The flow of electrons through the respiratory chain generates ATP by the process of oxidative phosphorylation. The chemiosmotic theory, proposed by Peter Mitchell in 1961, postulates that the two processes are coupled by a proton gradient across the inner mitochondrial membrane so that the proton motive force caused by the electrochemical potential difference (negative on the matrix side) drives the mechanism of ATP synthesis. As we have seen, Complexes I, III, and IV act as proton pumps, moving H+ from the mitochondrial matrix to the intermembrane space. Since the inner mitochondrial membrane is impermeable to ions in general and particularly to protons, these accumulate in the intermembrane space, creating the proton motive force predicted by the chemiosmotic theory.

A Membrane-Located ATP Synthase Functions as a Rotary Motor to Form ATP

The proton motive force drives a membrane-located ATP synthase that forms ATP in the presence of P_i + ADP. ATP synthase is embedded in the inner membrane, together with the respiratory chain complexes (Figure 1). Several subunits of the protein form a ball-like shape arranged around an axis known as F₁ , which projects into the matrix and contains the phosphorylation mechanism (Figure 2). F₁ is attached to a membrane protein complex known as F₀ , which also consists of several protein subunits. F₀ spans the membrane and forms a proton channel. As protons flow through F0 driven by the proton gradient across the membrane it rotates, driving the production of ATP in the F₁ complex (see Figures 1 and 2). This is thought to occur by a binding change mechanism in which the conformation of the β subunits in F1 is changed as the axis rotates from one that binds ATP tightly to one that releases ATP and binds ADP and Pi so that the next ATP can be formed. As indicated earlier, for each NADH oxidized, Complexes I and III translocate four protons each and Complex IV translocates two.

Fig1. The chemiosmotic theory of oxidative phosphorylation. Complexes I, III, and IV act as proton pumps creating a proton gradient across the membrane, which is negative on the matrix side. The proton motive force generated drives the synthesis of ATP as the pro tons flow back into the matrix through the ATP synthase enzyme (Figure 2). Uncouplers increase the permeability of the membrane to ions, collapsing the proton gradient by allowing the H⁺ to pass across without going through the ATP synthase, and thus uncouple electron flow through the respiratory complexes from ATP synthesis. (cyt, cytochrome; Q, coenzyme Q or ubiquinone.)

Fig2. Mechanism of ATP production by ATP synthase. The enzyme complex consists of an F₀ subcomplex which is a disk of “C” protein subunits. Attached is a γ subunit in the form of a “bent axle.” Protons passing through the disk of “C” units cause it and the attached γ subunit to rotate. The γ subunit fits inside the F1 subcomplex of three α and three β subunits, which are fixed to the mem brane and do not rotate. ADP and Pi are taken up sequentially by the β subunits to form ATP, which is expelled as the rotating γ subunit squeezes each β subunit in turn and changes its conformation. Thus, three ATP molecules are generated per revolution. For clarity, not all the subunits that have been identified are shown—eg, the “axle” also contains an ε subunit.

مواضيع ذات صلة

The Respiratory Chain Provides Most Of The Energy Captured During Catabolism

The Respiratory Chain Oxidizes Reducing Equivalents & Acts as A Proton Pump

دورة الخلية وتخليق الدنا Cell Cycle & DNA Synthesis

Oxygenases Catalyze The Direct Transfer & Incorporation of Oxygen Into A Substrate Molecule

Hydroperoxidases Use Hydrogen Peroxide or an Organic Peroxide as Substrate

اضطرابات استقلاب النوكليوتيدات البيريميدينية

اضطرابات استقلاب النكليوتيدات البورينية

تخليق النوكليوتيدات منقوصة الاكسجين ( dNTPs )

تقويض النوكليوتيدات البيريميدينية

Dehydrogenases Perform Two Main Functions

Oxidases Use Oxygen As A Hydrogen Acceptor

تخليق النكليوتيدات البيريميدينية