Membrane Permeabilities of Ascorbic Acid and Ascorbate

Abstract

Vitamin C (VC)—a collective term for the different oxidation and protonation forms of ascorbic acid (AscH)—is an essential micronutrient that serves as (i) a potent antioxidant and (ii) a cofactor of a manifold of enzymatic processes. Its role in health is related to redox balance maintenance, which is altered in diseases such as obesity, cancer, neurodegenerative diseases, hypertension, and autoimmune diseases. Despite its importance, VC uptake has been poorly investigated. Available literature values for the passive membrane permeability P of lipid bilayers for AscH scatter by about 10 orders of magnitude. Here, we show by voltage clamp that P− of AscH’s anionic form (ascorbate Asc−) is negligible. To cross the membrane, Asc− picks up a proton in the membrane vicinity and releases it on the other side of the membrane. This leads to a near-membrane pH drop that was visualized by scanning pH microelectrodes. The AscH concentration dependent pH profiles indicated P = 1.1 ± 0.1 × 10−8 cm/normals. Thus, AscH’s P is comparable to that of sorbitol and much lower than that of other weak acids like acetic acid or salicylic acid. The observation suggests that the capacity of the passive transcellular transport pathway across the lipid matrix does not suffice to ensure the required VC intake from the gastrointestinal tract.

Passive Permeability of Planar Lipid Bilayers to Organic Anions

“…The former, limited by the diffusion through the membrane interior, provided the membrane permeability (0.3 cm/s), whereas the latter provided the permeability P UWL through the UWL (7.4 Â 10 À4 cm/s). Using the TPB diffusion constant D w in water (43) of 8 Â 10 À6 cm 2 /s and the simple relation P w ¼ D w /d, the overall thickness of the unstirred layers d was estimated to be around 108 mm-a value that is consistent with direct observations of d by scanning electrochemical microscopy (51). Increased peak and steady-state conductivities due to stirring were observed ( Fig.…”

The Role of Phosphatidylethanolamine Adducts in Modification of the Activity of Membrane Proteins under Oxidative Stress

“…The cell's own systems of defense from oxidative stress include different ROS detoxification systems, such as superoxide dismutase, catalase, and glutathione peroxidase (for detailed reviews see [12,17]). Several lipophilic or water-soluble, membrane-permeable molecules (tocopherol, carotenoids, anthocyanins, polyphenols, and uric and ascorbic acid [18]) can work as endogenous or nutritional antioxidants (for review see [19]).…”

On the physiological and cellular homeostasis of ascorbate

“…This causes a serious difficulty in the construction of physiological or cellular models for water-soluble ascorbate homeostasis. Recently, it has been demonstrated that ascorbate is able to diffuse through model lipid bilayers [29,30]. This discovery provides a missing element for the construction of an effective and coherent conceptual model describing the mechanisms leading to the generation of ascorbate distribution within various body aqueous compartments.…”

“…The equation shows that the intracellular ascorbate concentration is generated by a specified number of SVCT transporters present in the plasma membrane. The low value of the ascorbate membrane permeability constant (10 − 8 cm/s [29]) may indicate that a relatively small number of SVCT transporters is required for maintenance of the ascorbate intracellular level. A specific SVCT location on the plasma membrane is dictated by the type of adjacent aqueous phase.…”

“…Recently, it was demonstrated, and later confirmed, that ascorbate crosses the biological membrane by passive diffusion through the lipid bilayer [29,30]. The finding provides the missing element for the construction of an effective conceptual model describing the spatio-temporal ascorbate distribution between body aqueous compartments.…”