What happens to NAD when it accepts a pair of high-energy electrons?

Most of the usable energy obtained from the breakdown of carbohydrates or fats is derived by oxidative phosphorylation, which takes place within mitochondria. For example, the breakdown of glucose by glycolysis and the citric acid cycle yields a full of four molecules of ATP, x molecules of NADH, and two molecules of FADH_ii (run into Chapter 2). Electrons from NADH and FADH₂ are then transferred to molecular oxygen, coupled to the formation of an additional 32 to 34 ATP molecules past oxidative phosphorylation. Electron transport and oxidative phosphorylation are critical activities of protein complexes in the inner mitochondrial membrane, which ultimately serve every bit the major source of cellular energy.

The Electron Ship Concatenation

During oxidative phosphorylation, electrons derived from NADH and FADH₂ combine with O₂, and the energy released from these oxidation/ reduction reactions is used to drive the synthesis of ATP from ADP. The transfer of electrons from NADH to O_ii is a very energy-yielding reaction, with ΔG°´ = -52.v kcal/mol for each pair of electrons transferred. To be harvested in usable grade, this energy must be produced gradually, past the passage of electrons through a series of carriers, which constitute the electron transport chain. These carriers are organized into 4 complexes in the inner mitochondrial membrane. A fifth poly peptide complex then serves to couple the energy-yielding reactions of electron transport to ATP synthesis.

Electrons from NADH enter the electron send chain in circuitous I, which consists of nearly 40 polypeptide chains (Effigy 10.eight). These electrons are initially transferred from NADH to flavin mononucleotide and then, through an iron-sulfur carrier, to coenzyme Q—an free energy-yielding process with ΔG°´ = -xvi.half-dozen kcal/mol. Coenzyme Q (also called ubiquinone) is a small, lipid-soluble molecule that carries electrons from complex I through the membrane to complex Iii, which consists of about ten polypeptides. In complex III, electrons are transferred from cytochrome b to cytochrome c—an energy-yielding reaction with ΔThou°´ = -10.i kcal/mol. Cytochrome c , a peripheral membrane protein spring to the outer face of the inner membrane, then carries electrons to circuitous IV (cytochrome oxidase), where they are finally transferred to O₂ (ΔG°´ = -25.8 kcal/mol).

A distinct protein complex (complex II), which consists of four polypeptides, receives electrons from the citric acid wheel intermediate, succinate (Effigy 10.9). These electrons are transferred to FADH₂, rather than to NADH, and so to coenzyme Q. From coenzyme Q, electrons are transferred to complex III and and so to complex 4 as already described. In contrast to the transfer of electrons from NADH to coenzyme Q at complex I, the transfer of electrons from FADH_ii to coenzyme Q is not associated with a significant decrease in gratis energy and, therefore, is not coupled to ATP synthesis. Consequently, the passage of electrons derived from FADH_ii through the electron transport chain yields energy only at complexes Three and IV.

Figure 10.nine

Transport of electrons from FADH_ii. Electrons from succinate enter the electron transport chain via FADH_ii in complex Ii. They are then transferred to coenzyme Q and carried through the rest of the electron ship chain as described in Effigy 10.8. The (more...)

The free free energy derived from the passage of electrons through complexes I, III, and IV is harvested past existence coupled to the synthesis of ATP. Importantly, the machinery past which the energy derived from these electron transport reactions is coupled to ATP synthesis is fundamentally different from the synthesis of ATP during glycolysis or the citric acrid bicycle. In the latter cases, a loftier-energy phosphate is transferred directly to ADP from the other substrate of an energy-yielding reaction. For example, in the final reaction of glycolysis, the loftier-energy phosphate of phosphoenolpyruvate is transferred to ADP, yielding pyruvate plus ATP (see Figure 2.32). Such direct transfer of high-free energy phosphate groups does non occur during electron transport. Instead, the energy derived from electron transport is coupled to the generation of a proton gradient across the inner mitochondrial membrane. The potential energy stored in this gradient is then harvested past a fifth protein complex, which couples the energetically favorable menstruation of protons dorsum across the membrane to the synthesis of ATP.

Chemiosmotic Coupling

The mechanism of coupling electron ship to ATP generation, chemiosmotic coupling, is a striking example of the relationship between structure and function in jail cell biology. The hypothesis of chemiosmotic coupling was outset proposed in 1961 by Peter Mitchell, who suggested that ATP is generated by the use of energy stored in the class of proton gradients beyond biological membranes, rather than by straight chemical transfer of high-energy groups. Biochemists were initially highly skeptical of this proposal, and the chemiosmotic hypothesis took more than a decade to win general credence in the scientific customs. Overwhelming testify somewhen accumulated in its favor, however, and chemiosmotic coupling is now recognized as a general mechanism of ATP generation, operating non only in mitochondria only also in chloroplasts and in bacteria, where ATP is generated via a proton gradient across the plasma membrane.

Electron ship through complexes I, III, and Iv is coupled to the ship of protons out of the interior of the mitochondrion (see Figure 10.8). Thus, the energy-yielding reactions of electron send are coupled to the transfer of protons from the matrix to the intermembrane space, which establishes a proton gradient beyond the inner membrane. Complexes I and IV appear to act equally proton pumps that transfer protons across the membrane as a issue of conformational changes induced by electron transport. In complex 3, protons are carried across the membrane by coenzyme Q, which accepts protons from the matrix at complexes I or II and releases them into the intermembrane space at complex III. Complexes I and 3 each transfer iv protons beyond the membrane per pair of electrons. In complex IV, two protons per pair of electrons are pumped across the membrane and another two protons per pair of electrons are combined with O₂ to form H₂O within the matrix. Thus, the equivalent of iv protons per pair of electrons are transported out of the mitochondrial matrix at each of these three complexes. This transfer of protons from the matrix to the intermembrane infinite plays the critical role of converting the energy derived from the oxidation/reduction reactions of electron transport to the potential free energy stored in a proton gradient.

Because protons are electrically charged particles, the potential energy stored in the proton gradient is electric likewise as chemical in nature. The electric component corresponds to the voltage difference beyond the inner mitochondrial membrane, with the matrix of the mitochondrion negative and the intermembrane space positive. The corresponding free energy is given by the equation

where F is the Faraday constant and ΔV is the membrane potential. The additional free energy respective to the difference in proton concentration across the membrane is given by the equation

where [H⁺]_i and [H⁺]_o refer, respectively, to the proton concentrations within and outside the mitochondria.

In metabolically active cells, protons are typically pumped out of the matrix such that the proton slope across the inner membrane corresponds to about one pH unit of measurement, or a tenfold lower concentration of protons inside mitochondria (Figure 10.ten). The pH of the mitochondrial matrix is therefore about 8, compared to the neutral pH (approximately 7) of the cytosol and intermembrane space. This gradient too generates an electrical potential of approximately 0.14 Five across the membrane, with the matrix negative. Both the pH gradient and the electric potential bulldoze protons back into the matrix from the cytosol, so they combine to class an electrochemical slope across the inner mitochondrial membrane, corresponding to a ΔG of approximately -5 kcal/mol per proton.

Figure 10.10

The electrochemical nature of the proton gradient. Since protons are positively charged, the proton gradient established across the inner mitochondrial membrane has both chemical and electric components. The chemical component is the proton concentration, (more...)

Because the phospholipid bilayer is impermeable to ions, protons are able to cross the membrane simply through a protein channel. This restriction allows the energy in the electrochemical gradient to be harnessed and converted to ATP every bit a issue of the activity of the fifth complex involved in oxidative phosphorylation, circuitous V, or ATP synthase (meet Figure 10.eight). ATP synthase is organized into two structurally distinct components, F₀ and F₁, which are linked past a slender stem (Effigy 10.11). The F₀ portion spans the inner membrane and provides a channel through which protons are able to flow back from the intermembrane space to the matrix. The energetically favorable return of protons to the matrix is coupled to ATP synthesis past the F₁ subunit, which catalyzes the synthesis of ATP from ADP and phosphate ions (P _i ). Detailed structural studies have established the mechanism of ATP synthase action, which involves mechanical coupling betwixt the F₀ and F₁ subunits. In particular, the menses of protons through F₀ drives the rotation of F₁, which acts equally a rotary motor to drive ATP synthesis.

Figure 10.eleven

Structure of ATP synthase. The mitochondrial ATP synthase (complex Five) consists of two multisubunit components, F₀ and F_ane, which are linked by a slender stem. F₀ spans the lipid bilayer, forming a channel through which protons can cross the membrane. (more than...)

It appears that the flow of four protons dorsum across the membrane through F₀ is required to drive the synthesis of one molecule of ATP by F₁, consistent with the proton transfers at complexes I, 3, and IV each contributing sufficient gratuitous energy to the proton gradient to bulldoze the synthesis of one ATP molecule. The oxidation of 1 molecule of NADH thus leads to the synthesis of iii molecules of ATP, whereas the oxidation of FADH_ii, which enters the electron transport chain at complex II, yields just two ATP molecules.

Send of Metabolites across the Inner Membrane

In addition to driving the synthesis of ATP, the potential energy stored in the electrochemical gradient drives the transport of modest molecules into and out of mitochondria. For example, the ATP synthesized within mitochondria has to be exported to the cytosol, while ADP and P _i need to be imported from the cytosol for ATP synthesis to continue. The electrochemical gradient generated past proton pumping provides energy required for the transport of these molecules and other metabolites that demand to be concentrated inside mitochondria (Figure 10.12).

Figure ten.12

Ship of metabolites across the mitochondrial inner membrane. The send of small molecules beyond the inner membrane is mediated by membrane-spanning transport proteins and driven past the electrochemical gradient. For example, ATP is exported from (more...)

The transport of ATP and ADP across the inner membrane is mediated by an integral membrane protein, the adenine nucleotide translocator, which transports one molecule of ADP into the mitochondrion in exchange for 1 molecule of ATP transferred from the mitochondrion to the cytosol. Because ATP carries more than negative accuse than ADP (-4 compared to -3), this substitution is driven by the voltage component of the electrochemical gradient. Since the proton gradient establishes a positive charge on the cytosolic side of the membrane, the export of ATP in exchange for ADP is energetically favorable.

The synthesis of ATP inside the mitochondrion requires phosphate ions (P _i ) as well as ADP, so P _i must also exist imported from the cytosol. This is mediated by another membrane transport protein, which imports phosphate (H₂PO₄ ^-) and exports hydroxyl ions (OH^-). This commutation is electrically neutral because both phosphate and hydroxyl ions have a charge of -1. However, the commutation is driven past the proton concentration gradient; the higher pH inside mitochondria corresponds to a higher concentration of hydroxyl ions, favoring their translocation to the cytosolic side of the membrane.

Energy from the electrochemical gradient is similarly used to drive the transport of other metabolites into mitochondria. For instance, the import of pyruvate from the cytosol (where it is produced by glycolysis) is mediated by a transporter that exchanges pyruvate for hydroxyl ions. Other intermediates of the citric acid cycle are able to shuttle between mitochondria and the cytosol by similar exchange mechanisms.

Box

Key Experiment: The Chemiosmotic Theory.

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Source: https://www.ncbi.nlm.nih.gov/books/NBK9885/

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