Figure 1.

Schematics. (A) Simple ordered bi-bi model; the ${\overline{k}}_i$ values represent the apparent rate constants. (B) Theorell-Chance mechanism. (C) pH dependency of NADH oxidation proposed by Raval and Wolfe (29). (D) pH dependency of NAD reduction proposed by Raval and Wolfe (29). (E) Proposed pH model that assumes NAD/NADH binding to all enzyme-protonated states. (Dashed lines) Steps for which parameters are not identifiable. (F) Schematic of the proposed model, including multiple pH-dependent ionic states. In each of these schemes, A, B, P, and Q represent NAD, MAL, OAA, and NADH, respectively, and the substrate binding or product release is represented by the direction of the arrow. The diagram uses the convention of explicitly showing association steps for binding of forward-reaction substrates A and B, and dissociation steps for unbinding of products P and Q. In the reverse operation, for example in the step from EA to E in panel A, the reactant A dissociates, even though dissociation of A is not explicitly illustrated in the figure.