Enthalpy profiles for the hydride transfer, loop opening/closing, and pyruvate un/binding reaction steps without osmolytes, with 1 M TMAO, and with 1 M urea. The terms ‘OP’ and ‘CL’ refer to the loop open and closed geometries. Zero energy level is arbitrarily assigned to the lactate-side encounter complex (actually, this level must slightly differ for the three systems).