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Oxidation of nutrients reduces ADP (adenosine diphosphate) to ATP (adenosine triphosphate). You may have heard your biology textbook or a doctor refer to ATP as the “energy currency of the cell.” And that is an adequate explanation. Your body needs ATP to move ions in adverse gradients (“uphill”), tense muscles, move, etc. If a human body goes one second without ATP, it dies. In fact, cyanide works by hijacking one step in the process of production of ATP. The most common way of manufacturing ATP in the human body is aerobic respiration, which we will go over in this article. The other two ways are lactic acid fermentation and the creatine kinase system, which will be the subjects of future posts.
The Citric Acid Cycle
In terms of energy, for the most part, the major macronutrients become a molecule called acetyl-CoA (acetyl coenzyme A). (There are other uses for all of them, to be discussed in their individual posts, but here we are just talking about oxidizing them into energy.) That acetyl-CoA can be used by every cell of the body. It is imported into the mitochondrion, where it takes part in the citric acid cycle (above). The citric acid cycle takes one molecule of acetyl-CoA, along with oxaloacetate, and converts three NAD+ ions into NADH and one ADP (or GDP) into ATP (GTP). It produces two waste CO2 molecules and also hydrolyzes some other molecules. (The exact molecules vary on what specifically is going on at the cell.)
There are a few important things to note about the citric acid cycle: It is a cycle. At the end, the cell ends up with one oxaloacetate molecule that can then oxidize another acetyl-CoA. The above diagram is a simplification. All of this is happening in solution so these molecules end up interacting with each other. Sometimes, if a certain substrate is needed, the cycle doesn’t continue to completion. Sometimes, the cell ends up with too much citrate, and the cell can then break down citric acid into acetyl-CoA and feed into its own cycle! Furthermore, the cell looks at concentrations of various substrates to determine what else it needs to do.
The cell can use ATP directly for energy. But the citric acid cycle only produces one ATP per cycle. NADH enters the electron transport chain to make much more ATP.
The Electron Transport Chain
The mitochondrion has an outer membrane and also smaller membranes inside of it that enclose its matrices. Between those, there are several ion pumps. Across any membrane, if there is a charge gradient, the there is energy bound up in that gradient. For instance (looking at the diagram above), if there are more positive charges outside of the inner membrane than inside, then it will take energy to deposit even more ions outside. However, if the cell were to take those positive ions into the membrane, the it would actually gain energy from this transaction.
The standard metaphor for charge gradients is a ball rolling downhill. At the top of the hill, it has potential energy, and when it rolls downhill it gains energy. Theoretically you could use that energy to power something else. Well the cell does this many trillions of times a day, harnessing the energy from moving the ions to a lower energy state. Similarly, “pumping” ions to a higher energy state takes energy just like rolling a ball up the hill.
The electron transport chain can take the chemical energy from one NADH and and convert it to electric potential by rolling six hydrogen ions uphill (outside of the inner membrane, into the “inter-membrane space”). Then two hydrogens rolled uphill can be converted one ADP to ATP when ATP synthase rolls them downhill. Thus one NADH makes at most 3 ATP from ADP. (And a NAD+ ion is created which can feed back into the citric acid cycle as long as there is sufficient acetyl-CoA.)
The total ATP output of one molecule of glucose is about 30-34 ATP. About 22 of those ATP come from the citric acid cycle and electronic transport chain (also called oxidative phosphorylation).
These two processes are where the body obtains the vast majority of its energy, and approximately 60% of the chemical energy from the oxidation of nutrients actually goes to heat so that the human body can maintain its body temperature.1 These processes are extremely important, but they are just the endpoint. Carbohydrates, proteins, and fats all end up here (if they are being used as energy), even ketone bodies and alcohol just feed into this cycle at the end of the day. What’s interesting is what happens before the citric acid cycle in the body.
- 1. Looking at the “delta G” (change in Gibb’s free energy) of the reactions involved sheds light on how much energy is used and how much goes to heat. I don’t see the point of going into delta G at this point, but to put it succinctly, it is the energy released or used by a chemcial reaction. (A negative sign means that energy is released.) The total oxidation of glucose has a Delta G of about -2823 kJ/mol. The conversion of ATP to ADP has a delta G of about -34 kJ/mol. So if 34 moles of ATP is made from one mole of glucose, then the energy bound up in those ATP is about -34 kJ/mol × 34 mol = -1156 kJ, which is about 40% of -2823 kJ. The rest of the energy must have gone somewhere: It is heat. Recent evidence suggests that in the conditions of the human body the ATP to ADP reaction could be much more exergonic, perhaps about -64 kJ/mol. This could lead to up to 80% use of the energy of glucose.