ReviewMolecular genetics and metabolism2022
Phenylketonuria oxidative stress and energy dysregulation: Emerging pathophysiological elements provide interventional opportunity.
Review in Molecular genetics and metabolism, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.
- Metabolomic profiling in phenylketonuria: a systematic review of human studies.Metabolomics : Official journal of the Metabolomic Society · 2026Pooled it
- Phenylalanine primes renal tubular redox vulnerability and calcium oxalate crystal retention through a PPARδ-CPT1A fatty-acid oxidation axis.Redox biology · 2026Article
- Article
- Causal effects of gut microbiota and blood metabolites on subtypes of perinatal depression classified based on depressive symptom trajectories: a mendelian randomization study.Nutrition & metabolism · 2026Article
- Concurrent phenylketonuria and immune-mediated central nervous system involvement: a case report highlighting rare co-occurrence.BMC neurology · 2026Article
- Phenylalanine homeostasis in metabolic disorders: epidemiological trends, pathophysiological mechanisms, and clinical treatment.Frontiers in endocrinology · 2026Review
- Review
- Untargeted Metabolomic Study for Urinary Characterization of Adult Patients with Phenylketonuria.International journal of molecular sciences · 2025Article
- Associations of neonatal birth outcomes with amino acids and acylcarnitines: an observational study of over 3.3 million newborns in China.BMC medicine · 2025Observational
- Concentrations of adrenocorticotropic hormone too low to effect cortisol enhance osteogenesis in vitro and in vivo.American journal of physiology. Endocrinology and metabolism · 2025Article
- Metabolomics and Lipidomics Explore Phenotype-Specific Molecular Signatures for Phenylketonuria.International journal of molecular sciences · 2025Article
- Ex Vivo Osteoclastogenesis from Peripheral Blood Mononuclear Cells Is Unchanged in Adults with Phenylketonuria, Regardless of Dietary Compliance.International journal of molecular sciences · 2025Article
- Current state of the treatment landscape of phenylketonuria.Orphanet journal of rare diseases · 2025Review
- Multi-omics driven biomarker discovery and pathological insights into Pseudomonas aeruginosa pneumonia.BMC infectious diseases · 2025Article
- Multi-omics integration reveals Vha68-3 as a testicular aging-specific factor that coordinates spermatid elongation through mitochondrial metabolic homeostasis.Cellular & molecular biology letters · 2025Article
- Genome-wide association study of plasma amino acids and Mendelian randomization for cardiometabolic traits.Scientific reports · 2025Article
- The Multifaceted Role of L-Type Amino Acid Transporter 1 at the Blood-Brain Barrier: Structural Implications and Therapeutic Potential.Molecular neurobiology · 2025Review
- Multimodal Metabolomic Analysis Reveals Novel Metabolic Disturbances in Adults With Early Treated Phenylketonuria.JIMD reports · 2025Article
- MAZ-mediated tumor progression and immune evasion in hormone receptor-positive breast cancer: Targeting tumor microenvironment and PCLAF+ subtype-specific therapy.Translational oncology · 2025Article
- Inborn errors of amino acid metabolism - from underlying pathophysiology to therapeutic advances.Disease models & mechanisms · 2023Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Phenylalanine hydroxylase (PAH) deficient phenylketonuria (PKU) is rightfully considered the paradigm treatable metabolic disease. Dietary substrate restriction (i.e. phenylalanine (Phe) restriction) was applied >60 years ago and remains the primary PKU management means. The traditional model of PKU neuropathophysiology dictates blood Phe over-representation directs asymmetric blood:brain barrier amino acid transport through the LAT1 transporter with subsequent increased cerebral Phe concentration and low concentrations of tyrosine (Tyr), tryptophan (Trp), leucine (Leu), valine (Val), and isoleucine (Ile). Low Tyr and Trp concentrations generate secondary serotonergic and dopaminergic neurotransmitter paucities, widely attributed as drivers of PKU neurologic phenotypes. White matter disease, a central PKU characteristic, is ascribed to Phe-mediated tissue toxicity. Impaired cerebral protein synthesis, by reduced concentrations of non-Phe large neutral amino acids, is another cited pathological mechanism. The PKU amino acid transport model suggests Phe management should be more efficacious than is realized, as even early identified, continuously treated patients that retain therapy compliance into adulthood, demonstrate neurologic disease elements. Reduced cerebral metabolism was an early-recognized element of PKU pathology. Legacy data (late 1960's to mid-1970's) determined the Phe catabolite phenylpyruvate inhibits mitochondrial pyruvate transport. Respirometry of Pah
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.