Question

Its a biochemistry question

Consider the entire malate dehydrogenase mechanism. Please comment on the favorability of the forward reaction (estimate an approximate ΔG°’ and involve all components of this coupled reaction).

Answer 1

$images?q=tbn:ANd9GcQIT-3AKJ9GEmBon4TxoTD$ The reaction in a nutshell. It is a proton transfer reaction.

Now, The forward reaction in itself without the NAD reduction is not feasible.

Mechanism (http://www.chem.uwec.edu/Webpapers2000/Pages/Webpapers2000/freecr/pages/mechanism.html):-

First the proton is transferred from oxygen of malate to the nitrogen of the imidazole ring of the His-177 in the malate dehydrogenase (MDH). In a separate step, a hydride anion is transferred from the carbon of malate to the carbon of the nicotinamide ring of NAD to produce NADH. The initial step, the proton transfer, encounters an energy barrier of & kcal/mol and the next step, the hydride transfer, encounters an energy barrier of 15kcal/mol, which suggests the hydride transfer is the rate limiting step.

So, now pKa of imidazole of histidine ring is 6 and and pka of hydroxyl is 13. Now, by the formula (free energy = -2.303RT[pK_a(imidazole) - pK_a(hydroxyl)] ) = -2.303 * 2Cal/K *298 K * [(6-13)] = 9.6kcal/mol (Ans)