Question

Phenformin is a drug that was once prescribed to treat type-2 diabetes. However, it was banned by the FDA because patients started presenting complications from lactic acidosis. If phenformin increased anaerobic metabolism, provide a rationale for lactic acidosis in phenformin treated patients. Your answer should include a metabolic pathway diagram in your rationale.

Answer 1

As phenformin increases anerobic metabolism, glycolysis is switched to its anerobic mode to recover its inducing equivalents. In which Pyruvate is converted to lactate with coupled regeneration of NAD+ which can further be used in glycolysis for ATP generation, as in anerobic mode the oxidative phosphorylation will also be impaired. And this increased lactic acid in the circulation is the cause of lactic acidosis. And in severe cases it can lead to death.