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The following message was posted to: PharmPK
Dear All,
I'm working on trying to mathematically modelling the efflux function
of an efflux transporter. Vmax/Km parameters are hard to come by for
this partic. transporter, and I'm thinking of looking at the
catalytic cycle of the transporter and relating number of ATP
molecules hydrolysed to number of substrate molecules effluxed as a
crude first step.
Can anyone give me any ideas and suggestions on this method?
In particular, I'm not sure how to link the relationship between ATP
hydrolysis and efflux to a time parameter to give me a kinetic
parameter.
Any suggestions?
Many thanks
Raj
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Hi Raj
if you are talking about the P-gp efflux pump it is not very vise to
choose this method.
it is common knowledge that quite many molecules are activating ATP
and actually aren't substrates.
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The following message was posted to: PharmPK
Dear Raj,
To link ATP hydrolysis and efflux for the same cells you need to know
total protein and the transporter content in the cells. Here are the two
references, which can help you to answer your question.
Gatlik-Landwojtowicz E, Aanismaa P, Seelig A.
The rate of P-glycoprotein activation depends on the metabolic state of
the cell.
Biochemistry. 2004 Nov 23;43(46):14840-51.
Ambudkar SV, Cardarelli CO, Pashinsky I, Stein WD.
Relation between the turnover number for vinblastine transport and for
vinblastine-stimulated ATP hydrolysis by human P-glycoprotein.
J Biol Chem. 1997 Aug 22;272(34):21160-6.
Regards
Ewa
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