Why is Glycine not a Part of the Osmoticum in the Urea-rich Cells?

Abstract

Kidney cells of animals including human and marine invertebrates contain high amount of the protein denaturant, urea. Methylamine osmolytes are generally believed to offset the harmful effects of urea on proteins in vitro and in vivo. In this study we have investigated the possibility of glycine to counteract the effects of urea on three proteins by measuring thermodynamic stability, ΔGD° and functional activity parameters (K(m) and k(cat)). We discovered that glycine does not counteract the effects of urea in terms of both protein stability and functional activity. We also observed that the glycine alone is compatible with enzymes function and increases protein stability in terms of T(m) (midpoint of thermal denaturation) to a great extent. Our study indicates that a most probable reason for the absence of a stabilizing osmolyte, glycine in the urea-rich cells is due to the fact that this osmolyte is non-protective to macromolecules against the hostile effects of urea, and hence is not chosen by evolutionary selection pressure.

Analysis of Eisenia fetida earthworm responses to sub-lethal C60 nanoparticle exposure using 1H-NMR based metabolomics

“…The osmolytes betaine (Yancey et al, 1982), glycine (Dawson et al, 1998;Khan et al, 2013;Miyawaki et al, 2014;Ou et al, 2002) and myo-inositol (Khan et al, 2013;Miyawaki et al, 2014) and, HEFS, an earthworm specific compound that is proposed to be Percent Changes Fig. 4.…”

Trimethylamine N-Oxide (TMAO): a Unique Counteracting Osmolyte?

“…• Glycine-but only at relatively high concentrations-can stabilize many proteins against high temperatures and freeze-thaw cycling and, like TMAO, is typically said to act via the preferential exclusion mechanism [67]). However, glycine shows no positive or negative effects on protein stability/folding in the presence of urea [68] or elevated pressure [69][70] on several proteins. In these ways glycine is truly 'compatible' in the sense of non-perturbing.…”