ArticleCellular and molecular neurobiology2012
Phenylpyruvic acid decreases glucose-6-phosphate dehydrogenase activity in rat brain.
Article in Cellular and molecular neurobiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 33 citations in OpenAlex.
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- The relationship between adult phenylketonuria and the cardiovascular system - insights into mechanisms and risks.Orphanet journal of rare diseases · 2025Review
- Dysfunction in mitochondrial electron transport chain drives the pathogenesis of pulmonary arterial hypertension: insights from a multi-omics investigation.Respiratory research · 2025Article
- Fecal Microbiota Transplantation from Methionine-Restricted Diet Mouse Donors Improves Alzheimer's Learning and Memory Abilities Through Short-Chain Fatty Acids.Foods (Basel, Switzerland) · 2025Article
- Impact of gut probiotic metabolites on phenylketonuria.Frontiers in cellular and infection microbiology · 2025Review
- Extensive Dysregulation of Phenylalanine Metabolism Is Associated With Stress Hyperphenylalaninemia and 30-Day Death in Critically Ill Patients With Acute Decompensated Heart Failure.Journal of the American Heart Association · 2024Article
- Cardiometabolic Modulation by Semaglutide Contributes to Cardioprotection in Rats with Myocardial Infarction.Drug design, development and therapy · 2024Article
- The Role of Amino Acids in Non-Enzymatic Antioxidant Mechanisms in Cancer: A Review.Metabolites · 2023Review
- A metabolite from commensal Candida albicans enhances the bactericidal activity of macrophages and protects against sepsis.Cellular & molecular immunology · 2023Article
- The Utility of Amino Acid Metabolites in the Diagnosis of Major Depressive Disorder and Correlations with Depression Severity.International journal of molecular sciences · 2023Article
- Identification of metabolic biomarkers for diagnosis of epithelial ovarian cancer using internal extraction electrospray ionization mass spectrometry (iEESI-MS).Cancer biomarkers : section A of Disease markers · 2023Article
- Study on the Effect of Different Iodine Intake on Hippocampal Metabolism in Offspring Rats.Biological trace element research · 2022Article
- Metabolomics and biochemical insights on the regulation of aging-related diabetes by a low-molecular-weight polysaccharide from green microalgaFood chemistry: X · 2022Article
- Phenylketonuria oxidative stress and energy dysregulation: Emerging pathophysiological elements provide interventional opportunity.Molecular genetics and metabolism · 2022Review
- Comparative metabolomics in the PahMolecular genetics and metabolism · 2022Article
- Urinary Aromatic Amino Acid Metabolites Associated With Postoperative Emergence Agitation in Paediatric Patients After General Anaesthesia: Urine Metabolomics Study.Frontiers in pharmacology · 2022Article
- L-carnitine protects DNA oxidative damage induced by phenylalanine and its keto acid derivatives in neural cells: a possible pathomechanism and adjuvant therapy for brain injury in phenylketonuria.Metabolic brain disease · 2021Article
- Insights from Animal Models on the Pathophysiology of Hyperphenylalaninemia: Role of Mitochondrial Dysfunction, Oxidative Stress and Inflammation.Molecular neurobiology · 2021Review
- Engineering Organoids forFrontiers in molecular neuroscience · 2021Review
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Authors and funding
6 authors at 2 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
Phenylketonuria is a recessive autosomal disorder that is caused by a deficiency in the activity of phenylalanine-4-hydroxylase, which converts phenylalanine to tyrosine, leading to the accumulation of phenylalanine and its metabolites phenyllactic acid, phenylacetic acid, and phenylpyruvic acid in the blood and tissues of patients. Phenylketonuria is characterized by severe neurological symptoms, but the mechanisms underlying brain damage have not been clarified. Recent studies have shown the involvement of oxidative stress in the neuropathology of hyperphenylalaninemia. Glucose-6-phosphate dehydrogenase plays an important role in antioxidant defense because it is the main source of reduced nicotinamide adenine dinucleotide phosphate (NADPH), providing a reducing power that is essential in protecting cells against oxidative stress. Therefore, the present study investigated the in vitro effect of phenylalanine (0.5, 1, 2.5, and 5 mM) and its metabolites phenyllactic acid, phenylacetic acid, and phenylpyruvic acid (0.2, 0.6, and 1.2 mM) on the activity of enzymes of the pentose phosphate pathway, which is involved in the oxidative phase in rat brain homogenates. 6-Phosphogluconate dehydrogenase activity was not altered by any of the substances tested. Phenylalanine, phenyllactic acid, and phenylacetic acid had no effect on glucose-6-phosphate dehydrogenase activity. Phenylpyruvic acid significantly reduced glucose-6-phosphate dehydrogenase activity without pre-incubation and after 1 h of pre-incubation with the homogenates. The inhibition of glucose-6-phosphate dehydrogenase activity caused by phenylpyruvic acid could elicit an impairment of NADPH production and might eventually alter the cellular redox status. The role of phenylpyruvic acid in the pathophysiological mechanisms of phenylketonuria remains unknown.
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