Question

Show the three reactions in the citric acid cycle in which NADH is produced. Including the structures. None of these reactions involves molecular oxygen (O2), but all three reactions are strongly inhibited by anaerobic conditions. Explain why.

Answer 1

The reaction of citric acid cycle in which NADH is produced are :

1) In the first reaction, we see our first generation of NADH from NAD. The enzyme isocitrate dehydrogenase catalyzes the oxidation of the –OH group at the 4' position of isocitrate to yield an intermediate which then has a carbon dioxide molecule removed from it to yield alpha-ketoglutarate.

2)

In this reaction alpha-ketoglutarate loses a carbon dioxide molecule and coenzyme A is added in its place. The decarboxylation occurs with the help of NAD, which is converted to NADH. The enzyme that catalyzes this reaction is alpha-ketoglutarate dehydrogenase. The mechanism of this conversion is very similar to what occurs in the first few steps of pyruvate metabolism. The resulting molecule is called succinyl-CoA.

3)

In the final reaction of the citric acid cycle, we regenerate oxaloacetate by oxidizing L–malate with a molecule of NAD to produce NADH.

In the aerobic conditions the problem is that you can't reoxidize reduced coenzymes which are produced by TCA cycle in mitochondria. So the blockage comes from accumulation of NADH and FADH2. Also, If no oxygen is present, pyruvate (produced by glycolysis) is not allowed to enter the Krebs cycle and it is further oxidized to produce lactic acid.