Some readers have asked about the oxidation of odd chain fatty acids.
Reviewing the subject, I found a lack of detailed information in the literature available on the Internet, and even in texts of Biochemistry that are frequently used in the Schools of Medicine and Biochemistry courses in other academic careers. This lack of information is the result of the fact that the bulk of fatty acids in our bodies, (and in the diet we consume) are generally fatty acids with an even number of carbons.
Referring to the oxidation of odd-chain fatty acids, texts and articles usually are limited to report that in the last round of the Beta-oxidation of fatty acids of this type, one Propionyl CoA and one Acetyl CoA are produced, and then these texts generally describe the conversion of Propionyl CoA to Succinyl CoA, but without specifically mentioning the ATP balance in these reactions.
Therefore, and answering your questions, I have included in this post the energetic considerations to take into account when analyzing the ATP production in the oxidation of fatty acids of an odd number of carbons:
N= number of carbons
(N/2) –1.5 = Number of rounds in the Beta-oxidation
(N/2) –1.5 = Number of acetyl CoA produced in the Beta-oxidation
Additionally, 1 Propionyl CoA (3-carbon Acyl CoA) is produced in the last round.
Based on a yield of 3 ATP per NADH.H+ and 2 ATP per FADH2 that are oxidized in the respiratory chain:
-Multiply the number of turns in Beta-oxidation x 5 ATP / turn
–Multiply the number of Acetyl CoA x 12 ATP / Acetyl CoA (since each Acetyl CoA yields 12 ATP when oxidized in the Krebs Cycle)
–Subtract now two ATP (-2 ATP) consumed in the initial activation of the fatty acid (see the related post for explanation)
But also, in this process, as was written before, 1 Propionyl CoA is released, because in the last round of the Beta-oxidation, instead of obtaining two Acetyl CoA (as with the even chain fatty acids), the odd fatty acids now yields 1 Acetyl CoA and 1 Propionyl CoA.
What happens with this Propionyl CoA?
The Propionyl CoA must undergo a carboxylation in a sequence of reactions requiring Biotin and Vitamin B12. These reactions produce Succinyl CoA.
Note also that this sequence of reaction requires the consumption of 1 ATP (then consider it as -1 ATP )
What happens to the carbon atoms of the Succinyl CoA?
Let’s discuss an anaplerotic fate for the Succinyl CoA:
We can consider the conversion of propionyl CoA to Succinyl CoA as an anaplerotic pathway, in which case, the molecule of Succinyl CoA continue in the Krebs Cycle generating Oxalacetate in the following sequence of reactions:
Succinyl CoA + GDP + (P) —> Succinate + CoA + GTP (equivalent to 1 ATP)
Succinate + FAD ———-> Fumarate + FADH2 (Generates 2 ATP in the Respiratory Chain)
Fumarate + H2O————– > Malate
Malate + NAD+ —————-> Oxalacetate + NADH.H+ (Generates 3 ATP in the Respiratory Chain)
Remember that by definition the products of the anaplerotic reactions are incorporated into the Krebs Cycle, increasing its activity, but without being oxidized. In this case, because of the sequence of reactions experienced by the Succinyl CoA up to Oxalacetate, we can consider that the incorporation of the Succinyl CoA originated from the Propionyl CoA, has generated 6 additional ATPs.
Therefore, considering the “anaplerotic” fate of the Propionyl CoA:
– Add (-1 +1 +2 +3) = 5 ATP to the previous calculations.
In our next post, we will use an example. We will apply this information in the calculation of the energetic balance of the Beta-oxidation of the decaheptanoic acid (17 Carbons), assuming that the propionyl CoA has followed the anaplerotic pathway up to oxalacetate, as described in this post.