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A Futile Cycle?: Tissue Homeostatic Trans-Membrane Water Co-Transport: Kinetics, Thermodynamics, Metabolic
Charles S Springer1,2,3,4,5, Martin M Pike1,3,5, Thomas M Barbara1
1Advanced Imaging Research Center.
Biorxiv : the Preprint Server for Biology
|April 25, 2024
Summary
Active trans-membrane water cycling (AWC) is synchronized with Na+,K+-ATPase activity, creating a significant outward water pressure gradient. This process is essential for cellular homeostasis, not futile.
Area of Science:
- Cellular Physiology
- Biophysics
- Membrane Transport
Background:
- Historically, trans-membrane water transport was categorized into exchange and net flow.
- Recent studies suggest co-transporters facilitate water movement alongside substrates.
- Active Trans-membrane Water Cycling (AWC) links bidirectional water exchange to Na+,K+-ATPase (NKA) activity.
Approach:
- Analyzed literature data on metabolomics and proteomics for free energy calculations.
- Utilized molecular dynamics simulations and structural data of co-transporters.
- Investigated water/substrate stoichiometries and kinetic coupling of co-transporter reactions.
Key Points:
- A significant outward H2O barochemical gradient exists, comparable to the inward Na+ electrochemical gradient.
- Co-transporter gradients maintain intracellular metabolite concentrations near Michaelis constants.
- Astrocytic pressure changes impact neurotransmitter transport (glutamate, GABA) and synaptic transmission.
Conclusions:
- Active trans-membrane water cycling is a fundamental, non-futile aspect of the cell's NKA system.
- The H2O barochemical steady-state is near chemical equilibrium, regulated by opposing gradients.
- Aquaporins do not dissipate the trans-membrane pressure gradient; their flux is regulated within AWC.
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