ArticleProceedings of the National Academy of Sciences of the United States of America2014
Microscopic insights into the protein-stabilizing effect of trimethylamine N-oxide (TMAO).
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
81 citing papers in PubMed, 1 synthesis or guideline pooled it, 250 citations in OpenAlex.
- Trimethylamine-N-oxide has prognostic value in coronary heart disease: a meta-analysis and dose-response analysis.BMC cardiovascular disorders · 2020Pooled it
- Trimethylamine-N-oxide: the microbial cue in immune-mediated disorders.Trends in endocrinology and metabolism: TEM · 2026Review
- Characterization of Liquid-Liquid Phase Separation of Companion of Cellulose Synthases under Stress Mimicking Conditions.bioRxiv : the preprint server for biology · 2026Article
- Proteoform-Resolved Cross-Linking Reveals Environment-Dependent Structural Effects of α-Synuclein S129 Phosphorylation.Journal of the American Chemical Society · 2026Article
- First Hydration Shell Integrity: Key to Protein Stability.Journal of the American Chemical Society · 2026Article
- Article
- Elevated serum trimethylamine N-oxide (TMAO) and trimethyllysine in patients with amyotrophic lateral sclerosis (ALS): An exploratory case-control study.IBRO neuroscience reports · 2026Article
- The effect of TMAO on aging-associated cardiovascular and metabolic pathways and emerging therapies.Molecular and cellular biochemistry · 2025Review
- Urea, TMAO, betaine and other osmolytes as endogenous diuretics in heart failure and hypertension.Heart failure reviews · 2025Review
- Tau Oligomers in Alzheimer's Disease: Modulation Effect of Osmolytes on Amplified Brain-Derived Tau Oligomers.ACS chemical neuroscience · 2025Article
- Trimethylamine N-Oxide Mitigates Perioperative Neurocognitive Disorders via ANXA1 Nuclear Translocation and M2 Microglial Polarization in the Hippocampus.CNS neuroscience & therapeutics · 2025Article
- The Determination of Trimethylamine N-Oxide and Organic Acids Connected with Gut Microbiota in the Urine of Parkinson's Disease Patients: A Pilot Study.International journal of molecular sciences · 2025Article
- De Novo Design of Proteins for Autocatalytic Isopeptide Bond Formation.Journal of the American Chemical Society · 2025Article
- Interaction studies unveil potential binding sites on bovine serum albumin for gut metabolite trimethylamine n-oxide (TMAO).BMC chemistry · 2025Article
- Article
- Trimethylamine N-oxide (TMAO) doubly locks the hydrophobic core and surfaces of protein against desiccation stress.Protein science : a publication of the Protein Society · 2024Article
- The Brain-Gut Axis, an Important Player in Alzheimer and Parkinson Disease: A Narrative Review.Journal of clinical medicine · 2024Review
- TMAO enhances TNF-α mediated fibrosis and release of inflammatory mediators from renal fibroblasts.Scientific reports · 2024Article
- Article
- Anisotropic dynamics of an interfacial enzyme active site observed using tethered substrate analogs and ultrafast 2D IR spectroscopy.The Journal of chemical physics · 2023Article
21 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Although it is widely known that trimethylamine N-oxide (TMAO), an osmolyte used by nature, stabilizes the folded state of proteins, the underlying mechanism of action is not entirely understood. To gain further insight into this important biological phenomenon, we use the C≡N stretching vibration of an unnatural amino acid, p-cyano-phenylalanine, to directly probe how TMAO affects the hydration and conformational dynamics of a model peptide and a small protein. By assessing how the lineshape and spectral diffusion properties of this vibration change with cosolvent conditions, we are able to show that TMAO achieves its protein-stabilizing ability through the combination of (at least) two mechanisms: (i) It decreases the hydrogen bonding ability of water and hence the stability of the unfolded state, and (ii) it acts as a molecular crowder, as suggested by a recent computational study, that can increase the stability of the folded state via the excluded volume effect.
Indexed as
Identifiers
What OpenQuestion holds
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.