Q: About a patient receiving Cholestyramine (LM-12)

 

 

Cholestyramine is used to reduce serum cholesterol because of its ability to interfere with the enterohepatic circulation of bile salts in the feces. When this drug is prescribed to a patient, which of the following compounds will be found in high concentrations in feces?

 

a) Doxycholate

 

b) Palmitate

 

c) Glucuronate

 

d) Bilirrubin

 

e) Squalen

 

f) estercobilinogen

Total Oxidation of a 17 carbon fatty acid, including oxidation of the resulting Propionyl CoA

Let’s use the basic calculations described in previous posts about this issue:

 

Beta-oxidation of  fatty acids with an odd number of carbons.

 

Energetic balance of the total (and I mean total) oxidation of a fatty acid with an odd number of carbons.

  

Oxidation of a fatty acid with 17 atoms of carbon.

 

 

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

 

Number of rounds in the Beta oxidation

(17/2) -1.5 = 8.5-1.5 = 7

7 rounds x  5 ATP/ round = 35 ATP

 

Number of units of Acetyl CoA produced = 7 Acetyl CoA

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

 

Propionyl CoA up to Succinyl CoA = -1ATP

 

Succinyl CoA up to Malate = 3 ATP

 

Malate up to Pyruvate (1 NADPH.H⁺)

 

Pyruvate up to Acetyl Co A = 3 ATP

 

Acetyl CoA oxidation in the Krebs Cycle = 12 ATP

 

Total of ATP (considering the total oxidation of Propionyl CoA converted to Malate and then from Malate to Pyruvate and then from Pyruvate to Acetyl CoA = -2 + 35 +84 -1 + 3 +3 +12 =  134 ATP

 

In summary  (following the equivalence of  1 NADH.H⁺ yielding 3 ATP in the Respiratory Chain and 1 FADH2 yielding 2 ATP):

 

-Calculate the number of rounds of the fatty acid in the Beta-oxidation:

  Number of rounds  = (Number of carbons/2) -1.5

 

-The number of Acetyl CoA is the same as the number of rounds

 

-Subtract 2 ATP that were used in the initial activation of the fatty acid.

 

-Multiply the number of rounds x 5 ATP/round.

 

-Multiply the number of Acetyl CoA x 12 ATP/Acetyl CoA.

 

-Add 17 ATP produced in the total oxidation of Propionyl CoA to CO2

 

 

To practice this kind of exercise, I suggest that you do the calculations using now  the criteria that considers that each NADH.H⁺ oxidized in the Respiratory Chain yields 2.5 ATP and each FADH2 yields 1.5 ATP

 

 

I am looking forward to see your answers and comments!!!

 

 

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)

 

C-C-C-C-C-C-C

 

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

 

C-C/C-C/C-C

 

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

 

C-C-C-C-C-C-C

 

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):

 

C-C-C/C-C/C-C

 

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.