Past exam of the short options paper shared by Prelims and Parts A and B of the physics course of the University of Oxford / 2012 / S12 / 2

ATP synthase couples downhill proton motion across a cell membrane to synthesis of ATP from ADP and inorganic phosphate. Its membrane-embedded $F_o$ sector contains an $a$ subunit with offset proton-access half-channels and a rotating $c$-subunit ring. Reversible protonation of sites on the ring permits rotation relative to the stationary $a$ subunit. The central rotor transmits this motion through the $\gamma$ shaft to the soluble $F_1$ head. A peripheral stator holds the head relative to the membrane sector. The common bacterial schematic has an ${\alpha }_3{\beta }_3$ head, catalytic sites mainly on the three $\beta$ subunits, and a central $\gamma /ϵ$ rotor; accessory stator components depend on the organism.

The binding-change mechanism cycles the catalytic sites between open, loose-binding and tight-binding conformations. Rotor orientation changes their affinities for ADP, phosphate and ATP; the sites operate out of phase. Tight binding favors formation of bound ATP, and mechanical rotation changes the conformation to permit product release. In the ideal tightly coupled cycle, one revolution gives three catalytic turnovers:The proton count is not universally fixed: an ideal ring with $n_c$ proton-carrying subunits gives $n_c$ protons per revolution and $n_c/3$ protons per synthesized ATP, before additional transport costs.

For a proton moving from side 1 to side 2, its molar electrochemical potential change isThe chemical gradient and membrane electric potential difference together supply the proton-motive force. Synthesis requires the proton free-energy release to meet the positive Gibbs free energy of ATP synthesis. The coupling is reversible: isolated $F_1$ supplied with ATP can hydrolyse it and rotate its shaft, while the intact enzyme can use hydrolysis-driven rotation to pump protons against their gradient. The sketch is structural and schematic; it does not reconstruct the absent stepping trace.

Let $S_1(t)$ be the probability that an ATP-waiting state has not yet bound a substrate molecule. A constant bimolecular binding coefficient $k_1$ at fixed ATP concentration $c$ gives a pseudo-first-order hazard $\lambda =k_{1}c$. Thus ${\dot{S}}_1=-\lambda S_1$, $S_1(0)=1$, and the waiting-time distribution isThe probability density function starts at $k_{1}c$ and decreases exponentially. Increasing $c$ shortens the waiting time in inverse proportion. This supports one rate-limiting ATP-binding event before the associated motion, rather than a concentration-independent chemical delay.

For the second delay, consider sequential independent first-order transitions $A{⟶}^{k_a}B{⟶}^{k_b}C$. Their dwell times have exponential distributions. The total waiting time is their sum, so convolution givesIt is normalized, symmetric under exchange of $k_a,k_b$, and hasUnlike one exponential delay, it vanishes at $t=0$, rises initially as $k_a{k}_{b}t$, reaches a maximum at $t_{\mathrm{mode}}=\log (k_a/k_b)/(k_a-k_b)$ and eventually decays at the slower rate. For equal rates the continuous limit is $P_2(t)=k^{2}t{e}^{-kt}$, an Erlang distribution with mode $1/k$. If one rate is much faster than the other, the observed long-time behavior approaches one exponential. The sketch in the preceding section displays these shapes using arbitrary specified rates.

The simplest catalytic cycle compatible with the fits therefore contains an ATP-dependent binding delay and at least two resolvable ATP-concentration-independent kinetic events. Hydrolysis, product release and conformational changes are possible microscopic assignments, but the two-rate fit alone does not uniquely identify them or the order of $k_a$ and $k_b$. If each complete $120^{\circ }$ cycle contains these three waits and step durations are negligible, its mean duration is $(k_{1}c{)}^{-1}+k_a^{-1}+k_b^{-1}$ and the mean revolution rate is the inverse of three times this duration. Multiple catalytic sites can cooperate during that cycle.

TODO: the source PDF's stepping plot is absent. Its individual substep angles, numerical timings and the mapping of plotted dwell labels onto the larger or smaller angular movement cannot be read. The surviving text establishes only the $120^{\circ }$ total step and the existence of a larger and a smaller substep. No numerical rate, missing angle or plotted label is inferred from a different experiment. The distribution derivations and the concentration-dependence inference above are independent of that illustration.