Question

I am testing the effects of a new drug, and find that liver cells treated with this drug show the following effects:

-Reduced levels of AcCoA in the mitochondria

-Increased rates of gluconeogenesis

-Increased production of lactate

The drug, however, has no effect on Red Blood Cells (RBCs).

Why does the drug not have an effect on Red Blood Cells? What is the drug inhibiting/assisting? What other conclusions can be made with this information? (Open ended question, there are no wrong answers!)

Answer 1

I believe that the new drug is an inhibitor of Pyruvate Dehydrogenase (PDH) enzyme which catalyses the conversion of pyruvate to acetyl CoA. It is a key enzyme in glucose metabolism connecting glycolysis with Krebs cycle.

Because the drug inhibits PDH, the production of acetyl CoA is hampered leading to the reduced levels of Acetyl CoA in the mitochondria. (Note: However, after certain period of time, cells will start producing Acetyl CoA from fatty acids to replenish ATP).

Because the drug inhibits PDH thereby Krebs cycle, cells lack enough ATPs for their use. So, the cells turn to increase gluconeogenesis to maintain basal glucose level. Gluconeogenesis creates glucose molecules from various precursors including pyruvate, intermediates of amino acid and lipid metabolism, etc.

Because the drug inhibits PDH, the pyruvate gets accumulated in the cell. This pyruvate, in turn, is converted to lactate via fermentation leading to the increased production of lactate.

The drug, however, has no effect on RBCs. This is because PDH is located in the mitochondria and RBCs lack mitochondria.