Abstract
Human kidney cells are under constant urea stress due to its urine concentrating mechanism. It is believed that the deleterious effect of urea is counteracted by methylamine osmolytes (glycine betaine and glycerophosphocholine) present in kidney cells. A question arises: Do the stabilizing osmolytes, non-methylamines (myo-inositol, sorbitol and taurine) present in the kidney cells also counteract the deleterious effects of urea? To answer this question, we have measured structure, thermodynamic stability (ΔG D o) and functional activity parameters (K m and k cat) of different model proteins in the presence of various concentrations of urea and each non-methylamine osmolyte alone and in combination. We observed that (i) for each protein myo-inositol provides perfect counteraction at 1∶2 ([myo-inositol]:[urea]) ratio, (ii) any concentration of sorbitol fails to refold urea denatured proteins if it is six times less than that of urea, and (iii) taurine regulates perfect counteraction in a protein specific manner; 1.5∶2.0, 1.2∶2.0 and 1.0∶2.0 ([taurine]:[urea]) ratios for RNase-A, lysozyme and α-lactalbumin, respectively.
Highlights
The waste product, urea plays a key role in the osmoregulation of reno-medullary cells in diuretic and antidiuretic conditions
A question arises: Do non-methylamines have the ability to offset the deleterious effect of urea on protein structure and function? In this communication we have investigated the counteractive ability of all the non-methylamine osmolytes present in the osmoticum of the reno-medullary cells in terms of structure, stability and function of three proteins namely, RNase-A, lysozyme and a-lactalbumin (a-LA)
A question arises: Do these results have any relevance to kidney proteins? It has been shown that stabilizing osmolytes including non-methylamines are preferentially excluded from the protein domain [40,41]
Summary
The waste product, urea plays a key role in the osmoregulation of reno-medullary cells in diuretic and antidiuretic conditions. The urea concentration under diuretic condition is 400–600 mM in the mammalian kidneys including human [1] and reaches up to 3– 4 M under antidiuretic conditions [2]. Urea is a chaotropic agent that disrupts noncovalent interactions responsible for the globular structure of proteins [5,6,7,8] and influences enzyme kinetic properties such as maximal velocity (Vmax) and Km [6,7]. In addition to the chaotropic nature, high urea concentration can bring about post-translational modification of large number of proteins either by carbamoylation or carbonylation near physiological pH and temperature [9,10]
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