Why can mitochondria make only 34 molecules (not 61 molecules) of ATP from the energy obtained from the oxidation in the electron transfer system of NADH and FADH2 generated by oxidation of glucose in glycolysis and the tricarboxylic acid cycle?

The electron transfer system oxidizes 10 mol of NADH and 2 mol of FADH2 obtained from glycolyses and the tricarboxylic acid cycle, and up to 34 mol of ATP can be obtained by the electron transfer system alone. Complexes I and II take energy from NADH and FADH2, and complexes I, III, and IV are also proton pumps that pump hydrogen ions against a concentration gradient. The reactions carried out by the four enzymes, known as complexes I–IV, and their Gibbs free energies are as follows;

  • Complex I: (NADH + H+ + CoQ → NAD+ + CoQH2 — ΔG˚′(1) = -71 kJ/mol)×10
  • Complex Ⅱ: (FADH2 + succinic acid + CoQ → FAD + CoQH2 + Fumaric acid — ΔG˚′(2) =-2.9 kJ/mol)×2
  • Complex Ⅲ:(CoQH2 + 2 cyt c(Fe3+) → CoQ + 2 cyt c(Fe2+) + 2H+ — ΔG˚′(3) = -41 kJ/moll)×12
  • Complex Ⅳ:(4 cyt c(Fe2+) + O2 + 4H+ → 4 cyt c(Fe3+) + 2H2O — ΔG˚′(4) = -110 kJ/mol)×6

Therefore, the ‘net’ reaction, from complex I–IV, is as follows:
10 NADH + 2 FADH2 + 6 O2+ 2 Succinic acid → 12 H2O + 10 NAD + 2 FAD + 2 Fumaric acid — ΔG˚′ (total)


ΔGo' (total)= 10ΔGo'(1) + 2Go'(2) + 12ΔGo'(3) + 6ΔGo'(4)
= 10*(-71) + 2*(-2.9) + 12*(-41) + 6*(-110) kJ/mol
= -1867.8 kJ/mol

The following reactions then occurs in complex V using the above ΔG˚′ (total);
ADP + Pi → ATP , ΔGo'(5)= -30.5 kJ/mol

Simply considering abovementioned only, the amount of ATP that can be generated from the energy derived from a single molecule of glucose entering the electron transfer system via NADH or FADH2 is as follows; -1867.8/-30.5 =61.2 ATPs

So, my question is as folilows;

Why can mitochondria make only 34 molecules (not 61 molecules) of ATP from the energy obtained from a single molecule of glucose in the electron transfer system?

I would like to ask this question especially from the perspective of Gibbs energy balance (in terms of energy loss).



1 Answer 1


The fundamental flaw in the poster’s logic is the implicit supposition that if a mitochondrial (or other) oxidation reaction has a standard Gibbs Free Energy change of -x kJ/mol, all of that can be used to drive the reaction ADP + Pi → ATP; and that one can just divide x by 30.5 to find how much ATP is produced.

One cannot.

One needs to consider the actual physico-chemical reactions of the oxidations and the subsequent phosphorylations of ADP. When you do this you will find that much of the free energy of the oxidation reactions is not used to drive a chemical reaction, but is converted into (‘lost’, in the terms of the poster) heat energy.

Even if one considers the simplest situation, ‘substrate level’ phosphorylations — reactions in which the oxidation of NAD+ is coupled directly to the synthesis of ATP or GTP — there is no logical reason why the free energy change should be zero. The oxidation reaction may well have a –ΔG˚′ of greater absolute magnitude than the +ΔG˚′ required to synthesize NTP, and the difference will be released as heat. This is indeed the case for the succinyl-CoA synthetase reaction which generates GTP in the tricarboxylic acid cycle.

However the mitochondrial oxidation reactions are not coupled directly to generation of ATP. They are used to pump protons across a membrane, and to generate a membrane potential, which is the basis of the proton-motive force used to drive ATP synthetase and synthesize ATP. There is no reason to expect that all the free energy from the oxidation reactions will be conserved as a proton gradient and membrane potential, and good reason to suppose that it will not.


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