ArticleJournal of inherited metabolic disease2014
Pharmacologic inhibition of L-tyrosine degradation ameliorates cerebral dopamine deficiency in murine phenylketonuria (PKU).
Article in Journal of inherited metabolic disease, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 48 citations in OpenAlex.
- Exploring Subpopulations for Epidemiological Precision Nutrition Research: The Example ofNutrients · 2026Article
- Small Phenolic Metabolites at the Nexus of Nutrient Transport and Energy Metabolism.Molecules (Basel, Switzerland) · 2025Review
- Dissecting Holistic Metabolic Acclimatization ofBiology · 2024Article
- Impact of Nitisinone on the Cerebrospinal Fluid Metabolome of a Murine Model of Alkaptonuria.Metabolites · 2022Article
- Modeling the cognitive effects of diet discontinuation in adults with phenylketonuria (PKU) using pegvaliase therapy in PAH-deficient mice.Molecular genetics and metabolism · 2022Article
- A Review of Sensors and Biosensors Modified with Conducting Polymers and Molecularly Imprinted Polymers Used in Electrochemical Detection of Amino Acids: Phenylalanine, Tyrosine, and Tryptophan.International journal of molecular sciences · 2022Review
- The effect of casein glycomacropeptide versus free synthetic amino acids for early treatment of phenylketonuria in a mice model.PloS one · 2022Article
- Physical Growth of Patients with Hereditary Tyrosinaemia Type I: A Single-Centre Retrospective Study.Nutrients · 2021Article
- Phenylketonuria.Nature reviews. Disease primers · 2021Review
- Development of a porcine model of phenylketonuria with a humanized R408W mutation for gene editing.PloS one · 2021Article
- Metabolic and catecholamine response to sympathetic stimulation in early-treated adult male patients with phenylketonuria.Hormones (Athens, Greece) · 2020Article
- Adeno-Associated Virus and Hematopoietic Stem Cells: The Potential of Adeno-Associated Virus Hematopoietic Stem Cells in Genetic Medicines.Human gene therapy · 2020Review
- Long-Term Outcomes and Practical Considerations in the Pharmacological Management of Tyrosinemia Type 1.Paediatric drugs · 2019Review
- Blood and Brain Biochemistry and Behaviour in NTBC and Dietary Treated Tyrosinemia Type 1 Mice.Nutrients · 2019Article
- Assessing the effect of nitisinone induced hypertyrosinaemia on monoamine neurotransmitters in brain tissue from a murine model of alkaptonuria using mass spectrometry imaging.Metabolomics : Official journal of the Metabolomic Society · 2019Article
- Substrate reduction therapy for inborn errors of metabolism.Emerging topics in life sciences · 2019Article
- Hippocampal metabolism of amino acids by L-amino acid oxidase is involved in fear learning and memory.Scientific reports · 2018Article
- Serum Amino Acid Profiling in Patients with Alkaptonuria Before and After Treatment with Nitisinone.JIMD reports · 2018Article
- Blood phenylalanine reduction corrects CNS dopamine and serotonin deficiencies and partially improves behavioral performance in adult phenylketonuric mice.Molecular genetics and metabolism · 2018Article
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6 authors at 2 institutions in 1 country.
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Abstract
Monoamine neurotransmitter deficiency has been implicated in the etiology of neuropsychiatric symptoms associated with chronic hyperphenylalaninemia in phenylketonuria (PKU). Two proposed explanations for neurotransmitter deficiency in PKU include first, that chronically elevated blood L-phenylalanine (Phe) inhibits the transport of L-tyrosine (Tyr) and L-tryptophan (Trp), the substrates for dopamine and serotonin synthesis respectively, into brain. In the second hypothesis, elevated Phe competitively inhibits brain tyrosine hydroxylase (TH) and tryptophan hydroxylase (TPH) activities, the rate limiting steps in dopamine and serotonin synthesis. Dietary supplementation with large neutral amino acids (LNAA) including Tyr and Trp has been recommended for individuals with chronically elevated blood Phe in an attempt to restore amino acid and monoamine homeostasis in brain. As a potential alternative treatment approach, we demonstrate that pharmacologic inhibition of Tyr degradation through oral administration of nitisinone (NTBC) yielded sustained increases in blood and brain Tyr, decreased blood and brain Phe, and consequently increased dopamine synthesis in a murine model of PKU. Our results suggest that Phe-mediated inhibition of TH activity is the likely mechanism of impaired dopamine synthesis in PKU. Pharmacologic inhibition of Tyr degradation may be a promising adjunct therapy for CNS monoamine neurotransmitter deficiency in hyperphenylalaninemic individuals with PKU.
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