Aquaporins with lactate/lactic acid permeability at physiological pH conditions.

The spectrum of putative and experimentally shown permeants of cellular water and solute channels of the ubiquitous aquaporin family is still increasing. Virtually all AQP substrates, e.g. water, glycerol, urea, hydrogen peroxide, or carbon dioxide, are permanently neutral small molecule compounds. Several reports, however, describe aquaporins that exhibit lactate permeability. Lactate in aqueous solution undergoes a pH-dependent protonation equilibrium with neutral lactic acid, which likely represents the actual substrate form passing the aquaporin channel. Certain aquaporins, however, appear to be better geared for lactate/lactic acid permeability even at low proton availability. Here, we discuss the structural properties of such aquaporins and compare them to the microbial protein family of the formate-nitrite (lactate) transporters that assume the aquaporin fold despite unrelated protein sequences.