Organic osmolytes are small solutes used by cells of numerous water-stressed organisms
and tissues to maintain cell volume. Similar compounds are accumulated by some organisms
in anhydrobiotic, thermal and possibly pressure stresses. These solutes are amino
acids and derivatives, polyols and sugars, methylamines, methylsulfonium compounds
and urea. Except for urea, they are often called ;compatible solutes', a term indicating
lack of perturbing effects on cellular macromolecules and implying interchangeability.
However, these features may not always exist, for three reasons. First, some of these
solutes may have unique protective metabolic roles, such as acting as antioxidants
(e.g. polyols, taurine, hypotaurine), providing redox balance (e.g. glycerol) and
detoxifying sulfide (hypotaurine in animals at hydrothermal vents and seeps). Second,
some of these solutes stabilize macromolecules and counteract perturbants in non-interchangeable
ways. Methylamines [e.g. trimethylamine N-oxide (TMAO)] can enhance protein folding
and ligand binding and counteract perturbations by urea (e.g. in elasmobranchs and
mammalian kidney), inorganic ions, and hydrostatic pressure in deep-sea animals. Trehalose
and proline in overwintering insects stabilize membranes at subzero temperatures.
Trehalose in insects and yeast, and anionic polyols in microorganisms around hydrothermal
vents, can protect proteins from denaturation by high temperatures. Third, stabilizing
solutes appear to be used in nature only to counteract perturbants of macromolecules,
perhaps because stabilization is detrimental in the absence of perturbation. Some
of these solutes have applications in biotechnology, agriculture and medicine, including
in vitro rescue of the misfolded protein of cystic fibrosis. However, caution is warranted
if high levels cause overstabilization of proteins.