What does "thermodynamic equilibrium" mean for an enzyme-substrate complex? From Fersht, Enzyme Structure and Mechanism p. 87: > The Michaelis-Menten mechanism assumes that the enzyme-substrate complex is in thermodynamic equilibrium with free enzyme and substrate. In my understanding what this means is that the (E-, S- and ES-concentration dependent) rates of association and dissociation have equated. So we're kind of in this situation: !enter image description here where "product" would be referring to [ES] and "reactant" to [E] and [S]. Does that make sense?

Thermodynamic equilibrium means that:

Rate of forward reaction = Rate of backward reaction

In this case:

$E + S\xrightleftharpoons[k2]{k1} ES\\\ \ \\\ \ \\\ \\\ at\ equilibrium:\\\ \ \ \\\ \ k1.[E][S] \tiny{\ (forward\ rate)}\
ormalsize= k2.[ES] \tiny\ (backward\ rate) $

This was the initial assumption in the Michaelis-Menten model.

Later on this was improvised by assuming **pseudo-steady state** of ES complex. This means that $[ES]$ does not change over time, which is both as a result of its production by the reversible reaction: $E + S \leftrightharpoons\ ES$ and consumption by the irreversible reaction $\ ES\ \xrightarrow{k3} E+P$

that is:

$k1[E][S]\tiny\ (production)\
ormalsize=(k2+k3)[ES]\tiny\ (consumption)$