Osmolytes offset the urea's effect on protein structure and function

Abstract

High concentrations of urea are accumulated intracellularly in marine elasmobranchs and inner medullary region of mammalian kidney. It has been found that methylamine organic osmolytes are accumulated in concert with urea to counteract the deleterious effects of urea on the structure and function of macromolecules like proteins and nucleic acids. Both these co-solutes have been found to accumulate intracellularly in a molar ratio range of 2:1-3:2. Effects of urea and methylamines on the stability and functional activity of proteins at this ratio have been shown to be algebraically additive. Urea-methylamine counteraction phenomenon has been examined at various aspects like structural, functional and thermodynamic levels. Recently a number of key molecular insights regarding the urea-methylamine interaction with proteins have been revealed from various atomic level counteraction and simulation studies. In this chapter, all important developments have been discussed with up-to-date information. Some non- methylated osmolytes (myo-inositol, taurine, sorbitol, trehalose, etc.) have also been claimed to efficiently counter the urea's effects on proteins. For this, a detailed discussion has been devoted to these promising alternate urea-counteraction systems like urea-NaCl, urea-myo-inositol and urea-trehalose. Avenues that warrant future attention in this area have also been summarized.