Energetic Balance of the total oxidation of one mol of glucose up to CO2 and H2O: Understanding the contradictions.


 

For understanding the process of total oxidation of glucose, it is necessary to consider the different steps and metabolic pathways involved as well as the cellular location of these processes:

 

   

STEPS

M. PATHWAY

CELLULAR LOCATION

Glucose to  Pyruvate

Aerobic Glycolysis

Cytosol

Pyruvate to Acetyl CoA

Oxidative Decarboxylation of Pyruvate

Mitochondria

Acetyl Co A to CO2

Krebs Cycle

Mitochondria

  

 

Aerobic Glycolysis describes the oxidation of one mol of Glucose (6 carbons)  up to the formation of two moles of pyruvate (3 carbons each).

This conversion involves different reactions where ATP is produced or consumed:

Glucose to Glucose-6-(P)                                                                          – 1 ATP

 

Fructose-6-(P) to Fructose 1,6- bisphosphate                                 – 1 ATP

 

Since Fructose 1,6 bisphosphate becomes two trioses phosphate, the reactions after the aldolase reaction occurs twice (one for each triose that continues the glycolysis). In one reaction, NADH.H+  is produced; in other two reactions, a Substrate Level Phosphorylation (SLP) occur

 (2) Gliceraldehide 3 (P) to (2) 1,3 bisphosphoglycerate           +(2) NADH.H+

 

(2) 1,3 bisphosphoglycerate to (2) 3 phosphoglycerate (SLP*)     + 2 ATP

 

(2) Phosphoenol pyruvate to Pyruvate (SLP*)                                    + 2 ATP

 

(*Maybe it is necessary to recall now that there are two different ways of synthesizing ATP:  (a)SLP, in which ATP is synthesized using energy from some reactions of metabolism, like these reactions, and (b) Oxidative Phosphorylation, synthesis of ATP using the energy released in the Respiratory chain, from the oxidation of reduced cofactors)

 

Total energetic Balance from Glucose to (2) Pyruvate

(Aerobic Glycolysis): 

   _ 2 ATP  +  2 NADH.H+  + 4 ATP  = 2 ATP + 2 NADH.H+ in cytosol

 

 

An excellent animation of this process up to pyruvate can be found here.

 

Pyruvate will enter the mitochondria and will experiment Oxidative decarboxylation, in a reaction catalyzed by the pyruvate dehydrogenase complex.

The global reaction is:

2 Pyruvate + 2NAD+  +2 CoA —à 2 Acetyl CoA + 2 CO2 + 2 NADH.H+

This reaction occurs twice since each glucose (6 carbons) produce 2 pyruvates (3 carbons each), consequently these process produce

2 NADH.H+ in the mitochondria

 

Each Acetyl Co A is oxidized  in the Krebs Cycle yielding:

 

2 Isocitrate to 2 alfaketoglutarate            (+2CO2)                     2 NADH.H+

2 alfaketoglutarate to 2 Succinyl CoA (+2CO2)                          2 NADH.H+

2 Succinyl CoA to 2 Succinate (SLP)                                               2 GTP

2 Succinate to 2 Fumarate                                                                 2 FADH2

2 malate to 2 oxalacetate                                                                   2 NADH.H+

 

An animation with these reactions can be found in this link. 

Observe that at the end of the Kreb Cycle the 6 carbons of glucose have been oxidized to 6 CO2

 

At the same time, from the energetic point of view:

4 ATP have been obtained through Substrate level Phosphorylation (ATP synthesis without intervention of the energy of respiratory chain): 2 were obtained during the Aerobic Glycolysis and 2 were obtained in the Krebs Cycle as GTP (1 GTP is equivalent, from the energetic point of view,  to 1 ATP).

2 FADH2 have been obtained from the Krebs Cycle

8 NADH.H+ have been obtained inside the mitochondria (2 from Oxidative decarboxylation of Pyruvate and 6 from the Krebs cycle)

2 NADH.H+have been obtained in the cytosol through the Aerobic Glycolysis.

 

It is important to do these distinctions about the cellular location of the NADH.H+. since those produced in the cytosol should enter the mitochondria to be oxidized. Since the internal mitochondria membrane is impermeable to these nucleotides, (the mitochondria has their own pool of NAD) the NADH.H+ produced in the cytosol should enter using one of the shuttles already described for transporting the reduction equivalents of cytosolic NADH.H+  through the internal membrane of the mitochondria:

 

a)     the malate aspartate shuttle.

b)     The glycerophosphate shuttle

 

As described in other post, the malate-aspartate shuttle regenerates NADH.H+  inside the mitochondria, the energy yielding of the cytoplasmatic NADH.H+  is the same as if it was generated directly in the mitochondria

 

With the glycerophosphate shuttle, the reduction equivalents of the cytosolic NADH.H+  are transferred to FAD in the inner membrane. It means that the cofactor that will be oxidized in the respiratory chain when this shuttle is used, is FADH2 (see the explanation in this related post)

 

In conclusion, when the malate aspartate shuttle is used for transporting the reduction equivalents from the cytosolic NAD+ inside the mitochondria, we can consider that the t oxidation of glucose has produced:

4 ATP

10 NADH.H+  to be oxidized in the Respiratory chain

2 FADH2 to be oxidized in the Respiratory Chain.

 

If we use the convention that each NADHH+ produce approximately 3 ATP in the Respiratory chain, and each FADH2 produce 2 ATP, the total ATP production is:

 

Substrate Level Phosphorylation (SLP)                           04 ATP

10 NADH.H+  x 3 ATP/NADH.H                                          30 ATP

02 FADH2  x  2 ATP/FADH2                                                04 ATP

 Total                                                                                           38 ATP

 

Using the same convention (each NADHH+ produce approximately 3 ATP in the Respiratory chain, and each FADH2 produce 2 ATP,), but now assuming that the shuttle use is the glycerophosphate shuttle:

 

Substrate Level Phosphorylation (SLP)                         04 ATP

08 NADH.H+  x 3 ATP/NADH.H                                        24 ATP

04* FADH2  x  2 ATP/FADH2                                            04 ATP

 Total                                                                                         36 ATP

(*02 from the use of the glycerophosphate shuttle and 02 from the Krebs Cycle)

 

It explains that some textbooks say that the energetic Balance of the Total Oxidation a a mol of Glucose is 36-38 moles of ATP (since it depends on the shuttle that is used for entering the reduction equivalents of the NADH.H+ produced in the cytosol through glycolysis).

 

Other possible results:

 

As described in other post, some books use the convention that each mol of NADH.H+, when oxidized in the respiratory chain, produce approximately 2.5 moles of ATP, while each mol of FADH2 produce 1.5 moles of ATP. Using this convention:

When the malate-aspartate shuttle is used:

Substrate Level Phosphorylation (SLP)                         04 ATP

10 NADH.H+  x 2.5 ATP/NADH.H                                     25 ATP

02 FADH2  x  1.5 ATP/FADH2                                           03 ATP

 Total                                                                                         32 ATP

 

When the glycerophosphate shuttle is used:

Substrate Level Phosphorylation (SLP)                         04 ATP

08 NADH.H+  x 2.5 ATP/NADH.H                                    20 ATP

04* FADH2  x  1.5 ATP/FADH2                                        06 ATP

 Total                                                                                        30 ATP

(*02 from the use of the glycerophosphate shuttle and 02 from the Krebs Cycle)

 

It explains that some textbooks say that the energetic Balance of the Total Oxidation a a mol of Glucose is 30-32 moles of ATP

 

An advice: When solving a problem of this kind is absolutely necessary to know the conventions used for the yielding of the reduced cofactors (2.5 or 3 ATP/ NADH.H+ ? 1.5 or 2 ATP/ FADH2?) and the kind of shuttle that has been used for entering the reduction equivalents from the cytosol to the mitochondria.  A fair question will have both information. If not information is provided in the question, use the conventions followed by your professor during the lectures.

For students preparing for USMLE exams, the most used review books, like Harvey and Champe, in the “Lippincott Illustrated Reviews” of Biochemistry, Dawn B. Marks in “Biochemistry, Board Review Series”, Kaplan Biochemistry Lecture Notes for USMLE and “First Aid for the USMLE Step I”, agree in using the equivalence of  ‘approximately” 3 ATP for each NADH.H+  that is oxidized and ‘approximately” 2 ATP per FADH2. 

 

Related post:

To understand the mechanism of the shuttles and their difference in yielding ATP, I strongly recommend to read this post.

2 thoughts on “Energetic Balance of the total oxidation of one mol of glucose up to CO2 and H2O: Understanding the contradictions.

  1. Pingback: ATP yield in Aerobic Glycolysis: 5, 6, 7 or 8 ATP/glucose? « The Biochemistry Questions Site

  2. Pingback: Energetic Balance of the oxidation of 1 mol of Pyruvate up to CO2 and water « The Biochemistry Questions Site

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