Net Gain ATP In Aerobic Glycolysis? Theories, Possibilities, and Paradoxes Explained ...

Net Gain ATP In Aerobic Glycolysis?

Theories, Possibilities, and Paradoxes Explained ...

           Sometimes students get very confused when they found that the energetic balance in his Biochemistry book does not agree with the energetic balance studied in classroom. The student can get even more confused when he/she uses some consultation books and found that values also can differ from one book to another.

The intention of this post is to clear the apparent contradictions in energetic balance of the oxidation of glucose, in some of the books more used by biomedical students.

Aerobic Glycolysis describes the oxidation of one mol of Glucose (6 carbons)  up to the formation of two moles of pyruvate (3 carbons each). [Contrast with anerobic glycolysis]

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

1. Glucose to Glucose-6-P                                                                              – 1 ATP

1.  Fructose-6-P to Fructose 1,6- bisphosphate                                     – 1 ATP

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

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

1.   Phosphoenol pyruvate to Pyruvate (SLP)                                           + 2 ATP                                              

So, up to this moment it has been obtained in the aerobic glycolysis 2 ATP (through SLP) and 2 NADH.H+. This NADH.H+ will release energy for the synthesis of ATP in the Respiratory Chain…. but exactly how much ATP can be synthesized from the oxidation of this NADH.H+ ?

It is a question kind of complicated, since there are different factors affecting the answer:

1.- Which “energetic yield” criteria is used?

Traditionally Biochemistry textbooks have used the criteria that with the energy released by each mol of NADH.H+ that is oxidized in the Respiratory Chain, 3 moles of ATP can be produced. More accurate calculations indicates that in fact, the energy released when 1 mol of NADH.H+  is oxidized, is just enough for the synthesis of 2.5 moles of  ATP and not 3 ATP as considered before. Those calculations indicate also that the equivalent of the oxidation of 1 “mol” of FADH2 is enough for the synthesis of 1.5 moles of ATP and not 2 moles of ATP as was considered before. Anyway,  different textbooks continue using the equivalents of 3 and 2 ATP for eachNADH.H+  and FADH2 oxidized.

Besides this factor that affects all the calculations that involve the production of ATP from the oxidation of NADH.H+  or reduced flavoproteins, there is other factor that is specifically related to the oxidation of NADH.H+  produced in the cytosol; the kind of shuttle that is used for transporting the cytosolic NADH.H+  to the mitochondria, where this reduced cofactor will be oxidized in the Respiratory Chain.

2.- Which shuttle is used for transporting NADH.H+  produced in the cytosol to the mitochondria?

The internal mitochondria membrane is not permeable to NAD+ or NADH.H+  (the mitochondria has their own pool of these nucleotides).

There are two different mechanisms for transporting the reduction equivalents of cytosolic NADH.H+  through the internal membrane of the mitochondria:

a)      the malate aspartate shuttle.

b)      The glicerolphosphate shuttle.

a)    Malate-Aspartate Shuttle:

The reduction equivalents of the cytosolic NADH.H+  are transferred to oxalacetate to form malate, in a reaction catalyzed by a cytosolic malate dehydrogenase:

Cytosol: Oxalacetate + NADH.H+  —-à Malate + NAD+

Malate can pass through the mitochondria membranes and enter the matrix. Once in the matrix the malate is dehydrogenated by a mitochondrial malate dehydrogenase:

Mitochondria: Malate + NAD+ ——à oxalacetate + NADH.H+ 

The oxalacetate is transaminated to aspartate to go out of the mitochondria and once in the cytosol, the aspartate is transaminated to oxalacetate beginning a new cycle.

Since this 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 (2.5 or 3 ATP, depending on the equivalence followed)

b)   The glycerol phosphate shuttle

With this shuttle, the reduction equivalents of the cytosolic NADH.H+  are transferred to  dihydroxyacetone phosphate to form glycerol 3-phosphate,

                                     

The glycerol 3 (P) is dehydrogenated by a mitochondrial glycerol 3 (P) dehydrogenase  located on the outer surface of the inner membrane of the mitochondria, that transfer the reduction equivalents to FAD in the inner membrane:

Observe that the reduction equivalents have been transferred to FAD and not to NAD. It means that FADH2 is the cofactor that will be oxidized in the Respiratory Chain, and so, the use of this shuttle will yield less ATP: 1.5 or 2 ATP, depending on the equivalence that is followed

So, lets do  Permutation and Combination.

a)      2 ATP from SLP + 3 ATP if it is considered that the reduction equivalents of the cytoplasmatic NADH.H+  are transported  through the glycerol phosphate shuttle, and that for each FADH2 oxidized in the respiratory chain, the energy released can yield 1.5 ATP

b)      2 ATP from SLP + 4 ATP if it is considered  that the reduction equivalents of the cytoplasmatic NADH.H+  are transported through the glycerol phosphate shuttle, and that for each FADH2 oxidized in the respiratory chain, the energy released can yield 2 ATP

c)      2 ATP from SLP + 5 ATP if it is considered that the reduction equivalents of the cytoplasmatic NADH.H+  are transported through the malate aspartate shuttle and that for each NADH.H+ oxidized in the respiratory chain, the energy released can yield 2 .5 ATP

d)      2 ATP from SLP + 6 ATP if it is considered that the reduction equivalents of the cytoplasmatic NADH.H+  are transported  through the malate aspartate shuttle and that for each NADH.H+ oxidized in the respiratory chain, the energy released can yield 6 ATP 

In summary, the answer can be:

“ATP yield in Aerobic Glycolysis: 5, 6, 7 or 8 ATP/glucose!”.

If you are still unable to grab the concept , a excellent tutorial video can be found in link provided below.

References:

Lippincott Illustrated Reviews of Biochemistry

First Aid for the USMLE Step I

biochemistryquestions.wordpress.com
wikipedia.org/wiki/Glycolysis