Question

In the glycolytic pathway, the enzyme triose phosphate isomerase catalyzes the conversion of of dihydroxyacetone phosphate to glyceraldehyde-3-phosphate, which is then immediately utilized by glyceraldehyde-3-phosphate hydrogenase to continue through glycolysis. In an experimental cell culture model, inhibition of triose phosphate isomerase leads to cell death in anaerobic conditions. These cells survive, however under aerobic conditions. Please explain these findings. In your answer consider the energy production in aerobic vs. anaerobic metabolism.

Answer 1

Under anaerobic conditions, glucose is converted to lactate or ethanol via fermentation pathway. Glycolysis produces two pyruvate molecules from glucose and also produces 1 NADH and 2 ATP. NADH is oxidized to NAD+ during fermentation and supports the continuous occurrence of glycolysis under anaerobic conditions. In aerobic conditions, NADH is oxidized by oxygen to produce NAD+.

One hexose molecule is cleaved to produce two pentoses i.e. G-3-P and DHAP. These two compounds are interconverted by triose phosphate isomerase (TPI). So, two trioses produce two ATP molecules via substrate level phosphorylation when TPI is functional. But, if TPI is mutated, only G-3-P can form one ATP molecule. This is not enough to support energy requirements of the cell under anaerobic conditions. Hence the cell will die.

However, DHAP can get back into oxidation pathway in the presence of oxygen. Hence, both DHAP and G-3-P can be utilized in the presence of oxygen even in TPI mutants.