Q22 - Metformin and Complex I

Theoretical 2 Real exam question - full text reproduced under IBO's CC BY-NC-SA 4.0 license

Bioenergetics & Central Metabolism Overview

In mitochondria, ATP is synthesized using an electron transport chain containing four complexes (I–IV) and ATP synthase (complex V). Three NADH and one FADH₂ molecules are produced by one turn of the Krebs cycle (citric acid cycle / TCA cycle).

The efficiency of ATP synthase varies between different cell types, but assume that the flow of about 3.3 protons allows the synthesis of one ATP molecule.

Metformin, which inhibits complex I, is used to treat type 2 diabetes. Metformin is believed to alter the usual cellular AMP:ADP:ATP ratio of 1:10:100, which produces a beneficial effect from AMP-activated protein kinase (AMPK).

Electron transport chain diagram showing Complexes I–IV, ATP synthase, and the site of metformin inhibition at Complex I

True or False?

Q22.1. The oxidation of one glucose molecule leads to the synthesis of approximately 11 ATP molecules.

Q22.2. The number of ATP molecules synthesized by ATP synthase is reduced by metformin.

Q22.3. Metformin directly increases the concentration of FADH2 in the mitochondrial matrix.

Q22.4. Metformin indirectly activates AMPK by raising the amount of AMP relative to ATP.

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Question reproduced from IBO 2023, Theoretical Paper 2, licensed under CC BY-NC-SA 4.0 - attributed to the International Biology Olympiad. Open the full exam PDF