Question

why is step 8 (dehydrogenation) of the citric acid cycle regulated? in other words why is malate dehydrogenase regulated?

plz explain with detalis and give me a definite answer why that step is being regulated

Answer 1

in the last reaction of the citric acid cycle, NAD linked L-malate dehydrogenase catalyzes the oxidation of L-malate to oxaloacetate.

L-malate + NAD+ ---> oxaloacetate + NADH + H+

the equilibrium of this reaction lies far to the left under standard thermodynamic conditions, but in intact cells oxaloacetate is continually removed by the highly exergonic citrate synthase reaction. this keeps the concentration of oxaloacetate in the cell extremely low( < 10^-6 M) , pulling the malate dehydrogenase reaction toward the formation of oxaloacetate.

three factors govern the rate of flux through the cycle; substrate availability , inhibition by accumulating products and allosteric feedback inhibition of the enzymes that catalyze early steps in the cycle.

in the cell, the malate dehydrogenase reaction is essentially at equilibrium(that is , it is substrate limited) , and when [NADH]/[NAD+] is high , the concentration of oxaloacetate is low, slowing the first step in the cycle. product accumulation inhibits the rate limiting step of the citric acid cycle.

malate aspartate shuttle for transporting NADH from cytosol into the mitochondrial matrix. NADH in the cytosol transfers electrons to oxaloacetate, producing malate. malate is transported across the inner membrane by the help of transporter. in the matrix , malate passes electrons to NAD+ ; the resulting matrix NADH is finally oxidized by the mitochondrial respiratory chain.