylpyruvate
L-tyrosine Metabolite chebi:58315
NTBC Metabolite chebi:50378 AKA nitisone
4-OH-phenylacetate Metabolite chebi:18101 AKA 4-Hydroxyphenylacetate
Succinylacetoacetate Metabolite chebi:87999
fumarylacetoacetate Metabolite hmdb:HMDB0062563 AKA 4-fumarylacetoacetate
Porphobilinogen Metabolite chebi:17381
4-OH-phenyllactate Metabolite chebi:36659 aka p-Hydroxyphenyllactate
5-Aminolevulinate Metabolite chebi:17549
Coumaric acid Metabolite chebi:36090
BH2 Metabolite chebi:15642 AKA dihydrobiopterin
GSTZ1 GeneProduct uniprot:O43708
PAL Protein eccode: PAL enzymes have side activity towards L-Tyr, mostly from fungi and monocotylic plants.
RgPAL Protein uniprot:Q2VMT1 Species: Rhodotorula glutinis
mutated HPD Protein uniprot:A0A0B4J1R4 HPD gene, with mutation p.Asn241Ser, leading to a change in function in the protein.
Another mutation found to be linked to hawkinsiburia: A heterozygous missense mutation: Ala to Thr change at codon 33 (A33T) [PMID:11073718]
AKA 4-hydroxyphenylpyruvate dioxygenase
HPD Protein uniprot:P32754 HPD gene, without mutation
AKA 4-hydroxyphenylpyruvate dioxygenase
FAH Protein uniprot:P16930 AKA Fumarylacetoacetase
HGD Protein uniprot:Q93099 AKA Homogentisate 1,2-dioxygenase
TAT Protein uniprot:P17735 aka Tyrosine aminotransferase
TAL Protein eccode: PAL enzymes have side activity towards L-Tyr, mostly from fungi and monocotylic plants.
TcTAL Protein uniprot:U5TV35 Species: Trichosporon cutaneum


  1. Blau N, Duran M, Gibson KM, Dionisi-Vici C. Physician’s Guide to the Diagnosis, Treatment, and Follow-Up of Inherited Metabolic Diseases [Internet]. Springer; 2014. 867 p. Available from: https://books.google.com/books/about/Physician_s_Guide_to_the_Diagnosis_Treat.html?hl=&id=wJRBnwEACAAJ OpenLibrary Worldcat
  2. Tomoeda K, Awata H, Matsuura T, Matsuda I, Ploechl E, Milovac T, et al. Mutations in the 4-hydroxyphenylpyruvic acid dioxygenase gene are responsible for tyrosinemia type III and hawkinsinuria. Mol Genet Metab. 2000 Nov;71(3):506–10. PubMed Europe PMC Scholia
  3. Item CB, Mihalek I, Lichtarge O, Jalan A, Vodopiutz J, Muhl A, et al. Manifestation of hawkinsinuria in a patient compound heterozygous for hawkinsinuria and tyrosinemia III. Mol Genet Metab. 2007 Aug;91(4):379–83. PubMed Europe PMC Scholia
  4. Brownlee JM, Heinz B, Bates J, Moran GR. Product analysis and inhibition studies of a causative Asn to Ser variant of 4-hydroxyphenylpyruvate dioxygenase suggest a simple route to the treatment of Hawkinsinuria. Biochemistry. 2010 Aug 24;49(33):7218–26. PubMed Europe PMC Scholia
  5. Yang H, Al-Hertani W, Cyr D, Laframboise R, Parizeault G, Wang SP, et al. Hypersuccinylacetonaemia and normal liver function in maleylacetoacetate isomerase deficiency. J Med Genet. 2017 Apr;54(4):241–7. PubMed Europe PMC Scholia
  6. Hendrikse NM, Holmberg Larsson A, Svensson Gelius S, Kuprin S, Nordling E, Syrén P-O. Exploring the therapeutic potential of modern and ancestral phenylalanine/tyrosine ammonia-lyases as supplementary treatment of hereditary tyrosinemia. Sci Rep. 2020 Jan 28;10(1):1315. PubMed Europe PMC Scholia