Textbook - BIOLOGICAL CHEMISTRY - Gubsky Yu.I. - 2000

Chapter II. GENERAL PATTERNS OF METABOLISM

CHAPTER 9. BIOENERGETIC PROCESSES: ELECTRON TRANSPORT; OXIDATIVE PHOSPHORYLATION IN MITOCHONDRIA

9.3. MOLECULAR ORGANIZATION OF THE BIOLOGICAL OXIDATION CHAIN IN MITOCHONDRIA

The Biological Oxidation system localized in the mitochondrial membranes performs the dehydrogenation of organic substrates and the sequential transfer of reducing equivalents to oxygen via a series of intermediate carriers—electron and proton transporters. This system is organized into the Electron Transport Chain, or the mitochondrial Respiratory Chain.

The mitochondrial respiratory chain is a set of molecular components (Enzymes and Coenzymes) embedded in the lipid matrix of The inner mitochondrial membranes that carry out The oxidation of biological substrates and the sequential, stepwise transport of reducing equivalents to oxygen with The formation of a Water molecule.

Components of the mitochondrial respiratory chain:

NADH dehydrogenase is a component of the respiratory chain that oxidizes reduced NAD⁺ (NADH); it is part of the molecular complex of the inner mitochondrial membranes known as NADH-coenzyme Q reductase.

Succinate dehydrogenase is a component of the respiratory chain that oxidizes succinic acid; it is part of the molecular complex called succinate-coenzyme Q reductase.

Coenzyme Q (ubiquinone) is a lipid-soluble quinone with an isoprenoid side chain containing ten five-carbon isoprenoid residues in mammalian Tissues (Q₁₀). Ubiquinone Functions as a collector of reducing equivalents, accepting protons and electrons not only from FMN-dependent NADH dehydrogenase, but also from FAD-dependent mitochondrial dehydrogenases (such as succinate dehydrogenase and the fatty acid β-oxidation system dehydrogenases).

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Mitochondrial Cytochromes:

Cytochrome b.

Cytochrome c₁.

Cytochrome c.

Cytochrome a.

Cytochrome a₃.

Iron-sulfur Proteins containing non-heme iron (FeS) are proteins associated with mitochondrial Flavoproteins (metalloflavoproteins) and cytochrome b.

The sequence of Electron transfer from one component of the mitochondrial respiratory chain to another is determined by the standard oxidation-reduction potentials of these components—Table 9.1.

Table 9.1. Standard oxidation-reduction potentials of the components of the mitochondrial respiratory chain

Individual enzymes and coenzymes that make up the respiratory chain are structurally integrated into supramolecular (multi-enzyme) complexes embedded in the lipid matrix of the inner mitochondrial membranes, which creates the steric conditions necessary for the efficient course of oxidation-reduction reactions.

Complexes of the respiratory chain of the inner mitochondrial membranes

NADH-coenzyme Q reductase is an enzyme complex (a flavoprotein containing FMN) that oxidizes NADH and transfers reducing equivalents to coenzyme Q (ubiquinone); within NADH-coenzyme Q reductase, NADH dehydrogenase is associated with FeS proteins (referred to as complex I).

Succinate-coenzyme Q reductase is an enzyme complex (an FAD-dependent flavoprotein) that oxidizes succinate, reducing coenzyme Q; the complex includes the flavoprotein succinate dehydrogenase associated with an FeS protein (complex II).

Coenzyme Q-cytochrome c-reductase (ubiquinol dehydrogenase) is an enzyme complex consisting of cytochrome b, an FeS protein, and cytochrome c₁; this enzyme complex transports electrons from reduced coenzyme Q (QH₂) to cytochrome c (complex III).

Cytochrome c oxidase is an enzyme complex consisting of cytochromes a and a₃ (complex IV); this complex performs The final stage of biological oxidation—the electron-mediated reduction of molecular oxygen; like other oxidases, it contains copper ions.

Pathways for the incorporation of reducing equivalents into the mitochondrial respiratory chain

1. Incorporation of protons and electrons into the respiratory chain via the FMN of the flavoprotein NADH-coenzyme Q reductase. Through this pathway, reducing equivalents cleaved from corresponding substrates by NADH-dependent dehydrogenases are delivered to the ubiquinone molecule.

2. Incorporation of protons and electrons into the respiratory chain via the FAD of succinate-coenzyme Q reductase and certain other FAD-dependent dehydrogenases. Through this pathway, reducing equivalents from succinic acid—a metabolite of The Tricarboxylic Acid Cycle—and certain other substrates are supplied to ubiquinone.

The sequence of incorporation of individual components of the electron and proton transport system into the mitochondrial respiratory chain is shown in Figure 9.2.

As can be seen from the diagram, the mitochondrial respiratory chain is organized in such a way that The transfer of reducing equivalents (electrons) within it proceeds from the electronegative end (flavoproteins) to the electropositive cytochrome a₃. Most metabolites (substrates of Glycolysis, the tricarboxylic acid cycle, etc.) transfer hydrogen atoms to the respiratory chain via NADH dehydrogenase (E-FMN); succinate and CoA derivatives of Fatty acids donate electrons and protons to coenzyme Q via specific flavoproteins (E-FAD), bypassing the FMN-dependent flavoprotein.

Ubiquinone is the final component of the mitochondrial respiratory chain capable of transporting both electrons and protons. At the level of cytochrome b, the pathways of electrons and protons diverge—protons cross from the inner surface of the mitochondrial membrane to the outer surface, while electrons are transported via a series of cytochromes to cytochrome a₃, which reduces oxygen:

The interaction of reduced oxygen with free protons of the mitochondrial matrix leads to the formation of a water molecule:

Fig. 9.2. Schematic Organization OF THE mitochondrial respiratory chain. I–IV represent The electron transport complexes of the mitochondrial membranes. Abbreviations: α-KG — α-ketoglutarate; β-HO-acyl-CoA — β-hydroxyacyl-CoA; Gl-3-P — glycerol-3-phosphate.