Purified liver uptake transporters reveal bicarbonate efflux, not glutathione, as their energy source
- Purified human OATP1B1 and OATP1B3, key liver uptake transporters for many drugs, were placed in artificial vesicles to remove cellular confounders and ask what powers their transport.
- An outward bicarbonate gradient drove accumulation of substrates; glutathione efflux showed no such role. Pairing OATP1B1 with ABCG2 in the same vesicles supported this.
- Mutating His115 in helix 3 uncoupled bicarbonate from uptake. Green tea EGCG boosted OATP1B3 transport in a substrate-dependent way, without other cell proteins.
💡 Points Based on the abstract
Imposed liposome gradients are not hepatocyte physiology: in liver, intracellular bicarbonate is buffered and pH-dependent, so the driving-force claim needs a cellular check. Before this changes DDI thinking, test whether the His115 mutant loses uptake in sandwich-culture hepatocytes, and whether EGCG's substrate-dependent boost shifts statin or bilirubin probe kinetics.