Most of the energy liberated during the oxidation of carbo hydrate, fatty acids, and amino acids is made available within mitochondria as reducing equivalents (—H or electrons) (Figure 1). The enzymes of the citric acid cycle and β-oxidation , the respiratory chain complexes, and the machinery for oxidative phosphorylation are all found in mitochondria. The respiratory chain collects and transports reducing equivalents, directing them to their final reaction with oxygen to form water, and oxidative phosphorylation is the process by which the liberated free energy is trapped as high-energy phosphate (ATP).

Fig1. Role of the respiratory chain of mitochondria in the conversion of food energy to ATP. Oxidation of the major foodstuffs leads to the generation of reducing equivalents (2H) that are collected by the respiratory chain for oxidation and coupled generation of ATP.

Components of the Respiratory Chain Are Contained in Four Large Protein Complexes Embedded in the Inner Mitochondrial Membrane

 Electrons flow through the respiratory chain through a redox span of 1.1 V from NAD⁺/NADH to O₂ /2H₂O , passing through three large protein complexes: NADH-Q oxidoreductase (Complex I), where electrons are transferred from NADH to coenzyme Q (Q) (also called ubiquinone); Q-cytochrome c oxidoreductase (Complex III), which passes the electrons on to cytochrome c; and cytochrome c oxidase (Complex IV), which completes the chain, passing the electrons to O₂ and causing it to be reduced to H₂O (Figure 2). Some substrates with more positive redox potentials than NAD+/NADH (eg, succinate) pass electrons to Q via a fourth complex, succinate-Q reductase (Complex II), rather than Complex I. The four complexes are embedded in the inner mitochondrial membrane, but Q and cytochrome c are mobile. Q diffuses rapidly within the membrane, while cytochrome c is a soluble protein.

Fig2. Overview of electron flow through the respiratory chain. (cyt, cytochrome; Q, coenzyme Q or ubiquinone.)

Flavoproteins & Iron-Sulfur Proteins (Fe-S) Are Components of the Respiratory Chain Complexes

Flavoproteins are important components of Complexes I and II. The oxidized flavin nucleotide (flavin mononucleotide [FMN] or flavin adenine dinucleotide [FAD]) can be reduced in reactions involving the transfer of two electrons (to form FMNH₂ or FADH₂ ), but they can also accept one electron to form the semiquinone . Iron sulfur proteins (nonheme iron proteins, Fe-S) are found in Complexes I, II, and III. These may contain one, two, or four Fe atoms linked to inorganic sulfur atoms and/or via cysteine SH groups to the protein (Figure 3). The Fe-S take part in single electron transfer reactions in which one Fe atom under goes oxidoreduction between Fe²⁺ and Fe³⁺.

FIG3. Iron-sulfur proteins (Fe-S). (A) The simplest Fe-S with one Fe bound by four cysteines. (B) 2Fe-2S center. (C) 4Fe-4S center. (Cys, cysteine; Pr, apoprotein; Ⓢ, inorganic sulfur.)

Q Accepts Electrons via Complexes I & II

NADH-Q oxidoreductase or Complex I is a large L-shaped multisubunit protein that catalyzes electron transfer from NADH to Q, and during the process four H⁺ are transferred across the membrane into the intermembrane space:

NADH + Q + 5H⁺ matrix → NAD + QH₂ + 4H⁺ _{intermembrance space}

Electrons are transferred from NADH to FMN initially, then to a series of Fe-S centers, and finally to Q (Figure 4). In Complex II (succinate-Q reductase), FADH₂ is formed during the conversion of succinate to fumarate in the citric acid cycle  and electrons are then passed via several Fe-S centers to Q (see Figure 4). Glycerol-3-phosphate (generated in the breakdown of triacylglycerols or from glycolysis) and acyl-CoA also pass electrons to Q via different pathways involving flavoproteins (see Figure 4).

Fig4. Flow of electrons through the respiratory chain complexes, showing the entry points for reducing equivalents from important substrates. Q and cyt c are mobile components of the system as indicated by the dotted arrows. The flow through Complex III (the Q cycle) is shown in more detail in Figure 13–6. (cyt, cytochrome; ETF, electron transferring flavoprotein; Fe-S, iron-sulfur protein; Q, coenzyme Q or ubiquinone.)

The Q Cycle Couples Electron Transfer to Proton Transport in Complex III

Electrons are passed from QH2 to cytochrome c via Complex III (Q-cytochrome c oxidoreductase):

The process is believed to involve cytochromes c₁ , b_L , and b_H and a Rieske Fe-S (an unusual Fe-S in which one of the Fe atoms is linked to two histidine residues rather than two cysteine residues) (see Figure 3) and is known as the Q cycle (Figure 5). Q may exist in three forms: the oxidized quinone, the reduced quinol, or the semiquinone (see Figure 5). The semiquinone is formed transiently during the cycle, one turn of which results in the oxidation of 2QH₂ to Q, releasing 4H⁺ into the intermembrane space, and the reduction of one Q to QH₂ , causing 2H⁺ to be taken up from the matrix (see Figure 5). Note that while Q carries two electrons, the cytochromes carry only one, thus the oxidation of one QH₂ is coupled to the reduction of two molecules of cytochrome c via the Q cycle.

Fig5. The Q cycle.During the oxidation of QH2 to Q, one electron is donated to cyt c via a Rieske Fe-S and cyt c1 and the second to a Q to form the semiquinone via cyt b_L and cyt b_H , with 2H⁺ being released into the intermembrane space. A similar process then occurs with a second QH₂ , but in this case the second electron is donated to the semiquinone, reducing it to QH₂ , and 2H⁺ are taken up from the matrix. (cyt, cytochrome; Fe-S, iron-sulfur protein; Q, coenzyme Q or ubiquinone.)

Molecular Oxygen Is Reduced to Water via Complex IV

Reduced cytochromecis oxidized by Complex IV (cytochromec oxidase), with the concomitant reduction of O₂ to two molecules of water:

Four electrons are transferred from cytochrome c to O₂ via two heme groups, a and a₃ , and Cu(see Figure 4). Electrons are passed initially to a Cu center (Cu_A ), which contains 2Cu atoms linked to two protein cysteine-SH groups (resembling an Fe-S), then in sequence to heme a, heme a₃ , a second Cu center, Cu_B , which is linked to heme a₃ , and finally to O₂ . Eight H⁺ are removed from the matrix, of which four are used to form two water molecules and four are pumped into the intermembrane space. Thus, for every pair of electrons passing down the chain from NADH or FADH₂ , 2H⁺ are pumped across the membrane by Complex IV. The O2 remains tightly bound to Complex IV until it is fully reduced, and this minimizes the release of potentially damaging intermediates such as super oxide anions or peroxide which are formed when O₂ accepts one or two electrons, respectively .

مواضيع ذات صلة

The Respiratory Chain Provides Most Of The Energy Captured During Catabolism

Electron Transport Via The Respiratory Chain Creates A Proton Gradient Which Drives The Synthesis of ATP

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