Question

Besides increasing the production of PDK enzyme, cancer cells increase production of lactate dehydrogenase (LDH). Why is the increase in LDH necessary?

Answer 1

Cancer cells show unregulated cell proliferation. Often they encounter hypoxic conditions. So, they have to activate anaerobic metabolic pathways. PDK is an enzyme that phosphorylates and inactivates pyruvate dehydrogenase (PDH). PDH is a key enzyme in aerobic metabolism that converts pyruvate to Acetyl CoA so that it can enter TCA cycle.

LDH also plays a major role in anaerobic respiration. It converts pyruvate to lactate and regenerates NAD+. In aerobic conditions, NADH is oxidized to NAD+ by ETC. However, ETC can not occur under hypoxic conditions. So, fermentation pathway regenerates NAD+ that is essential for the continuous occurrence of glycolysis.

Hence cancer cells upregulate LDH so that they can produce more ATP for its unregulated growth via fermentation.

Pyruvate + NADH + H+ ---------> Lactate + NAD+