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. (c) 2021 Elsevier B.V. and Societe Francaise de Biochimie et Biologie Moleculaire (SFBBM). All rights reserved.

Automated summary

Aquaporins, important channel proteins, can transport water and various solutes, with recent studies indicating that some aquaporins also exhibit lactate permeability. Lactate undergoes a pH-dependent protonation equilibrium in aqueous solution, likely representing the substrate form passing through aquaporin channels. It is noteworthy that some aquaporins can better facilitate lactate/lactic acid transport even with low proton availability.