Trimethylamine-N-oxide (TMAO) and urea
represent
the extremes among the naturally occurring organic osmolytes in terms
of their ability to stabilize/destabilize proteins. Their mixtures
are found in nature and have generated interest in terms of both their
physiological role and their potential use as additives in various
applications (crystallography, drug formulation, etc.). Here we report
experimental density and activity coefficient data for aqueous mixtures
of TMAO with urea. From these data we derive the thermodynamics and
solvation properties of the osmolytes, using Kirkwood–Buff
theory. Strong hydrogen-bonding at the TMAO oxygen, combined with
volume exclusion, accounts for the thermodynamics and solvation of
TMAO in aqueous urea. As a result, TMAO behaves in a manner that is
surprisingly similar to that of hard-spheres. There are two mandatory
solvation sites. In plain water, these sites are occupied with water
molecules, which are seamlessly replaced by urea, in proportion to
its volume fraction. We discuss how this result gives an explanation
both for the exceptionally strong exclusion of TMAO from peptide groups
and for the experimentally observed synergy between urea and TMAO.
The kidney uses mixtures of five osmolytes to counter the stress induced by high urea and NaCl concentrations. The individual roles of most of the osmolytes are unclear, and three of the five have not yet been thermodynamically characterized. Here, we report partial molar volumes and activity coefficients of glycerophosphocholine (GPC), taurine, and myo-inositol. We derive their solvation behavior from the experimental data using Kirkwood-Buff theory. We also provide their solubility data, including solubility data for scyllo-inositol. It turns out that renal osmolytes fall into three distinct classes with respect to their solvation. Trimethyl-amines (GPC and glycine-betaine) are characterized by strong hard-sphere-like self-exclusion; urea, taurine, and myo-inositol have a tendency toward self-association; sorbitol and most other nonrenal osmolytes have a relatively constant, intermediate solvation that has components of both exclusion and association. The data presented here show that renal osmolytes are quite diverse with respect to their solvation patterns, and they can be further differentiated based on observations from experiments examining their effect on macromolecules. It is expected, based on the available surface groups, that each renal osmolyte has distinct effects on various classes of biomolecules. This likely allows the kidney to use specific combinations of osmolytes independently to fine-tune the chemical activities of several types of molecules.
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