Question

Propionate is commonly used as an inhibitor of microbial growth. This growth inhibition comes from propionate being converted into propionyl-CoA (shown below) and then entering the TCA cycle. Explain why this results in growth inhibition.

Answer 1

Propionate is acted upon by the CoA Synthetase to be converted to Propionyl CoA. This Propionyl CoA enters a modified TCA called called the methylcitrate cycle.

The Propionyl-CoA, however, competes with Acetyl-CoA to get bound to Pyruvate dehydrogenase. As a result, the propionyl-CoA undergoes metabolism at the expense of preventing Acetyl-CoA from entering the classical TCA cycle. The accumulation of Acetyl-CoA in the cell leads to inhibition of CoA Synthetase, which in turn leads to accumulation of Pyruvate. Thus, the pH of the cell starts getting acidified. This acidification further leads to metabolic blockage as the concentration gradient necessary to drive the ATP Synthetase pump is hindered. Eventually, cell becomes metabolically unstable and the growth is inhibited.