Multistep metabolic pathway/citric acid cycle

Question

Consider the following reactions, which are two consecutive steps in

the cyclic, multistep metabolic pathway known as the citric acid cycle.

The first reaction, which is not thermodynamically spontaneous, immediately precedes the second reaction, which will occur spontaneously. The two reactions are catalyzed by two independent

enzymes.

ΔG°(kJ/mol)

L-malate NAD --> oxaloacetate NADH H 7

acetyl-CoA oxaloacetate --> citrate CoA H -8

How can the initial reaction occur in this pathway with such a high positive free energy change?

a) this reaction must be coupled to ATP hydrolysis to occur

b) this reaction must be coupled to some external energy source to occur

c) the second reaction, which is thermodynamically spontaneous,

uses the oxaloacetate from the previous reaction and in effect,

"pulls" the first reaction along

d) the equilibrium constant for the initial reaction, although quite

small, is sufficient for the reaction to proceed

Answer 1

The best answer is C   the second reaction , citrate synthase, condenses OAA with acetyl CoA to make citrate and has a large - delta G. Importantly though is that citrate synthase MUST bind to OAA first to even expose the binding site for acetyl CoA. Thus the large -delta G reaction is dependent on OAA to drive it.Thus small amounts of OAA are sufficient to "activate " citrate synthase ( a small Km for the enzyme ).