title: Channelling free energy into work in biological processes.
abstract: The process by which free energy from ATP or an ion gradient is coupled to work--either osmotic work, by a membrane pump, or mechanical work, by a molecular motor--as well as the development of force by a molecular motor, can be explained by mechanisms dependent on substrate binding energy. Coupling involves a reaction sequence that combines the driving and driven reactions and that is controlled at switch points where the mobility of the coupling protein and its specificity in binding and catalysis can be abruptly altered; the altered state is an intermediate (or transition state) in the coupled reaction, the unaltered state an intermediate in the uncoupled reaction (slippage). The balance between these states, which is determined by the increase in substrate binding energy in the transformation, decides the relative importance of the coupled and uncoupled paths. On this basis a general expression for switching may be derived: the tightness of coupling is limited by a ratio of substrate dissociation constants before and after a controlling change in state: Rate(coupled)/Rate(uncoupled) < or = Kinitial state/Kfinal state. When binding energy is used in this way to distort the conformation of a protein, mechanical work is done; the work is internal but becomes external if the protein is connected to an external load. External work, force F multiplied by distance d, is then limited by a ratio of substrate dissociation constants before and after the conformational change: W = Fd < RT In(Kinitial state/Kfinal state). The ratios of dissociation constants, estimated from published values of the force exerted by molecular motors, are > 1 x 10(4) for myosin and > 2 x 10(4) for kinesin. From the tightness of coupling of the anion exchange carrier of red cells the ratio of constants for coupling is > or = 4 x 10(4). These increments can be accounted for by conversion of a surface complex to an enclosed complex, as in chelate formation. The work done by an ATP-driven motor is limited by the free energy of ATP hydrolysis, but the force developed is independent of the ATP reaction, and comes from binding energy with either the driving or driven substrate.
authors.affiliation: Agriculture Canada, London, Ontario, Canada. krupka@sscl.uwo.ca
authors.forename: R M
authors.initials: RM
authors.lastname: Krupka
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D001693:Biological Transport, Active / Q000502:physiology; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D002462:Cell Membrane / Q000378:metabolism; D004734:Energy Metabolism / Q000502:physiology; D008954:Models, Biological; D009124:Muscle Proteins / Q000502:physiology; D009132:Muscles / Q000502:physiology; D011485:Protein Binding; D011487:Protein Conformation; D013816:Thermodynamics
chemical_list: D002352:Carrier Proteins; D009124:Muscle Proteins; D000255:Adenosine Triphosphate