Experimental evidence and physiological significance of the ascorbate passive diffusion through the lipid bilayer

•Vitamin C has high affinity towards the membrane interface.•Vitamin C at physiological concentrations diffuses across the lipid bilayer.•The lipid bilayer permeability coefficient for vitamin C equals to 10−7 - 10-8 cm2/s.•The vitamin C passive diffusion across the lipid bilayer is critical for its biodistribution. The diverse range of functions performed by ascorbate in many metabolic processes requires its effective redistribution between various aqueous body compartments. It is believed that this hydrophilic molecule needs protein transporters for crossing the biological membrane barriers. Any effective model reflecting the ascorbate distribution within the body requires bi-directional fluxes, but only the ascorbate transporters facilitating its intake by cells have been identified to date. The cellular efflux of this molecule still lacks proper mechanistic explanation, nevertheless data suggesting possible passive ascorbate transport recently appeared. In the paper, we provide experimental evidences that ascorbate associates efficiently with the lipid bilayer interface and slowly crosses its hydrophobic core. The measured logPmembrane/water and membrane permeability coefficient equal to 3 and 10−7 – 10−8 cm/s, respectively. The ascorbate passive diffusion across the lipid bilayer provides the missing element needed for the construction of a consistent physiological model describing the ascorbate local homeostasis. The model was effectively used for the construction of the mechanistic description of the processes, which facilitate the ascorbate homeostasis in the brain.