Lactic Acid Permeability of Aquaporin-9 Enables Cytoplasmic Lactate Accumulation via an Ion Trap.
Level 5 - mechanism / opinion, no new human data
In vitro bench study using a yeast expression system without human clinical data.
PubMed 35054513 · doi:10.3390/life12010120
What was done
Researchers expressed human aquaporin-9 (AQP9) and human monocarboxylate transporter 1 (MCT1) in a yeast expression system to measure and compare the uptake kinetics and intracellular accumulation of radiolabeled L-lactate/L-lactic acid under varying external pH conditions.
What was found
The abstract reports no exact numerical values, kinetic parameters, or statistical measures. Uptake mediated by AQP9 was slower than MCT1 at neutral and slightly acidic pH due to low availability of the neutral substrate form. At a pH matching the pKa of L-lactic acid, uptake via AQP9 exceeded that of MCT1. Furthermore, while MCT1 reached an equilibrium balancing intracellular and extracellular L-lactate/proton concentrations, AQP9-mediated transport exhibited linear uptake, enabling higher intracellular accumulation via an ion trap mechanism following intracellular dissociation.
Why it matters
This study delineates the biophysical mechanism by which AQP9 transports uncharged lactic acid, showing how it can drive cytoplasmic lactate accumulation in acidic microenvironments, such as those found in certain brain tumors.
Limits
Findings rely entirely on a heterologous yeast expression model rather than mammalian or human tumor cell systems. The abstract does not report quantitative transport rates, affinity constants, sample replicates, or statistical variance. The model does not capture complex in vivo physiological factors, such as cellular buffering capacity or the presence of concurrent transport pathways.
Cited by
- supports Lactic acid has a pKa of approximately 3, meaning it is completely dissociated into lactate anion and a proton at physiological pH.