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. This pathway was inspired by Edition 5, Chapter 20 of the book of Blau (ISBN 9783030677268) (Ed.4 Chapter 1).

Authors

Denise Slenter , Egon Willighagen , Irene Hemel , Daniela Digles , Josien Landman , Friederike Ehrhart , and Finterly Hu

Cited In

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Organism

Homo sapiens

Communities

Inborn Errors of Metabolism (IEM) Pathways Rare Diseases

Annotations

Disease Ontology: aromatic L-amino acid decarboxylase deficiency phenylketonuria megaloblastic anemia dystonia 5 sepiapterin reductase deficiency BH4-deficient hyperphenylalaninemia A BH4-deficient hyperphenylalaninemia B

Pathway Ontology: phenylalanine degradation pathway tetrahydrobiopterin metabolic pathway Segawa syndrome pathway phenylketonuria pathway dopa responsive dystonia pathway

Participants

References

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2. Hyland K. Neurochemistry and defects of biogenic amine neurotransmitter metabolism. J Inherit Metab Dis. 1999 Jun;22(4):353–63. PubMed Europe PMC Scholia
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8. Jung-Kc K, Himmelreich N, Prestegård KS, Shi T-JS, Scherer T, Ying M, et al. Phenylalanine hydroxylase variants interact with the co-chaperone DNAJC12. Hum Mutat. 2019 Apr;40(4):483–94. PubMed Europe PMC Scholia
9. Cho H-U, Kim S, Sim J, Yang S, An H, Nam M-H, et al. Redefining differential roles of MAO-A in dopamine degradation and MAO-B in tonic GABA synthesis. Exp Mol Med. 2021 Jul;53(7):1148–58. PubMed Europe PMC Scholia