Fundamentals of Molecular Biology. Part 1: Molecular Cell Biology - A. N. Ogurtsov 2011

Generation of Proton-Motive Force and ATP Synthesis
Electron Transport Chain

The Free energy released during Glycolysis and The Citric Acid Cycle is primarily captured in the molecules of the reduced Coenzymes NADH and FADH₂. During cellular Respiration, electrons are released from NADH and FADH₂ and transferred to O₂, ultimately forming H₂O in the overall reactions

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The change in free energy in these highly exergonic reactions is ∆G = -52.6 kcal/mol for NADH and ∆G = -43.4 kcal/mol for FADH₂. Overall, The oxidation of one glucose molecule through glycolysis and The Citric Acid cycle yields 10 molecules of NADH and 2 molecules of FADH₂, meaning that the oxidation of these coenzymes yields

∆G = 10х(-52,6) + 2х(-43,4) = — 613 kcal/mol.

Thus, out of the total free energy that can be released during the Complete oxidation of glucose (-680 kcal/mol), over 90% is transferred to the coenzymes NADH and FADH₂ upon their reduction.

The amount of free energy released when one molecule of NADH or FADH₂ is oxidized by oxygen is sufficient to synthesize several molecules of ATP from ADP and P_i (this endergonic reaction requires only ∆G = +7.3 kcal/mol). Cell/35.html">Mitochondria maximize The Use of this energy by transferring electrons from NADH and FADH₂ along a chain of electron carriers (Figure 162), all of which—except for one—are integral Proteins of The inner mitochondrial membrane.

This stepwise transfer of electrons along the Respiratory Chain (electron transport chain) ensures the Controlled Release of energy in small increments and The conversion of these energy increments into a proton-motive force (Figure 154(2)).

The Main Components of the respiratory chain are four large multi-Structure/178.html">Protein Complexes:

Coenzyme Q (CoQ) and cytochrome c transfer electrons between these complexes. The energy released during electron relaxation within complexes I, III, and IV is sufficient to pump protons across the membrane via the proteins of these complexes (referred to as proton pumps), and this transmembrane transport establishes a proton concentration gradient across the inner mitochondrial membrane.

Figure 162 - Changes in redox potential and free energy during the sequential transfer of electrons along the respiratory chain

Because the outer mitochondrial membrane is permeable to protons while the inner membrane is not, this transmembrane proton transport causes the pH of the mitochondrial matrix to rise (and the proton concentration in the matrix to decrease) relative to the Cytosol and the intermembrane space. The matrix becomes negatively charged relative to the cytosol, establishing a Membrane Potential across the inner mitochondrial membrane.

As a result, the free energy released during the oxidation of NADH and FADH₂ is stored both as a proton concentration gradient and as an electrical potential across the inner mitochondrial membrane (collectively referred to as the proton-motive force).

The movement of protons back across the inner mitochondrial membrane driven by this proton-motive force is coupled with the synthesis of ATP from ADP and P_i by the enzyme ATP synthase (Figure 154(3)).

Complex I includes a flavin coenzyme (prosthetic group) flavin mononucleotide, FMN, in which, just as in FAD (Figure 163(a)), the active group is the flavin ring (isoalloxazine) (see Figure 155).

Figure 163 - Flavin Coenzymes: a - flavin adenine dinucleotide (FAD), b - flavin mononucleotide (FMN)

Flavin features a conjugated three-ring system that can accept two electrons and two protons upon reduction. In flavin mononucleotide (FMN), a phosphorylated polyol, ribitol, is attached to the flavin ring (Figure 163(b)).

Oxidative Phosphorylation is The process of synthesizing ATP from ADP and P_i driven by the energy released from electrons as they are transferred from NADH and FADH₂ to O₂. Oxidative phosphorylation serves as the primary source of ATP in aerobic non-photosynthetic Cells.