Energetic Balance of the Total (and I mean Total) Oxidation of a Fatty Acid with an Odd number of Carbons.

In previous posts we have discussed how the fatty acids with an odd number of carbons chain, release 1 unit of Acetyl CoA and 1 unit of Propionyl CoA, instead of the two Acetyl CoA units released when a fatty acid with an even number of carbons is beta-oxidized.


Let’s use some examples, (we represent here just the carbons in the chains):


Example 1: a fatty acid with 6 carbons (Hexanoic acid)




During the Beta-oxidation, three units of Acetyl CoA are released (two carbons each):




Example 2: A fatty acid with 7 carbons (Heptanoic acid):




During the Beta-oxidation two units of Acetyl CoA and one unit of Propionyl CoA are released (two units of two carbons and one unit of three carbons):




As discussed previously in another post, the Acetyl CoA are oxidized in the Krebs Cycle, but the Propionyl CoA is used in the formation of Succinyl CoA, in a process that consumes 1 ATP (-1 ATP).


The Succinyl CoA can continue in the Krebs Cycle and form Oxalacetate. Oxalacetate will react with Acetyl CoA (Citrate Synthase reaction) to form Citrate, following the reactions in the Krebs Cycle. If it happens, we can consider that the atoms of carbons of the Propionyl CoA have followed an anaplerotic pathway (to be used in the Kreb’s Cycle without being consumed). 


BUT these carbons could also be completely oxidized if they follow this sequence of reactions:


Succinyl CoA + GDP + (P) – -> Succinate + CoA + GTP (it is equivalent to 1 ATP)


Succinate + FAD – – – – >Fumarate + FADH2 (It generates 2 ATP in the Respiratory Chain)


Fumarate + H2O—–> Malate


But the Malate can now diffuse from the matrix through the mitochondrial membranes and be decarboxylated (under the action of the cytoplasmatic malic enzyme) to Pyruvate (and production of 1 CO2).


Pyruvate can return to the interior of the mitochondria,  where another decarboxylation occurs, this time under the action of the  Pyruvate dehydrogenase complex, (with production of another CO2) and the formation of Acetyl CoA, whose Acetyl group will be oxidized in the Cycle producing other two molecules of CO2.


We can see that through this sequence of reactions it is possible the total oxidation of the three original carbons of the Propionate to 3 molecules of CO2! (To avoid confusions, observe that, yes, there are 4 decarboxylations, but one of the CO2 does not come originally from the Propionyl CoA, but from the carboxylation process in the conversion of Propionyl CoA to Succinyl CoA)


Which would be the energetic balance of the total oxidation of an odd chain fatty acid considering this sequence of reactions?


Let’s see:


Propionyl CoA to Succinyl Co A = -1 ATP


In the mitochondria, (following the reactions of the Kreb’s Cycle up to Malate):


Succinyl CoA + GDP + (P) –> Succinate +CoA + GTP (it is equivalent to 1 ATP)


Succinate + FAD ——– – – – > Fumarate + FADH2 (It generates 2 ATP in the Respiratory Chain)


Fumarate + H2O————–>Malate


In the cytoplasm:


Malate + NADP+ – – – >Pyruvate + NADPH.H+ + CO2 (we will not consider this  reduced cofactor in the balance since NADPH.H+ is not a source of energy, but a source of reduction equivalents for synthetic reactions)


In the mitochondria again:


Pyruvate + CoA + NAD+ —-> Acetyl CoA + CO2 + NADH.H+ (Observe that this NADH.H+ is generated inside the mitochondria, so it yields 3 ATP)


The Acetyl CoA produced in the previous reaction, when oxidized in the Krebs Cycle: 12 ATP


Therefore, considering this metabolic way,


-1 +1 +2 +3 + 12 = 17 ATP as a result of  the total oxidation of the Propionyl CoA generated by the beta-oxidation of a fatty acid of odd number of carbons.



Therefore, for calculating the energetic balance we should add 17 ATPs from the oxidation of the Propionyl CoA, to the ATPs generated in the Beta-oxidation, and the ATPs generated as a result of the oxidation in the Krebs Cycle  of the Acetyl CoA units formed during the Beta-oxidation of the odd chain fatty acid. ( We should recall also that 2 ATPs are consumed in the initial activation of the fatty acid)


In our next post we will analyze the oxidation of the heptadecanoic acid (17 carbons) as an example of the application of these calculations.


Oxidation of a fatty acid with 17 atoms of carbon

(This post analise the energetic balance considering that the Propionyl CoA follows an anaplerotic fate)


Apply the equations described in the previous post:


N= Number of Carbons


(N/2) -1.5 = Number of rounds in Beta-oxidation


(N/2) -1.5 = Number of acetyl CoA produced in Beta-oxidation


So, in terms of production and consumption of ATP of ATPs, the oxidation of a 17-carbons fatty acid will show the following energetic balance:


Activation of a fatty acid to Acyl CoA = -2 ATP


Number of rounds in Beta-Oxidation:


(17/2) – 1.5 = 8.5 -1.5 = 7

7 rounds x 5 ATP/round = 35 ATP


Number of produced Acetyl CoA: 7 Acetyl CoA


7 Acetyl CoA x 12 ATP/Acetyl CoA = 84 ATP


Additionally, the Beta-oxidation has produced 1 Propionyl CoA. The conversion of Propionyl CoA to Succinyl CoA, as described in a former post, will consume 1 ATP (Consider -1 ATP).


As described in a previous post:


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 ATPs in the Respiratory Chain)


Fumarate +     H2O————– > Malate


Malate +   NAD+ —————->  Oxalacetate + NADH.H+ (Generates 3 ATPs in the Respiratory Chain) “


Total = (-1+1+2+3) = 5 ATPs


Total of ATPs produced (considering the anaplerotic fate of the Propionyl CoA turned into Succinyl CoA) = -2+35+84-1+6 = 122 ATP                        




We may also consider a total oxidation that would include the carbon atoms of the Propionyl CoA!


In our next post, we will consider what happens if, instead of the Succinyl CoA following an anaplerotic pathway, it follows a path that allow the carbon atoms of Propionyl CoA end up being oxidized to CO2. It would allow a real  total oxidation of all the original carbons of the heptadecanoic acid or any other fatty acid with an odd number of carbons.



Oxidation of fatty acids with an odd number of carbons


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.



Biochemistry Question CM-22


A 15 year-old patient complains of painful muscle cramps when performing physical exercise, followed by stiffness and weakness, and excretion of wined colored urine. A muscle biopsy indicates a muscle glycogen concentration much higher than normal. Deficit of which of the following enzymes is most likely causing these problems in this patient?


a) Creatin kinase


b) ATP synthase


c) Glycogen phosphorylase


d) Glycogen synthase


e) Glucose 6 phosphatase


Cataracts and Biochemistry of the Lens


Original questions:






The light should pass through the cornea, aqueous humor, lens and vitreous humor before reaching the retina for triggering the process of vision. These structures should be transparent in order to allow the path of light.



The lens (m in the figure) is bathed in its anterior side by the aqueous humor (i) and in its posterior side by the vitreous humor (o). It has no blood capillaries (that would interfere with light path), so the aqueous humor is responsible of the nutrition of the lens and the disposal of metabolic products.


The energy necessary for the lens is provided mainly through anaerobic glicolysis; the Krebs cycle, located in peripheral cells, only provide about 5 % of the necessary energy. Pentose phosphate cycle is also another important metabolic pathway in lens since it provides NADPH necessary for the maintenance of the redox status of the lens proteins.


The majority of the proteins in the lens are alpha, beta and gamma crystallines. They should maintain a transparent environment, so they should be in a native, non aggregate state. Some disturbances, as changes in the redox states of these proteins or changes in osmolarity in the lens can produce lost of the native state and aggregation of these proteins.


Cataracts results from changes in solubility and aggregation of the crystallin proteins.

The most frequent kinds of cataracts are those that appear as result of aging (senile cataracts) or as a result of Diabetes Mellitus (diabetic cataracts). Other conditions can also result in cataracts: cataracts that appear in galactosemia are very similar in the way of production to the cataracts that appear in Diabetes.


Aldose reductase is an enzyme that usually reduce aldehyde group of aldoses to a primary alcohol, so the aldose becomes a polyalcohol. The enzyme uses NADPH as hydrogen donor.


Typical reactions catalyzed by aldose reductase are the formation of sorbitol (glucitol) and the formation of dulcitol (galactitol):


Glucose +NADPH —à Glucitol (Sorbitol) + NADP+


Galactose +NADPH —à Galactitol (Dulcitol) + NADP+

Sorbitol (Glucitol)

Sorbitol (Glucitol)



Aldehyde reductase function is mainly in the conversion of glucose to fructose.

Dulcitol (Galactitol)

Dulcitol (Galactitol)





The sequence of reactions is:


1. – Reaction of Aldehyde reductase:

Consist in the reduction of the aldehyde group of glucose to a primary alcohol group, with the conversion of the aldohexose glucose to a polyalcohol.


Glucose + NADPH.H+ —à Sorbitol + NADP+


2. – Reaction of Sorbitol dehydrogenase (SORD):

      Consist in the oxidation of the secondary alcohol group of Carbon 2 of Sorbitol to

       a ketone group. It results in the conversion of Sorbitol in Fructose, a ketohexose.


      Sorbitol + NAD+ –à Fructose + NADH.H+


This sequence of reactions is particularly important in the formation of fructose in the seminal vesicles and the liver, and it has the advantage over the use of the sequence in glycolysis for obtaining fructose – Glucose 6 (P) to Fructose 6 (P) – that this polyalcohol pathway does not require the expending of ATP.


Lens contains aldehyde reductase and also a very low activity of sorbitol dehydrogenase, so some of the glucose that enter in the lens is converted in fructose. This quantity is usually very low since the enzyme aldehyde reductase has a very high Km for glucose.


In conditions of hyperglycemia, since the concentration of aldehyde reductase substrate (glucose) is high, this enzyme becomes very active, and a high quantity of sorbitol is formed. Unfortunately for diabetic patients, the activity of sorbitol dehydrogenase in lens is very low (enough for normal conditions, but not for this abnormal situation) and for complicating more the problem, sorbitol formed in the lens diffuse with difficulty out of it.


As a result, Sorbitol accumulates and increases the osmotic effects producing cell swelling and structural damage (this effect would explain also the neuropathy and vascular problems present in Diabetic patients).


In the lens, these changes in osmolarity will affect the native conformation of the crystalline proteins, in such a way that they aggregate and form structures that scatter the light: Cataracts are being formed.


In patients with galactosemia, a congenital disease in which the patient can not metabolize galactose and this sugar accumulates, the physiopathology of cataracts formation and nerve damage apparently is similar to the mechanism described for diabetes:


Through the reaction of Aldehyde reductase occurs the reduction of the aldehyde group of galactose to a primary alcohol group, with the conversion of the aldohexose galactose to its corresponding polyalcohol, galactitol:


Galactose + NADPH.H+ —à Galactitol + NADP+


Galactitol accumulates increasing the osmotic pressure with similar results to those found in sorbitol accumulation in Diabetes Mellitus.



For more information, please visit the following links:


About Cataracts


Sorbitol: A hazard to diabetes


About side effects of Sorbitol


About Polyol pathway and arterioral dysfunction in hyperglicemia


About galactitol and cataracts formation in galactosemia