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Living with urea stress

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Abstract

Intracellular organic osmolytes are present in certain organisms adapted to harsh environments. These osmolytes protect intracellular macromolecules against denaturing environmental stress. In contrast to the usually benign effects of most organic osmolytes, the waste product urea is a well-known perturbant of macromolecules. Although urea is a perturbing solute which inhibits enzyme activity and stability, it is employed by some species as a major osmolyte. The answer to this paradox was believed to be the discovery of protective osmolytes (methylamines). We review the current state of knowledge on the various ways of counteracting the harmful effects of urea in nature and the mechanisms for this. This review ends with the mechanistic idea that cellular salt (KCl/NaCl) plays a crucial role in counteracting the effects of urea, either by inducing required chaperones or methylamines, or by thermodynamic interactions with urea-destabilised proteins. We also propose future opportunities and challenges in the field.

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Abbreviations

α-LA:

α-lactalbumin

DMSO:

dimethyl sulphoxide

GPC:

glycerophosphoryl choline

Hsp:

heat shock protein

MDCK:

Madine-Darby canine kidney

mIMCD:

murine inner medullar collecting duct

NMR:

nuclear magnetic resonance

PCD:

papillary collecting duct

PI:

papillary interstitial

RNase-A:

ribonuclease-A

TMAO:

trimethylamine N-oxide

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Authors and Affiliations

  1. Division of Population Science, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA, 19111, USA

    Laishram R. Singh

  2. Center for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, 110 025, India

    Tanveer Ali Dar & Faizan Ahmad

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  1. Laishram R. Singh
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  2. Tanveer Ali Dar
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  3. Faizan Ahmad
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Correspondence to Faizan Ahmad.

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Singh, L.R., Dar, T.A. & Ahmad, F. Living with urea stress. J Biosci 34, 321–331 (2009). https://doi.org/10.1007/s12038-009-0036-0

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