Many different compounds in the body can be broken down to yield ATP. There is almost always a question on the exam where you need to calculate the ATP yield of a certain compound. You must write the process of your calculation on the exam. Here are some examples of compounds:
- Fatty acids
- Hexanoate (hexanoyl-CoA without the -CoA)
- Octanoyl-CoA (an 8 carbon long fatty acid)
- Ketone bodies
- Glycolysis intermediates
- Glucose 1-phosphate
- Glucose 6-phosphate
- Fructose 1-phosphate
- Fructose 1,6-bisphosphate
To calculate the exact ATP yield you must know your MRTs, because you need to follow the pathway from the starting compound all the way until it’s broken down into NADH and FADH2. These electron carriers will enter the mitochondria and produce ATP by oxidative phosphorylation. One molecule of NADH yields 2,5 ATP and one molecule of FADH2 yields 1,5 ATP. You also need to know that each acetyl-CoA yields 10 ATP in the TCA cycle.
In the TCA cycle one acetyl-CoA yields 3 NADH, 1 FADH2 and 1 GTP. GTP is equivalent to ATP so we count it as an ATP. 3 x 2,5 + 1 x 1,5 + 1 = 10 ATP total.
ATP yield of glucose
Let’s start with the simplest. Glucose is metabolised through the glycolysis into 2 acetyl-CoA, which will then go through the TCA cycle.
Glucose is converted to glucose 6-phosphate. This requires 1 ATP, which we need to subtract from the total in the end. Glucose 6-phosphate is converted into fructose 6-phosphate, which doesn’t consume or produce ATP.
Fructose 6-phosphate is then converted into fructose 1,6-bisphosphate, which consumes another ATP. Currently we are at a yield of -2 ATP.
F1,6BP is then converted into glyceraldehyde 3-phosphate and dihydroxyacetonephosphate, the latter of which is converted into glyceraldehyde 3-phosphate. So now we have 2 glyceraldehyde 3-phosphate.
Each glyceraldehyde 3-phosphate is converted into 1,3-bisphosphoglycerate, each of which yields 1 NADH for a total of 2 NADH.
Each 1,3-bisphosphoglycerate is converted into 3-phosphoglycerate, which yields 1 ATP each for a total of 2 ATP.
Each 3-phosphoglycerate is converted into phosphoenolpyruvate.
Each PEP is then converted into pyruvate, which yields 1 ATP each.
Each pyruvate is converted to acetyl-CoA, which yields 1 NADH each.
Then, each acetyl-CoA enters the TCA cycle and yields 3 NADH, 1 FADH2 and 1 ATP each.
So, then we must add all together. We have 2 + 2 + 6 = 10 NADH, 2 FADH2 and -2 + 2 + 2 + 2 = 4 ATP. 10 NADH = 25 ATP and 2 FADH2 = 3 ATP.
4 ATP + 25 ATP + 3 ATP gives 32 ATP, which is the ATP yield of one molecule of glucose.
ATP yield of glycolysis intermediates
To calculate the ATP yield of other glycolysis intermediates just subtract those ATP and NADH which are produced or subtracted in the steps leading up to that intermediate.
For example, the ATP yield of glucose 6-phosphate is 32 – (-1) = 33 ATP, because glucose 6-phosphate doesn’t need to be phosphorylated and therefore doesn’t need the 1st ATP from above.
The ATP yield of fructose 1,6-bisphosphatase is 32 – (-2) = 34 ATP.
When considering the ATP yield of phosphoenolpyruvate it’s important to remember that only one molecule of acetyl-CoA is produced, in contrast to the breakdown of glucose. The ATP yield of PEP is 1 ATP + 1 NADH + 3 NADH + 1 FADH2 + 1 ATP = 1 + 1 x 2,5 + 3 x 2,5 + 1 x 1,5 + 1 = 13,5 ATP.
ATP yield of fatty acids
When considering the ATP yield of fatty acids it’s important to remember that for a fatty acid to enter beta oxidation a -CoA group must be attached to this fatty acid. This process (MRT 43) converts 1 ATP to 1 AMP, which is equal to consuming 2 ATP. In other words, the ATP yield of for example hexanoate is 2 ATP less than the yield of hexanoyl-CoA.
Beta-oxidation works in cycles. Each cycle of the beta-oxidation will make the fatty acid 2 carbons shorter, but it will yield 1 NADH, 1 FADH2 and 1 acetyl-CoA. Those 2 carbons the fatty acid lost are converted into acetyl-CoA. The fatty acid which is now 2 carbons shorter than the one we started with will enter the beta-oxidation, which will yield 1 NADH, 1 FADH2, 1 acetyl-CoA and a fatty acid which is 4 carbons shorter than the one we started with, and so on.
When the fatty acid is only 4 carbons long it will undergo its last round of beta-oxidation, and yield 1 NADH, 1 FADH2 and 2 acetyl-CoA.
This means that a fatty acid with 16 carbons can undergo 7 cycles of beta-oxidation, a fatty acid with 10 carbons can undergo 4 and so on.
Let’s do hexanoate as an example. The activation of hexanoate to hexanoyl-CoA requires 2 ATP, which we must keep in mind.
Beta-oxidation works in cycles. Hexanoyl-CoA will first undergo one cycle of beta-oxidation, which yields 1 NADH, 1 FADH2 and 1 acetyl-CoA, and the hexanoyl-CoA, which has lost 2 carbons, is now 4 carbons long and is therefore a butyryl-CoA.
Butyryl-CoA will undergo another cycle of beta-oxidation, yielding 1 NADH, 1 FADH2 and 2 acetyl-CoA.
In total we have 3 acetyl-CoA, each of which give 3 NADH, 1 FADH2 and 1 ATP. So the 3 acetyl-CoA give us 9 NADH, 3 FADH2 and 3 ATP.
We have undergone 2 beta-oxidation, each of which have yielded 1 NADH and 1 FADH2.
In total we have 9 NADH + 2 NADH = 11 NADH, 3 + 2 = 5 FADH2 and 3 ATP. This gives us 11 x 2,5 + 5 x 1,5 + 3 = 38 ATP. However, we mustn’t forget that we consumed 2 ATP when activating the fatty acid in the first place. So the total yield becomes 36 ATP.
ATP yields of ketone bodies
There are two ketone bodies which yield energy, acetoacetate and β-hydroxybutyrate. β-hydroxybutyrate is converted into acetoacetate by β-hydroxybutyrate dehydrogenase, which yields 1 NADH.
Acetoacetate is then converted into acetoacetyl-CoA by β-ketoacyl-CoA transferase, which doesn’t require energy. Acetoacetyl-CoA is then converted into 2 acetyl-CoA by thiolase.
In other words, the breakdown of β-hydroxybutyrate yields 1 NADH and 2 acetyl-CoA (= 22,5 ATP), while the breakdown of acetoacetate yields only 2 acetyl-CoA and no NADH (= 20 ATP).
If Berente decided to be extra difficult with your exam, you might be asked to calculate ATP yield of a compound WHILE there is arsenate poisoning.
Arsenate inhibits α-ketoglutarate dehydrogenase, glyceraldehyde 3-phosphate dehydrogenase and pyruvate dehydrogenase complex. This means that it inhibits the glycolysis at two points and the TCA cycle, severely hampering the ATP yield of everything. Arsenate is also very structurally similar to phosphate, so it can be incorporated into molecules instead of phosphate.
The only way to yield any ATP during arsenic poisoning is if ATP is yielded by other mechanisms (beta-oxidation or oxidation of β-hydroxybutyrate) or if the starting compound is, for example, PEP, which yields 1 ATP before being converted to pyruvate.
A question was asked on an exam, to calculate the ATP yield of fructose 1,6-bisphosphate during arsenate poisoning. Because arsenate inhibits glyceraldehyde 3-phosphate dehydrogenase, no ATP can be yielded from fructose 1,6-bisphosphate.
Enzymes and regulation
Hexokinase vs glucokinase