ArticleScientific reports2015
Molecular mechanisms of the non-coenzyme action of thiamin in brain: biochemical, structural and pathway analysis.
Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 127 citations in OpenAlex.
- Benfotiamine and Cognitive Decline in Alzheimer's Disease: Results of a Randomized Placebo-Controlled Phase IIa Clinical Trial.Journal of Alzheimer's disease : JAD · 2020Trial
- Daytime-Dependent Effects of Thiamine on the Thiamine Pool and Pyruvate Dehydrogenase Regulation in the Brain and Heart.International journal of molecular sciences · 2025Article
- Optimal dietary vitamin B1 content enhanced egg production, eggshell thickness, and serum antioxidant status in breeder geese.Animal bioscience · 2025Article
- Neanderthal and Denisovan Glutamate Dehydrogenase 2 Evolution and Clinical Significance.International journal of molecular sciences · 2025Article
- Thiamine, gastrointestinal beriberi and acetylcholine signaling.Frontiers in nutrition · 2025Review
- Small molecule modulation of protein corona for deep plasma proteome profiling.Nature communications · 2024Article
- Deep Plasma Proteome Profiling by Modulating Single Nanoparticle Protein Corona with Small Molecules.bioRxiv : the preprint server for biology · 2024Article
- The effect of psychoactive bacteria, Bifidobacterium longum Rosell®-175 and Lactobacillus rhamnosus JB-1, on brain proteome profiles in mice.Psychopharmacology · 2024Article
- Evolutionary Changes in Primate Glutamate Dehydrogenases 1 and 2 Influence the Protein Regulation by Ligands, Targeting and Posttranslational Modifications.International journal of molecular sciences · 2024Review
- The Impacts of Slc19a3 Deletion and Intestinal SLC19A3 Insertion on Thiamine Distribution and Brain Metabolism in the Mouse.Metabolites · 2023Article
- Synthetic Thioesters of Thiamine: Promising Tools for Slowing Progression of Neurodegenerative Diseases.International journal of molecular sciences · 2023Review
- Thiourea derivatives containing 4-arylthiazoles and d-glucose moiety: design, synthesis, antimicrobial activity evaluation, and molecular docking/dynamics simulations.RSC medicinal chemistry · 2023Article
- - Invited Review - Postmortem skeletal muscle metabolism of farm animals approached with metabolomics.Animal bioscience · 2023Article
- The Rationale for Vitamin, Mineral, and Cofactor Treatment in the Precision Medical Care of Autism Spectrum Disorder.Journal of personalized medicine · 2023Review
- The differential plasma and ruminal metabolic pathways and ruminal bacterial taxa associated with divergent residual body weight gain phenotype in crossbred beef steers.Translational animal science · 2023Article
- A Clinician's View of Wernicke-Korsakoff Syndrome.Journal of clinical medicine · 2022Review
- The Brain Protein Acylation System Responds to Seizures in the Rat Model of PTZ-Induced Epilepsy.International journal of molecular sciences · 2022Article
- Structural Basis for the Binding of Allosteric Activators Leucine and ADP to Mammalian Glutamate Dehydrogenase.International journal of molecular sciences · 2022Article
- Interpretable machine learning-derived nomogram model for early detection of diabetic retinopathy in type 2 diabetes mellitus: a widely targeted metabolomics study.Nutrition & diabetes · 2022Article
- B vitamin supply in plants and humans: the importance of vitamer homeostasis.The Plant journal : for cell and molecular biology · 2022Review
Corrections and comments
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Authors and funding
10 authors at 6 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Thiamin (vitamin B1) is a pharmacological agent boosting central metabolism through the action of the coenzyme thiamin diphosphate (ThDP). However, positive effects, including improved cognition, of high thiamin doses in neurodegeneration may be observed without increased ThDP or ThDP-dependent enzymes in brain. Here, we determine protein partners and metabolic pathways where thiamin acts beyond its coenzyme role. Malate dehydrogenase, glutamate dehydrogenase and pyridoxal kinase were identified as abundant proteins binding to thiamin- or thiazolium-modified sorbents. Kinetic studies, supported by structural analysis, revealed allosteric regulation of these proteins by thiamin and/or its derivatives. Thiamin triphosphate and adenylated thiamin triphosphate activate glutamate dehydrogenase. Thiamin and ThDP regulate malate dehydrogenase isoforms and pyridoxal kinase. Thiamin regulation of enzymes related to malate-aspartate shuttle may impact on malate/citrate exchange, responsible for exporting acetyl residues from mitochondria. Indeed, bioinformatic analyses found an association between thiamin- and thiazolium-binding proteins and the term acetylation. Our interdisciplinary study shows that thiamin is not only a coenzyme for acetyl-CoA production, but also an allosteric regulator of acetyl-CoA metabolism including regulatory acetylation of proteins and acetylcholine biosynthesis. Moreover, thiamin action in neurodegeneration may also involve neurodegeneration-related 14-3-3, DJ-1 and β-amyloid precursor proteins identified among the thiamin- and/or thiazolium-binding proteins.
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