6.5 The ATP yield of oxidative glucose degradation

We can now determine how much ATP is gained through the complete degradation of glucose via glycolysis, TCA, and respiratory chain. Here are the bits and pieces:

4 moles of NADH are produced in glycolysis (by glyceraldehyde-3-phosphate dehydrogenase) and by pyruvate dehydrogenase;
6 moles of NADH and 2 moles of FAD are produced in the TCA;
10 protons exported per NADH + 6 protons per FAD → 112 protons total;
Each revolution of ATP synthase allows 10 protons back into the mitochondrion → one molecule of glucose drives 11.2 revolutions of ATP synthase;
Each revolution of ATP synthase makes 3 ATP.

Therefore, 33.6 ATP could be generated by oxidative phosphorylation per molecule of glucose degraded, if all protons were available for driving ATP synthase. However, some protons are diverted to other purposes, so that the actual yield will be lower than the theoretical value. Most importantly, some protons are needed for ATP transport: ATP synthesized in the mitochondrion needs to be exported to the cytosol, and ADP needs to get back in. This is accomplished by a special transporter protein in the inner mitochondrial membrane that exchanges ATP and ADP for each other. Since ATP carries one more negative charge than ADP (ATP^4- vs. ADP^3-), this exchange amounts to a net export of one negative charge, or to the net import of one positive charge¹ per ATP. The total need of protons per ATP—synthesis plus export to the cytosol—is therefore approximately 4, so that the actual ATP/glucose ratio is closer to 28 than to 33. Together with the 4 ATP and GTP molecules generated in glycolysis and the TCA, the overall yield of ATP per molecule of glucose is approximately 32.

It is worth noting that the extra proton expended on the export of ATP is not 'wasted' (as some textbooks are fond of lamenting) but can be considered well spent. It allows the transport of ATP and ADP against their concentration gradients, allowing for the maintenance of a high ATP/ADP ratio in the cytosol, which will help all ATP-consuming reactions there to go at speed, and a higher ADP/ATP ratio in the mitochondrion, which will help the ATP synthase to go at speed. It is kind of like driving on the highway—sure, you could save fuel by driving at 60 km/h all the time, but would you?

1: It is not actually a proton—so, in my understanding, it is only the membane potential component but not the proton concentration component of the proton-motive force that gets dissipated. Then, it costs about 3/4 of the energy of a pumped proton to export one ATP.