Almost incredibly, a sedentary adult makes and uses 40 kg of ATP per day! ATP is made by the F0-F1 ATPase, a molecular motor with a rotating shaft and fixed "stator". One end of the shaft, F0, is buried in the mitochondrial inner membrane where the proton gradient causes it to rotate. A single gamma subunit connects the F0 to three alpha and beta subunits, together F1, which are responsible for synthesizing ATP from ADP and Pi (H2PO4-). As a catalytic motor and not just a catalyst, the F0-F1 ATPase is able to increase the rate of reaction away from the equilibrium (which strongly favors the reverse reaction, hydrolysis, because the concentrations of reactants and product in mitochondria are similar). The gamma subunit rotates too slowly, in the microsecond-to-millisecond range, for standard molecular dynamics simulation. To solve this, the authors applied "biasing forces" as the motor moved and assumed these forces would not change the mechanism. Positively charged amino acids on the gamma subunit attract negative amino acids on beta subunit, producing smooth and efficient ionic coupling. Rotation of the gamma subunit induces the opening of the beta subunits. The beta subunit closes spontaneously. Synthesis is not the reverse of hydrolysis, explaining why high concentrations of free ATP does not inhibit synthesis. Gao and colleagues propose a detailed model of how the motor harnesses the proton gradient to act against the equilibrium. Their quantitative model is based on the conceptual “binding change mechanism” model proposed by Boyer, where ATP synthesis proceeds by each beta subunit changing from “open”, weak nucleotide binding, to “tight”, high affinity ATP binding, to “loose”, with the release of ATP. The authors used this model to make accurate predictions about synthesis and hydrolysis kinetics and they invite others to test their detailed model.
Yi Qin Gao, Wei Yang and Martin Karplus, "A Structure-Based Model for the Synthesis and Hydrolysis of ATP by F1-ATPase" Cell Oct 21, 2005; 123(2):195-205
Sunday, January 21, 2007
ATP Generator Structure – Function
at 9:49 PM
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