title: Testing the paradigm that the denaturing effect of urea on protein stability is offset by methylamines at the physiological concentration ratio of 2:1 (urea:methylamines).
abstract: The intra- and extracellular urea concentration in many organisms is sufficiently high to destabilize (inhibit) many proteins, yet organisms survive and function. The generally accepted explanation is the counteracting hypothesis, which holds that methylamines stabilize proteins and oppose the deleterious effect of urea. The two osmolytes are typically found at 2:1 concentration ratio (urea:methylamine) under physiological conditions. Does this mean that this ratio holds for all proteins in a cell? The present study tests the counteracting hypothesis by determining the effects of urea and methylamines (trimethylamine N-oxide and sarcosine), singly and in combination at a concentration ratio of 2:1 (urea:methylamine) on the thermal denaturation equilibrium, native state<-->denatured state of three different proteins (alpha-lactalbumin, lysozyme and Ribonuclease-A). We show here that the molar concentration of a methylamine required to offset the denaturing effect of urea at a given concentration is different for different proteins.
authors.affiliation: Department of Biosciences, Jamia Millia Islamia, Jamia Nagar, New Delhi 110 025, India.
authors.forename: Laishram Rajendrakumar
authors.initials: LR
authors.lastname: Singh
authors.forename: Tanveer
authors.initials: T
authors.lastname: Ali Dar
authors.forename: Inamul
authors.initials: I
authors.lastname: Haque
authors.forename: Farah
authors.initials: F
authors.lastname: Anjum
authors.forename: Ali Akbar
authors.initials: AA
authors.lastname: Moosavi-Movahedi
authors.forename: Faizan
authors.initials: F
authors.lastname: Ahmad
mesh_terms: D004347:Drug Interactions; D004795:Enzyme Stability / Q000187:drug effects; D007768:Lactalbumin / Q000737:chemistry / Q000378:metabolism; D008744:Methylamines / Q000737:chemistry* / Q000494:pharmacology*; D009113:Muramidase / Q000737:chemistry / Q000378:metabolism; D009994:Osmolar Concentration; D011489:Protein Denaturation / Q000187:drug effects*; D012259:Ribonuclease, Pancreatic / Q000737:chemistry / Q000378:metabolism; D013816:Thermodynamics; D014508:Urea / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D008744:Methylamines; D014508:Urea; D007768:Lactalbumin; D012259:Ribonuclease, Pancreatic; D009113:Muramidase