Tyrosine metabolism and related disorders (Homo sapiens)

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ArcPathVisio Brace Ellipse EndoplasmicReticulum GolgiApparatus HexagonPathVisio MimDegradation Mitochondria Octagon PentagonPathVisio Rectangle RoundedRectangle SarcoplasmicReticulum TriangleEquilateralEast TrianglePathVisio none Tyrosinaemia Type IIHawkinsinuriaTyrosinaemia Type ITyrosinaemia Type IIIPALCinnamic acidquinol acetateBH4ThiolsGSTZ1PhenylalanineAmmoniaHawkinsinRgPALHomogentisate[CO2]mutated HPDSuccinylacetoneHPDMaleylacetoacetateFAHFumarateAcetoacetateHGD4-OH-phenylpyruvateL-tyrosineNTBCTAT4-OH-phenylacetateSuccinylacetoacetatefumarylacetoacetatePorphobilinogen4-OH-phenyllactate5-AminolevulinateAlkaptonuriaDiseaseCatalysisPathwayStimulationProteinMetaboliteConversionConnection to diseaseLegendMaleylacetoacetateisomerase decifiencyCoumaric acidProduct ofpotentialtreatmentBH2TALTcTALName: Tyrosine metabolism and related disordersOrganism: Homo sapiens


Description

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.

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Quality Tags

Image:Curated.pngApproved version
Image:Wplogo_31.pngCommunity: Rare Diseases
Image:Wplogo_31.pngCommunity: Inborn Errors of Metabolism (IEM)
Image:Featured.pngFeatured version

Ontology Terms

 

Bibliography

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  1. Blau, Nenad, Duran, Marinus, Gibson, K. Michael, Dionisi-Vici, Carlo; ''Physician's Guide to the Diagnosis, Treatment, and Follow-Up of Inherited Metabolic Diseases''; , 2014
  2. 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 PubMed Europe PMC Scholia
  3. Hao Yang, Walla Al-Hertani, Denis Cyr, Rachel Laframboise, Guy Parizeault, Shu Pei Wang, Francis Rossignol, Marie-Thérèse Berthier, Yves Giguère, Paula J Waters, Grant A Mitchell, Québec NTBC Study Group; ''Hypersuccinylacetonaemia and normal liver function in maleylacetoacetate isomerase deficiency''; J Med Genet ., 2017 PubMed Europe PMC Scholia
  4. Item CB, Mihalek I, Lichtarge O, Jalan A, Vodopiutz J, Muhl A, Bodamer OA; ''Manifestation of hawkinsinuria in a patient compound heterozygous for hawkinsinuria and tyrosinemia III.''; Mol Genet Metab, 2007 PubMed Europe PMC Scholia
  5. Natalie M Hendrikse, Albin Holmberg Larsson, Stefan Svensson Gelius, Sergei Kuprin, Erik Nordling, Per-Olof Syrén; ''Exploring the therapeutic potential of modern and ancestral phenylalanine/tyrosine ammonia-lyases as supplementary treatment of hereditary tyrosinemia''; Sci Rep . , 2020 PubMed Europe PMC Scholia
  6. K Tomoeda, H Awata, T Matsuura, I Matsuda, E Ploechl, T Milovac, A Boneh, C R Scott, D M Danks, F Endo; ''Mutations in the 4-hydroxyphenylpyruvic acid dioxygenase gene are responsible for tyrosinemia type III and hawkinsinuria ''; Mol Genet Metab ., 2000 PubMed Europe PMC Scholia

History

View all...
CompareRevisionActionTimeUserComment
128203
Approved
RARE
Featured
view01:58, 29 January 2024EweitzSoften disease color
123552
IEM
view13:52, 3 August 2022DeSlUpdate Swissprot to Trembl for linkouts
123551view13:51, 3 August 2022DeSlOntology Term : 'hawkinsinuria pathway' added !
123550view13:51, 3 August 2022DeSlOntology Term : 'hawkinsinuria' added !
123549view13:50, 3 August 2022DeSlModified title
123548view13:15, 3 August 2022DeSlLayout changes
123546view13:13, 3 August 2022DeSlAdded new disorder from Edition 5, more details on potential treatment for TT1 (PAL/TAL).
123545view12:24, 3 August 2022DeSlAdded additional variant info on HPD in comments
123544view12:19, 3 August 2022DeSlAddeds ne wlit. ref for HPD gene
123543view12:15, 3 August 2022DeSlAdded approved UniProt ID for 4-hydroxyphenylpyruvate dioxygenase (HPD) without mutation
120405view09:18, 30 November 2021Fehrhartboxed pathway node
119315view13:19, 23 June 2021FinterlyAdded ISBN for book citation
117186view10:20, 18 May 2021EweitzModified title
114404view16:21, 9 January 2021DeSlOntology Term : 'tyrosinemia pathway' added !
114403view16:21, 9 January 2021DeSlOntology Term : 'tyrosinemia type II pathway' added !
114402view16:21, 9 January 2021DeSlOntology Term : 'tyrosinemia type II' added !
114401view16:20, 9 January 2021DeSlFixed typo for Type II.
114400view16:19, 9 January 2021DeSlOntology Term : 'tyrosinemia type III pathway' added !
114399view16:18, 9 January 2021DeSlOntology Term : 'tyrosinemia type III' added !
114398view16:18, 9 January 2021DeSlOntology Term : 'tyrosinemia type I pathway' added !
114397view16:18, 9 January 2021DeSlOntology Term : 'tyrosinemia type I' added !
114396view16:17, 9 January 2021DeSlOntology Term : 'PW:0000013' removed !
114395view16:17, 9 January 2021DeSlAdded biomarker vis. to legend.
114394view16:14, 9 January 2021DeSlAdded legend.
108293view17:08, 4 December 2019AgustinGVfix width and realign Succinylacetone
108292view17:07, 4 December 2019AgustinGV
108076view11:46, 28 November 2019FehrhartOntology Term : 'disease pathway' added !
106201view12:09, 16 August 2019MaintBotHMDB identifier normalization
104393view13:59, 23 May 2019GMKeulenAdded Rhea identifiers and CheBi identifiers
104019view17:35, 25 April 2019IreneHemelModified description
102787view13:24, 24 January 2019EgonwReplaced secondary ChEBI IDs with primary IDs.
102783view10:23, 24 January 2019DeSlOntology Term : 'alkaptonuria pathway' added !
102782view10:23, 24 January 2019DeSlOntology Term : 'alkaptonuria' added !
102781view10:22, 24 January 2019DeSlCreated unique ref for Pubmed 20677779
102780view10:18, 24 January 2019DeSlAdded lit. ref for reaction to Hawkinsin.
102779view10:04, 24 January 2019DeSlAdded side reaction to Hawkinsin.
102777view09:25, 24 January 2019DeSlChanged layout, added last disease, converted lines to disease node to graphical lines.
102759view12:50, 23 January 2019L DupuisModified description
102758view12:47, 23 January 2019L DupuisFramed diagnostically important metabolites
102757view12:42, 23 January 2019L DupuisAdded reference
102756view12:36, 23 January 2019L DupuisLinked omim ids to the disorders
102755view12:24, 23 January 2019L DupuisConverted interaction lines to graphical interface lines to indicate a point where pathology could occur
102754view11:56, 23 January 2019L DupuisConnected unconnected lines
102753view10:06, 23 January 2019L DupuisOntology Term : 'inherited metabolic disorder' added !
102752view10:04, 23 January 2019L DupuisOntology Term : 'tyrosine metabolic pathway' added !
102751view10:03, 23 January 2019L DupuisOntology Term : 'tyrosine degradation pathway' added !
102750view09:58, 23 January 2019L DupuisNew pathway

External references

DataNodes

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Name  ↓Type  ↓Database reference  ↓Comment  ↓
4-OH-phenylacetateMetaboliteCHEBI:18101 (ChEBI) AKA 4-Hydroxyphenylacetate
4-OH-phenyllactateMetaboliteCHEBI:36659 (ChEBI) aka p-Hydroxyphenyllactate
4-OH-phenylpyruvateMetaboliteCHEBI:36242 (ChEBI) aka 4-Hydroxyphenylpyruvate
5-AminolevulinateMetaboliteCHEBI:17549 (ChEBI)
AcetoacetateMetaboliteCHEBI:13705 (ChEBI)
AmmoniaMetaboliteCHEBI:16134 (ChEBI)
BH2MetaboliteCHEBI:15642 (ChEBI) AKA dihydrobiopterin
BH4MetaboliteCHEBI:59560 (ChEBI) AKA tetrahydrobiopterin
Cinnamic acidMetaboliteCHEBI:27386 (ChEBI)
Coumaric acidMetaboliteCHEBI:36090 (ChEBI)
FAHProteinP16930 (Uniprot-TrEMBL) AKA Fumarylacetoacetase
FumarateMetaboliteCHEBI:29806 (ChEBI)
GSTZ1GeneProductO43708 (Uniprot-TrEMBL)
HGDProteinQ93099 (Uniprot-TrEMBL) AKA Homogentisate 1,2-dioxygenase
HPDProteinP32754 (Uniprot-TrEMBL)
  • HPD gene, without mutation
  • AKA 4-hydroxyphenylpyruvate dioxygenase
HawkinsinMetabolite173909 (PubChem-compound) aka 2-cystenyl-1,4-dihydroxycyclohexenylacetate
HomogentisateMetaboliteCHEBI:16169 (ChEBI)
L-tyrosineMetaboliteCHEBI:58315 (ChEBI)
MaleylacetoacetateMetaboliteCHEBI:17105 (ChEBI) AKA 4-Maleylacetoacetate
NTBCMetaboliteCHEBI:50378 (ChEBI) AKA nitisone
PALProtein4.3.1.25 (Enzyme Nomenclature) PAL enzymes have side activity towards L-Tyr, mostly from fungi and monocotylic plants.
PhenylalanineMetaboliteCHEBI:17295 (ChEBI) AKA L-phenylalanine
PorphobilinogenMetaboliteCHEBI:17381 (ChEBI)
RgPALProteinQ2VMT1 (Uniprot-TrEMBL) Species: Rhodotorula glutinis
SuccinylacetoacetateMetaboliteCHEBI:87999 (ChEBI)
SuccinylacetoneMetaboliteCHEBI:87897 (ChEBI)
TALProtein4.3.1.25 (Enzyme Nomenclature) PAL enzymes have side activity towards L-Tyr, mostly from fungi and monocotylic plants.
TATProteinP17735 (Uniprot-TrEMBL) aka Tyrosine aminotransferase
TcTALProteinU5TV35 (Uniprot-TrEMBL) Species: Trichosporon cutaneum
ThiolsMetaboliteCHEBI:29256 (ChEBI)
[CO2]MetaboliteCHEBI:16526 (ChEBI)
fumarylacetoacetateMetaboliteHMDB0062563 (HMDB) AKA 4-fumarylacetoacetate
mutated HPDProteinA0A0B4J1R4 (Uniprot-TrEMBL)
  • 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
quinol acetateMetaboliteCHEBI:31128 (ChEBI) This compound is annotated with an example for quinol acetate (4-hydroxyphenyl acetate).

Annotated Interactions

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Source  ↓Target  ↓Type  ↓Database reference  ↓Comment  ↓
4-OH-phenylpyruvateHomogentisatemim-conversion16190 (Rhea)
Ammoniamim-conversion21385 (Rhea)
Ammoniamim-conversion24907 (Rhea)
BH2mim-conversion20274 (Rhea)
BH4mim-conversion20274 (Rhea)
HomogentisateMaleylacetoacetatemim-conversion15450 (Rhea)
L-tyrosine4-OH-phenylpyruvatemim-conversion15094 (Rhea)
L-tyrosineCoumaric acidmim-conversion24907 (Rhea)
PhenylalanineCinnamic acidmim-conversion21385 (Rhea)
PhenylalanineL-tyrosinemim-conversion20274 (Rhea)
fumarylacetoacetatemim-conversion10245 (Rhea)
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