Naturally occurring osmolytes are one of the most potent stabilizers for many proteins and are capable of reversing protein misfolding and/or aggregation, which are known to be underlying cause of several diseases.

Osmolytes represent different chemical classes that occur naturally such as amino acids (proline and glycine), methylamines (betaine and trimethylamine-N-oxide), and polyols and sugars (sorbitol and sucrose).

amino acids (notably proline), tertiary sulfonium (dimethylsulfoniopropionate (DMSP)) and quaternary ammonium compounds (e.g., glycine betaine, proline betaine (also known as stachydrine), β-alanine betaine, pipecolate betaine (also known as homostachydrine), hydroxypipecolate betaine and choline-O-sulfate, trigonelline (nicotinic acid betaine)), sugar alcohols (mannitol, sorbitol, pinitol).

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natural sources of amino acid vinegar fermentation

Nutrients and bioactive components from vinegar: A fermented and functional food

https://www.sciencedirect.com/science/article/pii/S175646461930605X

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Osmolyte
Osmoregulation
Methyl Doner

Inositol
Betaine

MDCK
Glycerophosphocholine

What’s New About Osmotic Regulation of Glycerophosphocholine

https://journals.physiology.org/doi/full/10.1152/physiol.00009.2009

Intracellular Organic Osmolytes: Function and Regulation

https://www.jbc.org/article/S0021-9258(20)55117-X/fulltext

Naturally occurring organic osmolytes: From cell physiology to disease prevention

https://iubmb.onlinelibrary.wiley.com/doi/10.1002/iub.406

Osmolytes: Wonder molecules to combat protein misfolding against stress conditions

https://www.sciencedirect.com/science/article/abs/pii/S014181302300555X

Osmolytes: A Possible Therapeutic Molecule for Ameliorating the Neurodegeneration Caused by Protein Misfolding and Aggregation

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7022651/

Polyol and sugar osmolytes can shorten protein hydrogen bonds to modulate function

https://www.nature.com/articles/s42003-020-01260-1

Role of Osmolytes in Amyloidosis

https://www.intechopen.com/chapters/65859

Sugar osmolyte inhibits and attenuates the fibrillogenesis in RNase A: An in vitro and in silico characterizations

https://www.sciencedirect.com/science/article/abs/pii/S0141813023042757?via%3Dihub

Basic concepts and practical equations on osmolality: Biochemical approach

https://www.sciencedirect.com/science/article/abs/pii/S0009912016300972

Combinations of Osmolytes, Including Monosaccharides, Disaccharides, and Sugar Alcohols Act in Concert During Cryopreservation to Improve Mesenchymal Stromal Cell Survival

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5125256/

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Osmolyte
Inorganic Ions
Methylamines
Hypertonicity
Hyperosmolality
Protein Backbone
Renal Medulla
Renal Medullary Cells
Aldose Reductase

Ionic Strength
Macromolecular Crowding

Protective Osmolytes
Denaturing Osmolytes

Although many biochemical functions require specific inorganic ions, increasing the concentrations of these ions above those typically found in cells perturbs protein function. In contrast, organic osmolytes have much less effect, i.e. are compatible. Hypertonicity, as results from high NaCl, causes osmotic flux of water out of cells, elevating the concentration of all cellular constituents, including inorganic salts.

High concentrations of protective organic osmolytes stabilize protein structure. The mechanism of stabilization involves strong exclusion of the protective osmolytes from the surface of proteins. On the other hand, denaturing osmolytes accumulate at the surface of proteins. Protective osmolytes push the equilibrium of protein folding toward the native form, whereas denaturing osmolytes push it toward the unfolded form.

What is the sensor of hypertonicity that activates protective osmoregulatory responses in mammalian cells? Hypertonicity causes a rapid decrease in cell volume, an increase in concentration of all intracellular components (including inorganic ions and macromolecules), and reorganization of the cytoskeleton.

Macromolecular crowding and ionic strength, in particular, have profound effects on biochemical processes, which could contribute to the increased ROS, DNA breaks, and altered activity of kinases and other enzymes that are involved in activating TonEBP/OREBP.

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https://en.m.wikipedia.org/wiki/Osmolyte

https://en.m.wikipedia.org/wiki/Inorganic_ions

https://en.m.wikipedia.org/wiki/Ionic_strength

https://en.m.wikipedia.org/wiki/Macromolecular_crowding

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Renal medullary osmolytes NaCl and urea differentially modulate human tubular cell cytokine expression and monocyte recruitment

https://onlinelibrary.wiley.com/doi/full/10.1002/eji.202149723

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Kidney
Medulla
Renal
N-Acetylcysteine (NAC)

Vinegar
Nitrogen
Sulfur
Minerals
Creatinine

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Ole Molly Tea
Osmolyte
O Smolyte
O Smo Lyte
O Small LIte
Old Small Light