Lysosome membrane permeability to anions

Abstract

The permeability of rat liver lysosomes to some inorganic and aliphatic organic anions was investigated, using an osmotic-protection methodology. Lysosomes were incubated at 25 degreesC in 250 mOsm solutions of potassium salts of the anions, in the presence of valinomycin, and the latency of lysosomal hexosaminidase measured at intervals. Lysosomes suspended in 250 mM sucrose at 25 degreesC were stable for up to 4 h. When suspended in 250 mOsm solutions of potassium salts of inorganic acids, latency was lost at rates indicating anion permeance decreasing in the order thiocyanate, nitrate and iodide>bromide>chloride>sulfate. This rank order does not correspond with the anion selectivity of any known anion transporter, and is closer to that of the lyotropic series. Results with the potassium salts of aliphatic organic acids indicate little correlation between permeation and hydrocarbon chain length, although formate was more rapidly permeant than acetate and its higher homologs. By contrast, oxalate was less permeable than other dicarboxylic acids. The presence of one or more hydroxy groups decreased permeance. A correlation between permeance and the acid's lowest pKa suggested that penetration was due principally to the entry of the undissociated acid, but there is evidence that the (much more abundant) singly charged anionic form is also significantly permeant.

Characterization of Aquaporin-6 as a Nitrate Channel in Mammalian Cells

“…Third, AQP6 is not inhibited by known anion channel inhibitors such as DIDS, 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB), niflumic acid, and diphenylamine-2-carboxylic acid (DPC) (3). Interestingly, the permeability sequence is identical to that of lysosomal membranes (25). The acidic pH within the interior of lysosomes is generated and maintained FIG.…”

Carboxylate Surrogates Enhance the Antimycobacterial Activity of UDP-Galactopyranose Mutase Probes

“…18 Still, negatively charged functional groups such as carboxylates are known to hinder diffusion through lipid bilayer membranes. 24, 25 We anticipated that replacing the carboxylic acid with a functional group surrogate would modulate the physicochemical properties of the inhibitor and might enhance its ability to permeate mycobacteria. We identified the N -acylsulfonamide functionality as a promising candidate, as it previously has been employed as a carboxylic acid bioisostere 26 and can successfully mimic phosphate groups.…”

“…The observation that the carboxylate moiety of the 2-aminothiazole inhibitors is crucial for activity against UGM suggests that it mimics the pyrophosphate group . Still, negatively charged functional groups such as carboxylates are known to hinder diffusion through lipid bilayer membranes. , We anticipated that replacing the carboxylic acid with a functional group surrogate would modulate the physicochemical properties of the inhibitor and might enhance its ability to permeate mycobacteria. We identified the N -acylsulfonamide functionality as a promising candidate that was previously employed as a carboxylic acid bioisostere and can successfully mimic phosphate groups. , N -Acylsulfonamides have lower p K a values compared to those of carboxylic acids and are expected to be ionized under physiological conditions .…”

Characterization of Isolated Acidocalcisomes of Trypanosoma cruzi

“…3) showed that there was a requirement, which could not be fulfilled by gluconate, but there was no stringent requirement for chloride. The activity with nitrate may be explicable by diffusion of this anion through the membrane (37); sulfate, in contrast, is less membrane-permeable than chloride (37). Therefore, the acidocalcisome membrane may have an anion channel generally permeable to small anions.…”