In a eukaryotic cell, the process of cellular respiration can metabolize one molecule of glucose into 30 to 32 ATP. Carbon dioxide (CO2) and water (H2O) molecules are produced as byproducts in these reactions.
Let’s do some accounting for single glucose molecule and calculate how we get the 30-32 ATP. Energy extraction from a glucose molecule happens in three metabolic pathways that we collectively term as cellular respiration. In the first two – glycolysis and citric acid cycle, most of the energy extracted is stored in NADH and FADH2. However, these two pathways still produce some ATP through a process known as substrate phosphorylation. Net 2 ATP is produced as glucose is decomposed to two pyruvic acid molecules in glycolysis. On the other hand, each citric acid cycle produces 1 ATP molecule. But, as we have two pyruvic acids entering into seperate citric acid cycles, totally 2 ATP is produced in citric acid cycles for one glucose molecule. Now, we have 4 ATP in our book.
The rest (26-28 ATP) is produced in oxidative phosphorylation as the energy in NADH and FADH2 is extracted. Based on a lot of experimental work, it appears that four hydrogen ions must flow back into the matrix through ATP synthase to power the synthesis of one ATP molecule. When electrons from NADH move through the transport chain, about 10 hydrogen ions are pumped from the matrix to the intermembrane space, so each NADH yields about 2.5 ATP. Electrons from FADH, which enter the chain at a later stage, drive pumping of only 6 hydrogen ions, leading to production of about 1.5 ATP.
With this information, we can do a little inventory for the breakdown of one molecule of glucose:
||Direct Products (Net)
||Ultimate ATP Yield (Net)
|Citric acid cycle
||30 – 32 ATP
The number of ATP molecules generated via the catabolism of glucose can vary substantially. If every single proton pumped in the electron transport chain as a result of electrons harvested from glucose went towards synthesizing ATP, 38 ATP would be synthesized. However, this doesn’t reflect what happens in a real cell. For example, the number of hydrogen ions the electron transport chain complexes can actually pump through the membrane varies between species. Another source of variance occurs during the shuttle of electrons across the membranes of the mitochondria. The NADH generated from glycolysis cannot easily enter mitochondria. Thus, electrons are picked up on the inside of mitochondria by either NAD+ or FAD+. These FAD+ molecules can transport fewer ions; consequently, fewer ATP molecules are generated when FAD+ acts as a carrier. NAD+ is used as the electron transporter in the liver, and FAD+ acts in the brain.
Another factor that affects the yield of ATP molecules generated from glucose is the fact that intermediate compounds in these pathways are used for other purposes. Glucose catabolism connects with the pathways that build or break down all other biochemical compounds in cells, but the result is not always ideal. For example, sugars other than glucose are fed into the glycolytic pathway for energy extraction. Moreover, the five-carbon sugars that form nucleic acids are made from intermediates in glycolysis. Certain nonessential amino acids can be made from intermediates of both glycolysis and the citric acid cycle. Lipids, such as cholesterol and triglycerides, are also made from intermediates in these pathways, and both amino acids and triglycerides are broken down for energy through these pathways. Overall, in living systems, these pathways of glucose catabolism extract about 34 percent of the energy contained in glucose.
MCAT Official Prep (AAMC)
Sample Test B/B Section Question 28
• While glucose catabolism always produces energy, the amount of energy (in terms of ATP equivalents) produced can vary, especially across different species.
• The number of hydrogen ions the electron transport chain complexes can pump through the membrane varies between species.
• NAD+ provides more ATP than FAD+ in the electron transport chain and can lead to variance in ATP production.
• The use of intermediates from glucose catabolism in other biosynthetic pathways, such as amino acid synthesis, can lower the yield of ATP.
Catabolism: Destructive metabolism, usually including the release of energy and breakdown of materials.
ATP synthase: A molecular machine that uses a proton (H+) gradient to form ATP from ADP and inorganic phosphate (Pi).
Oxidative phosphorylation: The final stage of cellular respiration where the combined action of the electron transport chain and chemiosmotic coupling result in ATP production.