Hello

The mechanism and kinetics of p-glycoprotein efflux action of the protein follows a carrier mediated primary active transport mechanism. In this process, the protein pump export needs direct ATP requirement and the energy released from the ATP hydrolysis gives the driving force for extrusion process. The efflux takes place unidirectionally (out of the cells into the extracellular space) and transfers only one molecule at a time. Thus, P-gp is a uniporter carrier protein. in Figure explains the mechanism of action of the competitive and non-competitive (non-transported) inhibitors apart from the P-gp efflux kinetics. While a P-gp substrate binds to protein’s transport site and gets translocated by the protein, competitive inhibitors compete with the substrate drugs for extrusion and occupy all the available protein transport sites leaving no space for the P-gp and substrate interaction. Non-competitive inhibitors neither bind to protein’s transport site nor are translocated by the protein efflux and hence are as well called as non-transported inhibitors. They non-competitively inhibit the protein efflux by binding to an allosteric modulatory site. Since the number of protein carriers is limited, the transport system is capacity limited. The efflux kinetics is described by the equation, as mixed-order kinetics or Michaelis Menten kinetics.

See attached papers for more info,

Good luck.

Karen A. Darbinyan Valuable answer

Dear Khaled Khleifat thank you!

thanks a lot @ Karen

Dear Moira amanda Mubani you're welcome!

Are there any other compounds known to inhibit the ABCB1 ATPase apart from vanadate? as a way of inhibiting pgp activty?