Question

The antidiabetes drug metformin inhibits 3-phosphoglycerol dehydrogenase. How would this affect ATP production by mitochondria?

Short answer

The drug will decrease the synthesis of ATP in mitochondria.

Step-by-step solution

Enzyme 3-phosphoglycerol dehydrogenase

Glycerol-3-phosphate dehydrogenase or 3-phosphoglycerol) catalyzes the conversion of dihydroxyacetone phosphate (DHAP) to glycerol-3-phosphate.

Glycerol-3-phosphate shuttle

In yeast, plants, and animals, the glycerol-3-phosphate (G-3-P) shuttle is a critical mechanism for transporting cytosolic reducing equivalents into mitochondrial oxidative phosphorylation. The glycerol-3-phosphate shuttle allows NADH (produced in the cytoplasm during glycolysis) to contribute to the oxidative phosphorylation pathway (in the mitochondria) to produce ATP.

Effect of metformin

The synthesis of ATP in mitochondria would be reduced if metformin inhibited 3-phosphoglycerol dehydrogenase as the conversion of dihydroxyacetone phosphate (DHAP) to glycerol-3-phosphate is inhibited that shuttles NADH from cytoplasm to mitochondria for oxidative phosphorylation.