Why do some organisms use a urea-methylamine mixture as osmolyte? Thermodynamic compensation of urea and trimethylamine N-oxide interactions with protein

Lin, Tiao-Yin; Timasheff, Serge N.

doi:10.1021/bi00208a021

Cited by 372Protein Structure and DynamicsProtein purification and stabilityChemical and Physical Properties in Aqueous Solutions

Why do some organisms use a urea-methylamine mixture as osmolyte? Thermodynamic compensation of urea and trimethylamine N-oxide interactions with protein

Lin, Tiao-Yin, Timasheff, Serge N.·1994·Biochemistry

DOI 10.1021/bi00208a021

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Abstract

Many organisms accumulate low molecular weight substances known as osmolytes when they experience environmental water stress. The main classes of osmolytes are sugars, polyhydric alcohols, amino acids and their derivatives, and methylamines, and all are known to be protein stabilizers. However, marine cartilaginous fishes and the coelacanth use, as osmolytes, a combination of urea and methylamines, i.e., a denaturant and a stabilizer, in a 2:1 molar ratio. Preferential binding and thermal denaturation measurements in the presence of each cosolvent separately and in their mixtures have been carried out using ribonuclease T1 (RNase T1) as the protein. At a 2:1 molar ratio of urea and trimethylamine N-oxide (TMAO), the effects of the two cosolvents on the transition temperature (Tm) were found to be essentially the algebraic sum of their effects when used individually. Preferential interaction measurements of urea, TMAO and urea in its 2:1 molar ratio mixture with TMAO, have shown that the presence of TMAO has no effect on the interaction of urea with the protein in either the native or the unfolded (reduced carboxymethylated RNase T1) state. The preferential interaction of TMAO in the presence of urea could not be measured for technical reasons. Calculations of transfer free energy in the two end states of the denaturation reaction have shown that 2 M urea destabilizes RNase T1 by 3.8 +/- 0.3 kcal/mol whether 1 M TMAO is present or not. The contribution of 1 M TMAO to stabilization is calculated to be 3.1 kcal/mol in the presence of 2 M urea and is measured to be 2.7 kcal/mol in its absence.

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In organisms that concentrate urea as an osmolyte and buoyancy factor, TMAO restores proteins to their native structure and allows them to regain enzyme function lost because of urea.
“In organisms that concentrate urea as an osmolyte and buoyancy factor, TMAO has been shown to restore proteins to their native structure and allow them to regain their enzyme function that has been lost because of the presence of urea [4,5].”
From Trimethylamine N-oxide: the good, the bad and the unknown. (2016) · cites this paper as [4]

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Authors: Lin, T.-Y., & Timasheff, S. N.
Affiliations: Brandeis University (US)
Venue: Biochemistry
Publisher: American Chemical Society (ACS)
Published: 1994-10
Volume: 33
Issue: 42
Pages: 12695-12701
ISSN: 0006-2960 (ISSN-L)
1520-4995
DOI: 10.1021/bi00208a021
OpenAlex: W1985015433
Cited by: 371
References: 0
Citations by year: 2026: 6 · 2025: 12 · 2024: 11 · 2023: 6 · 2022: 13 · 2021: 11 · 2020: 11 · 2019: 21 · 2018: 12 · 2017: 20 · 2016: 15 · 2015: 14 · 2014: 13 · 2013: 18 · 2012: 17
FWCI: 2.02
Type: journal article
Language: en
Open access: closed
Locations: Biochemistry (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (5r01gm014603-29)
National Institute of General Medical Sciences (GM 14603)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein purification and stability
Physical Sciences › Chemical Engineering › Filtration and Separation › Chemical and Physical Properties in Aqueous Solutions
Keywords: osmolytes, urea, trimethylamine N-oxide, methylamine, protein stabilization, ribonuclease T1, thermal denaturation, preferential interactions, transfer free energy, coelacanth, water stress, cosolvents
MeSH terms: Ribonuclease T1, Methylamines, Models, Chemical, Osmolar Concentration, Protein Denaturation, Solvents, Thermodynamics, Urea, Water, Water-Electrolyte Balance

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Why do some organisms use a urea-methylamine mixture as osmolyte? Thermodynamic compensation of urea and trimethylamine N-oxide interactions with protein

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