Implications of the Alternating Access Model for Organic Anion Transporter Kinetics

Implications of the Alternating Access Model for Organic Anion Transporter Kinetics Many transport proteins, including the clinically important organic anion transporters (OATs), appear to function via an “alternating access” mechanism. In analyzing the kinetics of these transporters, the terms K m and V max are often treated in the field as denoting, respectively, the affinity of the substrate for the transporter and the turnover (conformational switch) rate of the substrate–transporter complex. In fact, the expressions for both these parameters have very complex forms comprising multiple rate constants from conformational switch as well as association/dissociation steps in the cycling of the transporter and, therefore, do not have straightforward physical meanings. However, if the rapid equilibrium assumption is made (namely, that the association/dissociation steps occur far more rapidly than the conformational switch steps), these expressions become greatly simplified and their physical meaning clear, though still distinct from the conventional interpretations. V max will be a function of not just the rate of substrate–transporter complex turnover but also the rate of the “return” conformational switch and will vary largely with the slower of these two steps (the rate-limiting step). K m will be seen to be related to substrate affinity by a term that varies inversely with the substrate–transporter complex turnover rate, essentially because the greater this rate, the greater the extent to which transporters will be distributed in a conformation inaccessible to substrate. Here, an intuitive approach is presented to demonstrate these conclusions. The phenomena of trans-stimulation and trans-inhibition are discussed in the context of this analysis. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png The Journal of Membrane Biology Springer Journals

Implications of the Alternating Access Model for Organic Anion Transporter Kinetics

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Publisher
Springer-Verlag
Copyright
Copyright © 2008 by Springer Science+Business Media, LLC
Subject
Life Sciences; Human Physiology ; Biochemistry, general
ISSN
0022-2631
eISSN
1432-1424
D.O.I.
10.1007/s00232-008-9137-1
Publisher site
See Article on Publisher Site

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