ReviewMolecular neurobiology2021
Insights from Animal Models on the Pathophysiology of Hyperphenylalaninemia: Role of Mitochondrial Dysfunction, Oxidative Stress and Inflammation.
Review in Molecular neurobiology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 53 citations in OpenAlex.
- Early versus late parenteral nutrition in term and late preterm infants: a randomised controlled trial.BMJ paediatrics open · 2024Trial
- Breath Signatures of Antiseizure Medication Response and Tolerability in Adults With Epilepsy.CNS neuroscience & therapeutics · 2026Observational
- Phenylalanine primes renal tubular redox vulnerability and calcium oxalate crystal retention through a PPARδ-CPT1A fatty-acid oxidation axis.Redox biology · 2026Article
- Targeting Mutant Phenylalanine Hydroxylase With Pyrimidine-Triazole Conjugates: A Primary Framework for Candidate Chaperone-Based Strategies in Phenylketonuria.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Age-Dependent Variation in Blood Biopterin Peaks Following Oral Tetrahydrobiopterin Administration in Phenylketonuria.Journal of inherited metabolic disease · 2026Article
- Phenylalanine homeostasis in metabolic disorders: epidemiological trends, pathophysiological mechanisms, and clinical treatment.Frontiers in endocrinology · 2026Review
- Distinct microbial and metabolic shifts characterize acute coronary syndrome and recovery.iMeta · 2025Article
- Plasma phenylalanine is associated with hospital mortality in acute respiratory distress syndrome: a prospective metabolic profiling cohort study.European journal of medical research · 2025Observational
- Amino Acid Metabolite Profiling for Predicting and Understanding the Metabolic Effects of Metabolic and Bariatric Surgery.Journal of metabolic and bariatric surgery · 2025Review
- Metabolomics and Lipidomics Explore Phenotype-Specific Molecular Signatures for Phenylketonuria.International journal of molecular sciences · 2025Article
- Hydroxysafflor Yellow A modulation of metabolite networks and inhibition of JAK2/STAT1 pathway in sepsis.Scientific reports · 2025Article
- Current state of the treatment landscape of phenylketonuria.Orphanet journal of rare diseases · 2025Review
- The relationship between adult phenylketonuria and the cardiovascular system - insights into mechanisms and risks.Orphanet journal of rare diseases · 2025Review
- Genetically predicted amino acids related to neural regulation mediate the association between diabetes mellitus and postherpetic neuralgia: a Mendelian randomization study.Diabetology & metabolic syndrome · 2025Article
- Metabolic Profiling of Brain Tissue and Brain-Derived Extracellular Vesicles in Alzheimer's Disease.Journal of extracellular vesicles · 2025Article
- Article
- L-carnitine protects against oxidative damage and neuroinflammation in cerebral cortex of rats submitted to chronic chemically-induced model of hyperphenylalaninemia.Metabolic brain disease · 2025Article
- Impact of fluoxetine exposure onFrontiers in pharmacology · 2025Article
- Dissecting Causal Relationship Among Immune Cells, Plasma Metabolites and Coronary Atherosclerosis: A Mendelian Randomization Study.ImmunoTargets and therapy · 2025Article
- The Chinese herbal prescription Kang-Gong-Yan alleviates cervicitis by modulating metabolites and gut microbiota.Pharmaceutical biology · 2024Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Phenylketonuria (PKU) is an inborn error of metabolism caused by phenylalanine hydroxylase (PAH) deficiency and characterized by elevated plasma levels of phenylalanine (hyperphenylalaninemia-HPA). In severe cases, PKU patients present with neurological dysfunction and hepatic damage, but the underlying mechanisms are not fully elucidated. Other forms of HPA also characterized by neurological symptoms occur in rare instances due to defects in the metabolism of the PAH cofactor tetrahydrobiopterin. This review aims to gather the knowledge acquired on the phenylalanine-induced toxicity focusing on findings obtained from pre-clinical studies. Mounting evidence obtained from PKU genetic mice, rats submitted to different HPA models, and cell cultures exposed to phenylalanine has shown that high levels of this amino acid impair mitochondrial bioenergetics, provoke changes in oxidative and inflammatory status, and induce apoptosis. Noteworthy, some data demonstrated that phenylalanine-induced oxidative stress occurs specifically in mitochondria. Further studies have shown that the metabolites derived from phenylalanine, namely phenylpyruvate, phenyllactate, and phenylacetate, also disturb oxidative status. Therefore, it may be presumed that mitochondrial damage is one of the most important mechanisms responsible for phenylalanine toxicity. It is expected that the findings reviewed here may contribute to the understanding of PKU and HPA pathophysiology and to the development of novel therapeutic strategies for these disorders.
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