ArticleThe Journal of biological chemistry2015
Interaction of α-Lipoic Acid with the Human Na+/Multivitamin Transporter (hSMVT).
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 25 citations in OpenAlex.
- Role of lipoic acid in multiple sclerosis.CNS neuroscience & therapeutics · 2022Pooled it
- A Randomized Controlled Trial of Long-Term (R)-α-Lipoic Acid Supplementation Promotes Weight Loss in Overweight or Obese Adults without Altering Baseline Elevated Plasma Triglyceride Concentrations.The Journal of nutrition · 2020Trial
- Structural basis for multivitamin recognition and transport by human SMVT.Nature communications · 2026Article
- Functional partitioning of lipoic acid decouples cellular abundance from mitochondrial utilization.bioRxiv : the preprint server for biology · 2026Article
- Enhancing Nutraceutical Efficacy: The Role of M.A.T.R.I.S. Technology in Modulating Intestinal Release of Lipoic Acid and L-Carnitine.International journal of molecular sciences · 2025Article
- Much More than Nutrients: The Protective Effects of Nutraceuticals on the Blood-Brain Barrier in Diseases.Nutrients · 2025Review
- Lipoic acid attachment to proteins: stimulating new developments.Microbiology and molecular biology reviews : MMBR · 2024Review
- α-Lipoic acid chemistry: the past 70 years.RSC advances · 2023Review
- Insight into the mechanism of HProceedings of the National Academy of Sciences of the United States of America · 2023Article
- Alpha lipoic acid reverses scopolamine-induced spatial memory loss and pyramidal cell neurodegeneration in the prefrontal cortex of Wistar rats.IBRO neuroscience reports · 2022Article
- Heterologous (Over) Expression of Human SoLute Carrier (SLC) in Yeast: A Well-Recognized Tool for Human Transporter Function/Structure Studies.Life (Basel, Switzerland) · 2022Review
- Lipoic acid. Kinetics and pluripotent biological properties and derivatives.Molecular biology reports · 2021Review
- Comparison of Coated and Immobilized Chiral Stationary Phases Based on Amylose tris-[(Molecules (Basel, Switzerland) · 2021Article
- Mitochondrial medicine therapies: rationale, evidence, and dosing guidelines.Current opinion in pediatrics · 2020Review
- Genetic defect of the sodium-dependent multivitamin transporter: A treatable disease, mimicking biotinidase deficiency.JIMD reports · 2019Article
- Ion and pH Sensitivity of a TMBIM CaStructure (London, England : 1993) · 2019Article
- Mitochondrial Dysfunction and Alpha-Lipoic Acid: Beneficial or Harmful in Alzheimer's Disease?Oxidative medicine and cellular longevity · 2019Review
- The LeuT-fold neurotransmitter:sodium symporter MhsT has two substrate sites.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Exploring Substrate Binding in the Extracellular Vestibule of MhsT by Atomistic Simulations and Markov Models.Journal of chemical information and modeling · 2018Article
- Mutations in SLC5A6 associated with brain, immune, bone, and intestinal dysfunction in a young child.Human genetics · 2017Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
The human Na(+)/multivitamin transporter (hSMVT) has been suggested to transport α-lipoic acid (LA), a potent antioxidant and anti-inflammatory agent used in therapeutic applications, e.g. in the treatment of diabetic neuropathy and Alzheimer disease. However, the molecular basis of the cellular delivery of LA and in particular the stereospecificity of the transport process are not well understood. Here, we expressed recombinant hSMVT in Pichia pastoris and used affinity chromatography to purify the detergent-solubilized protein followed by reconstitution of hSMVT in lipid bilayers. Using a combined approach encompassing radiolabeled LA transport and equilibrium binding studies in conjunction with the stabilized R-(+)- and S-(-)-enantiomers and the R,S-(+/-) racemic mixture of LA or lipoamide, we identified the biologically active form of LA, R-LA, to be the physiological substrate of hSMVT. Interaction of R-LA with hSMVT is strictly dependent on Na(+). Under equilibrium conditions, hSMVT can simultaneously bind ~2 molecules of R-LA in a biphasic binding isotherm with dissociation constants (Kd) of 0.9 and 7.4 μm. Transport of R-LA in the oocyte and reconstituted system is exclusively dependent on Na(+) and exhibits an affinity of ~3 μm. Measuring transport with known amounts of protein in proteoliposomes containing hSMVT in outside-out orientation yielded a catalytic turnover number (kcat) of about 1 s(-1), a value that is well in agreement with other Na(+)-coupled transporters. Our data suggest that hSMVT-mediated transport is highly specific for R-LA at our tested concentration range, a finding with wide ramifications for the use of LA in therapeutic applications.
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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.