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.


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


Inherited Metabolic Disorders (IMD) Pathways Rare Diseases


Pathway Ontology

tyrosine metabolic pathway tyrosine degradation pathway tyrosinemia type I pathway tyrosinemia type II pathway alkaptonuria pathway hawkinsinuria pathway tyrosinemia pathway tyrosinemia type III pathway

Disease Ontology

tyrosinemia type I tyrosinemia type III hawkinsinuria alkaptonuria tyrosinemia type II inherited metabolic disorder


Label Type Compact URI 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. Physician’s Guide to the Diagnosis, Treatment, and Follow-Up of Inherited Metabolic Diseases [Internet]. Blau N, Duran M, Gibson KM, Dionisi-Vici C. Springer; 2014. 0 p. Available from: https://books.google.com/books/about/Physician_s_Guide_to_the_Diagnosis_Treat.html?hl=&id=wJRBnwEACAAJ OpenLibrary Worldcat
  2. Mutations in the 4-hydroxyphenylpyruvic acid dioxygenase gene are responsible for tyrosinemia type III and hawkinsinuria. Tomoeda K, Awata H, Matsuura T, Matsuda I, Ploechl E, Milovac T, et al. Mol Genet Metab. 2000 Nov;71(3):506–10. PubMed Europe PMC Scholia
  3. Manifestation of hawkinsinuria in a patient compound heterozygous for hawkinsinuria and tyrosinemia III. Item CB, Mihalek I, Lichtarge O, Jalan A, Vodopiutz J, Muhl A, et al. Mol Genet Metab. 2007 Aug;91(4):379–83. PubMed Europe PMC Scholia
  4. 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. Brownlee JM, Heinz B, Bates J, Moran GR. Biochemistry. 2010 Aug 24;49(33):7218–26. PubMed Europe PMC Scholia
  5. Hypersuccinylacetonaemia and normal liver function in maleylacetoacetate isomerase deficiency. Yang H, Al-Hertani W, Cyr D, Laframboise R, Parizeault G, Wang SP, et al. J Med Genet. 2017 Apr;54(4):241–7. PubMed Europe PMC Scholia
  6. Exploring the therapeutic potential of modern and ancestral phenylalanine/tyrosine ammonia-lyases as supplementary treatment of hereditary tyrosinemia. Hendrikse NM, Holmberg Larsson A, Svensson Gelius S, Kuprin S, Nordling E, Syrén PO. Sci Rep. 2020 Jan 28;10(1):1315. PubMed Europe PMC Scholia