Water, Proteins, and Volume Regulation: Molecular Mechanisms of Hydration and Oncotic Balance
DOI:
https://doi.org/10.12775/PPS.2025.26.66523Keywords
protein hydration, urea, oncotic pressure, volume regulation, hypoproteinemia, aquaporins, Na⁺/K⁺-ATPase, Starling balance, vasopressin, water homeostasisAbstract
Background: Water is the fundamental basis of life and an absolute prerequisite for the existence of proteins and all biological structures. During evolution, an extraordinarily complex multilevel system of water homeostasis has developed in the human body, with diverse executive mechanisms at each level of biological organization.
Objective: Comprehensive analysis of molecular, cellular, and systemic mechanisms of water-protein interactions in the context of human physiology, with particular emphasis on the role of urea as a regulator of protein hydration, the function of plasma proteins in maintaining oncotic pressure, and the pathophysiology of hepatic hypoproteinemia.
Methods: Narrative literature review with systematic search in PubMed, Scopus, and Web of Science databases for the period 1980-2025. Over 80 scientific sources were analyzed, including original research, systematic reviews, and clinical studies. Special attention was paid to the works of Professor A.I. Gozhenko and co-authors on water-salt homeostasis.
Results: Protein hydration layers consist of several zones with varying degrees of ordering (first layer 0.25-0.35 nm, second layer 0.35-0.6 nm), with the rotational relaxation time of water molecules in the first layer being 2-5 times longer than in bulk water. Urea demonstrates a concentration-dependent dichotomy: at physiological concentrations (5-500 mM) it functions as a compatible osmolyte, while at high concentrations (6-8 M) it acts as a denaturant. Albumin, comprising 60% of plasma protein mass, generates 75-80% of oncotic pressure (25-28 mmHg) due to the Donnan effect and nonlinear dependence π = RT·C·(1+kC). Aquaporins transport up to 3×10⁹ water molecules/s, while Na⁺/K⁺-ATPase creates ionic gradients by exporting 3 Na⁺ and importing 2 K⁺ per ATP molecule. Vasopressin, via V2 receptors, activates the cAMP-PKA cascade, leading to AQP2 phosphorylation at Ser256 and its translocation to the apical membrane. Hepatic hypoalbuminemia (<25-30 g/L) disrupts Starling balance, activating RAAS and ADH, which paradoxically exacerbates edema.
Conclusions: Water homeostasis is maintained through hierarchical integration of molecular (protein hydration, urea role), cellular (aquaporins, Na⁺/K⁺-ATPase), tissue (Starling balance, oncotic pressure), and systemic (hypothalamic-pituitary-renal axis) mechanisms. Disruption at any level leads to a cascade of pathological changes, emphasizing the need for an integrative approach to the diagnosis and treatment of water balance disorders.
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