Biosynthesis and regeneration of tetrahydrobiopterin and catabolism of phenylalanine (Homo sapiens)

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<?xml version="1.0" encoding="UTF-8"?> <Pathway xmlns="http://pathvisio.org/GPML/2013a" Name="Biosynthesis and regeneration of tetrahydrobiopterin (BH4) and catabolism of phenylalanine, including diseases" Version="20161102" Organism="Homo sapiens"> <Comment Source="WikiPathways-description"> This pathway shows disorders related to phenylalanine and tetrahydrobiopterin(BH4) metabolism. Disorders resulting from an enzyme defect are highlighted in pink. Pathological metabolites used as specific markers are highlighted in purple. BH4 is a natural cofactor for PAH, tyrosine-3-hydroxylase, tryptophan-5-hydroxylase and nitric oxide synthase (NOS), where the latter two are key enzymes in the biosynthesis of the neurotransmitters dopamine and serotonin. </Comment> <Comment Source="WikiPathways-description">New PW, Chapter 1 of Blau (physicians guide to... inheritant metabolic diseases.</Comment> <Graphics BoardWidth="1559.0267737617141" BoardHeight="1041.161311914324"/> <DataNode TextLabel="DHPR" GraphId="a09c0" Type="Protein"> <Comment>dihydropteridine reductase</Comment> <Graphics CenterX="560.661311914324" CenterY="528.1445783132531" Width="90.0" Height="25.0" ZOrder="32768" FontSize="12" Valign="Middle"/> <Xref Database="Wikidata" ID="Q21145902"/> </DataNode> <DataNode TextLabel="Primapterin" GraphId="a2d68" Type="Metabolite"> <Graphics CenterX="660.0" CenterY="712.3212851405624" Width="90.0" Height="25.0" ZOrder="32768" FontSize="12" Valign="Middle" Color="660066"/> <Xref Database="Wikidata" ID="Q26261687"/> </DataNode> <DataNode TextLabel="DHFR" GraphId="a5763" Type="Protein"> <Comment>dihydrofolate reductase</Comment> <Graphics CenterX="402.0" CenterY="363.0" Width="90.0" Height="25.0" ZOrder="32768" FontSize="12" Valign="Middle"/> <Xref Database="Wikidata" ID="Q417149"/> </DataNode> <DataNode TextLabel="q-BH2" GraphId="b1119" Type="Metabolite"> <Comment>Dihydrobiopterin</Comment> <Graphics CenterX="460.0" CenterY="617.3212851405624" Width="90.0" Height="25.0" ZOrder="32768" FontSize="12" Valign="Middle" Color="0000ff"/> <Xref Database="ChEBI" ID="CHEBI:38797"/> </DataNode> <DataNode TextLabel="BH4" GraphId="b1872" Type="Metabolite"> <Comment>tetrahydropterin</Comment> <Graphics CenterX="559.0" CenterY="404.0" Width="90.0" Height="25.0" ZOrder="32768" FontSize="12" Valign="Middle" Color="0000ff"/> <Xref Database="ChEBI" ID="CHEBI:30436"/> </DataNode> <DataNode TextLabel="PTPS" GraphId="b2bab" Type="GeneProduct"> <Comment>6-pyruvoyl-tetrahydropterin synthase</Comment> <Graphics CenterX="459.0" CenterY="170.54886211512712" Width="90.0" Height="25.0" ZOrder="32768" FontSize="12" Valign="Middle"/> <Xref Database="Wikidata" ID="Q7121042"/> </DataNode> <DataNode TextLabel="GTPCH" GraphId="b30d6" Type="GeneProduct"> <Comment>GTP cyclohydrolase I</Comment> <Graphics CenterX="459.0" CenterY="86.54886211512712" Width="90.0" Height="25.0" ZOrder="32768" FontSize="12" Valign="Middle"/> <Xref Database="Wikidata" ID="Q1487359"/> </DataNode> <DataNode TextLabel="PTP" GraphId="b31bb" Type="Metabolite"> <Comment>6-pyruvoyl tetrahydropterin</Comment> <Graphics CenterX="559.0" CenterY="215.54886211512712" Width="90.0" Height="25.0" ZOrder="32768" FontSize="12" Valign="Middle" Color="0000ff"/> <Xref Database="Wikidata" ID="Q245508"/> </DataNode> <DataNode TextLabel="dihydrofolate reductase deficiency" GraphId="b8a82"> <Comment>DISEASE</Comment> <Graphics CenterX="307.9678714859437" CenterY="466.11244979919684" Width="197.0" Height="25.0" ZOrder="32768" FontSize="12" Valign="Middle" Color="ff00ff"/> <Xref Database="OMIM" ID="126060"/> </DataNode> <DataNode TextLabel="Phe" GraphId="bc2d5" Type="Metabolite"> <Graphics CenterX="1016.3520749665331" CenterY="369.5488621151271" Width="90.0" Height="25.0" ZOrder="32768" FontSize="12" Valign="Middle" Color="0000ff"/> <Xref Database="ChEBI" ID="CHEBI:28044"/> </DataNode> <DataNode TextLabel="GTP cyclohydrolase deficiency" GraphId="bd2bc"> <Comment>DISEASE</Comment> <Graphics CenterX="757.2858099062905" CenterY="56.54886211512714" Width="179.0" Height="25.0" ZOrder="32768" FontSize="12" Valign="Middle" Color="ff00ff"/> <Xref Database="OMIM" ID="233910"/> </DataNode> <DataNode TextLabel="Serotonin" GraphId="bedf2" Type="Metabolite"> <Graphics CenterX="1484.0267737617141" CenterY="911.6278447121822" Width="90.0" Height="25.0" ZOrder="32768" FontSize="12" Valign="Middle" Color="0000ff"/> <Xref Database="ChEBI" ID="CHEBI:1420"/> </DataNode> <DataNode TextLabel="HO-BH4" GraphId="bf2d0" Type="Metabolite"> <Graphics CenterX="660.0" CenterY="617.3212851405624" Width="90.0" Height="25.0" ZOrder="32768" FontSize="12" Valign="Middle" Color="0000ff"/> <Xref Database="" ID=""/> </DataNode> <DataNode TextLabel="SR" GraphId="c323a" Type="GeneProduct"> <Comment>sepiapterin reductase</Comment> <Graphics CenterX="459.0" CenterY="246.54886211512712" Width="90.0" Height="25.0" ZOrder="32768" FontSize="12" Valign="Middle"/> <Xref Database="Wikidata" ID="Q15331000"/> </DataNode> <DataNode TextLabel="5-OH-Trp" GraphId="c505d" Type="Metabolite"> <Graphics CenterX="1276.2543507362789" CenterY="712.3212851405624" Width="90.0" Height="25.0" ZOrder="32768" FontSize="12" Valign="Middle" Color="0000ff"/> <Xref Database="" ID=""/> </DataNode> <DataNode TextLabel="Dopamine" GraphId="c5a50" Type="Metabolite"> <Graphics CenterX="1076.352074966533" CenterY="799.3212851405624" Width="90.0" Height="25.0" ZOrder="32768" FontSize="12" Valign="Middle" Color="0000ff"/> <Xref Database="Wikidata" ID="Q170304"/> </DataNode> <DataNode TextLabel="HVA" GraphId="c7e49" Type="Metabolite"> <Comment>homovanillic acid</Comment> <Graphics CenterX="948.3520749665331" CenterY="799.3212851405624" Width="90.0" Height="25.0" ZOrder="32768" FontSize="12" Valign="Middle" Color="660066"/> <Xref Database="Wikidata" ID="Q903566"/> </DataNode> <DataNode TextLabel="sepiapterin" GraphId="c87ca" Type="Metabolite"> <Graphics CenterX="282.0" CenterY="288.5488621151271" Width="90.0" Height="25.0" ZOrder="32768" FontSize="12" Valign="Middle" Color="660066"/> <Xref Database="Wikidata" ID="Q2271580"/> </DataNode> <DataNode TextLabel="Biopterin" GraphId="cb0ff" Type="Metabolite"> <Graphics CenterX="282.0" CenterY="617.3212851405624" Width="90.0" Height="25.0" ZOrder="32768" FontSize="12" Valign="Middle" Color="660066"/> <Xref Database="Wikidata" ID="Q41793745"/> </DataNode> <DataNode TextLabel="pterin-4a-carbinolamine dehydratasen deficiency" GraphId="cd4cf"> <Comment>DISEASE</Comment> <Graphics CenterX="307.96787148594376" CenterY="704.1499330655957" Width="276.59303882195445" Height="25.0" ZOrder="32768" FontSize="12" Valign="Middle" Color="ff00ff"/> <Xref Database="OMIM" ID="264070"/> </DataNode> <DataNode TextLabel="L-DOPA" GraphId="cf056" Type="Metabolite"> <Graphics CenterX="1016.3520749665331" CenterY="712.3212851405624" Width="90.0" Height="25.0" ZOrder="32768" FontSize="12" Valign="Middle" Color="0000ff"/> <Xref Database="Wikidata" ID="Q300989"/> </DataNode> <DataNode TextLabel="NH2TP" GraphId="cf6a5" Type="Metabolite"> <Graphics CenterX="559.0" CenterY="137.54886211512712" Width="90.0" Height="25.0" ZOrder="32768" FontSize="12" Valign="Middle" Color="0000ff"/> <Xref Database="" ID=""/> </DataNode> <DataNode TextLabel="tyrosine hydroxylase deficiency" GraphId="cf7f4"> <Comment>DISEASE</Comment> <Graphics CenterX="820.204149933066" CenterY="690.763052208835" Width="185.56224899598396" Height="25.0" ZOrder="32768" FontSize="12" Valign="Middle" Color="ff00ff"/> <Xref Database="OMIM" ID="191290"/> </DataNode> <DataNode TextLabel="aromatic l-amino acid decarboxylase deficiency" GraphId="d11b8"> <Comment>DISEASE</Comment> <Graphics CenterX="1290.4953145917002" CenterY="998.661311914324" Width="273.0923694779117" Height="25.0" ZOrder="32768" FontSize="12" Valign="Middle" Color="ff00ff"/> <Xref Database="OMIM" ID="606843"/> </DataNode> <DataNode TextLabel="TH" GraphId="d349a" Type="Protein"> <Comment>tyrosine hydroxylase</Comment> <Graphics CenterX="812.5314591700135" CenterY="634.5635876840697" Width="90.0" Height="25.0" ZOrder="32768" FontSize="12" Valign="Middle"/> <Xref Database="Wikidata" ID="Q420766"/> </DataNode> <DataNode TextLabel="GTP" GraphId="d3b3b" Type="Metabolite"> <Graphics CenterX="559.0" CenterY="49.548862115127164" Width="90.0" Height="25.0" ZOrder="32768" FontSize="12" Valign="Middle" Color="0000ff"/> <Xref Database="ChEBI" ID="CHEBI:37565"/> </DataNode> <DataNode TextLabel="dihydropteridine reductase deficiency" GraphId="d445e"> <Comment>DISEASE</Comment> <Graphics CenterX="307.96787148594376" CenterY="526.1445783132531" Width="210.0" Height="25.0" ZOrder="32768" FontSize="12" Valign="Middle" Color="ff00ff"/> <Xref Database="OMIM" ID="261630"/> </DataNode> <DataNode TextLabel="6-pyruvoyl-tetrahydropterin synthase deficiency" GraphId="d6cbe"> <Comment>DISEASE</Comment> <Graphics CenterX="757.2858099062905" CenterY="170.54886211512712" Width="271.0" Height="25.0" ZOrder="32768" FontSize="12" Valign="Middle" Color="ff00ff"/> <Xref Database="OMIM" ID="261640"/> </DataNode> <DataNode TextLabel="5HIAA" GraphId="d7e33" Type="Metabolite"> <Comment>5-hydroxyindoleacetic acid</Comment> <Graphics CenterX="1105.2717536813925" CenterY="912.9665327978582" Width="90.0" Height="25.0" ZOrder="32768" FontSize="12" Valign="Middle" Color="660066"/> <Xref Database="HMDB" ID="HMDB00763"/> </DataNode> <DataNode TextLabel="oxo-PH4" GraphId="d999d" Type="Metabolite"> <Graphics CenterX="559.0" CenterY="288.5488621151271" Width="90.0" Height="25.0" ZOrder="32768" FontSize="12" Valign="Middle" Color="0000ff"/> <Xref Database="" ID=""/> </DataNode> <DataNode TextLabel="Phenyl-alanine" GraphId="dcc01" Type="Metabolite"> <Graphics CenterX="1017.3520749665331" CenterY="289.5488621151271" Width="102.0" Height="25.0" ZOrder="32768" FontSize="12" Valign="Middle" Color="660066"/> <Xref Database="Wikidata" ID="Q170545"/> </DataNode> <DataNode TextLabel="sepiapterin reductase deficiency" GraphId="e4961"> <Comment>DISEASE</Comment> <Graphics CenterX="757.2858099062905" CenterY="246.54886211512712" Width="194.0" Height="25.0" ZOrder="32768" FontSize="12" Valign="Middle" Color="ff00ff"/> <Xref Database="OMIM" ID="182125"/> </DataNode> <DataNode TextLabel="TPH" GraphId="eb2b3" Type="Protein"> <Comment>tryptophan hydroxylase</Comment> <Graphics CenterX="1361.2543507362789" CenterY="657.3212851405624" Width="90.0" Height="25.0" ZOrder="32768" FontSize="12" Valign="Middle"/> <Xref Database="Enzyme Nomenclature" ID="tryptophan hydroxylase"/> </DataNode> <DataNode TextLabel="Neopterin" GraphId="ec61a" Type="Metabolite"> <Graphics CenterX="754.0" CenterY="137.54886211512712" Width="90.0" Height="25.0" ZOrder="32768" FontSize="12" Valign="Middle" Color="660066"/> <Xref Database="Wikidata" ID="Q908292"/> </DataNode> <DataNode TextLabel="Trp" GraphId="edda5" Type="Metabolite"> <Graphics CenterX="1276.2543507362789" CenterY="617.3212851405624" Width="90.0" Height="25.0" ZOrder="32768" FontSize="12" Valign="Middle" Color="0000ff"/> <Xref Database="Wikidata" ID="Q181003"/> </DataNode> <DataNode TextLabel="PCD" GraphId="ede64" Type="Protein"> <Comment>pterin-4a-carbinolamine dehydratase</Comment> <Graphics CenterX="560.0" CenterY="574.2904953145917" Width="90.0" Height="25.0" ZOrder="32768" FontSize="12" Valign="Middle"/> <Xref Database="Enzyme Nomenclature" ID="4.2.1.96"/> </DataNode> <DataNode TextLabel="7,8-BH2" GraphId="ef7e0" Type="Metabolite"> <Comment>7,8-dihydrobiopterin</Comment> <Graphics CenterX="282.0" CenterY="404.0" Width="90.0" Height="25.0" ZOrder="32768" FontSize="12" Valign="Middle" Color="660066"/> <Xref Database="Wikidata" ID="Q5276421"/> </DataNode> <DataNode TextLabel="Dopa-responsive dystonia" GraphId="f0cf4"> <Comment>DISEASE</Comment> <Graphics CenterX="757.2858099062905" CenterY="102.54886211512712" Width="164.0" Height="25.0" ZOrder="32768" FontSize="12" Valign="Middle" Color="ff00ff"/> <Xref Database="OMIM" ID="600225"/> </DataNode> <DataNode TextLabel="AADC" GraphId="f1930" Type="Protein"> <Comment>aromatic l-amino acid decarboxylase</Comment> <Graphics CenterX="1276.5769745649268" CenterY="810.467202141901" Width="90.0" Height="25.0" ZOrder="32768" FontSize="12" Valign="Middle"/> <Xref Database="" ID=""/> </DataNode> <DataNode TextLabel="CR" GraphId="f3537" Type="Protein"> <Comment>carbonyl reductase</Comment> <Graphics CenterX="361.0" CenterY="324.5488621151271" Width="90.0" Height="25.0" ZOrder="32768" FontSize="12" Valign="Middle"/> <Xref Database="Wikidata" ID="Q1145916"/> </DataNode> <DataNode TextLabel="tyr" GraphId="f39b9" Type="Metabolite"> <Graphics CenterX="1016.3520749665331" CenterY="617.3212851405624" Width="90.0" Height="25.0" ZOrder="32768" FontSize="12" Valign="Middle" Color="0000ff"/> <Xref Database="Wikidata" ID="Q188017"/> </DataNode> <DataNode TextLabel="PAH" GraphId="f3c59" Type="Protein"> <Comment>phenylalanine-4-hydroxylase</Comment> <Graphics CenterX="824.2202141900925" CenterY="389.25836680053544" Width="46.0" Height="25.0" ZOrder="32768" FontSize="12" Valign="Middle"/> <Xref Database="Wikidata" ID="Q420604"/> </DataNode> <DataNode TextLabel="O2" GraphId="f9c2f" Type="Metabolite"> <Graphics CenterX="824.2202141900924" CenterY="460.0160642570281" Width="39.0" Height="25.0" ZOrder="32768" FontSize="12" Valign="Middle" Color="0000ff"/> <Xref Database="ChEBI" ID="CHEBI:15379"/> </DataNode> <DataNode TextLabel="phenylalanine-4-hydroxylase deficiency" GraphId="ffd40"> <Comment>DISEASE</Comment> <Graphics CenterX="828.2362784471205" 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