Respiratory assemblies membranes

Fat depots provide fatty acids for cellular fuel. The oxidation of fatty acids produces NADH and FADH2, which are oxidized by oxygen (via the respiratory assemblies in the inner membrane of mitochondria, Chap. 14) with the concomitant production of water. 

The electron carriers in the respiratory assembly of the inner mitochondrial membrane are quinones, flavins, iron-sulfur complexes, heme groups of cytochromes, and copper ions. Electrons from NADH are transferred to the FMN prosthetic group of NADH-Q oxidoreductase (Complex I), the first of four complexes. This oxidoreductase also contains Fe-S centers. The electrons emerge in QH2, the reduced form of ubiquinone (Q). The citric acid cycle enzyme succinate dehydrogenase is a component of the succinate-Q reductase complex (Complex II), which donates electrons from FADH2 to Q to form QH2.This highly mobile hydrophobic carrier transfers its electrons to Q-cytochrome c oxidoreductase (Complex III), a complex that contains cytochromes h and c j and an Fe-S center. This complex reduces cytochrome c, a water-soluble peripheral membrane protein. Cytochrome c, like Q, is a mobile carrier of electrons, which it then transfers to cytochrome c oxidase (Complex IV). This complex contains cytochromes a and a 3 and three copper ions. A heme iron ion and a copper ion in this oxidase transfer electrons to O2, the ultimate acceptor, to form H2O. 

Aerobic respiration, the process that generates most of the energy required in eukaryotes, takes place in mitochondria. Embedded in the inner membrane of the mitochondrion are respiratory assemblies, where ATP is synthesized. 

Each mitochondrion (plural mitochondria) is bounded by two membranes (Figure 2.24a). The smooth outer membrane is relatively porous, because it is permeable to most molecules with masses less than 10,000 D. The inner membrane, which is impermeable to ions and a variety of organic molecules, projects inward into folds that are called cristae (singular crista). Embedded in this membrane are structures composed of molecular complexes and called respiratory assemblies (described in Chapter 10) that are responsible for the synthesis of ATP. Also present are a series of proteins that are responsible for the transport of specific molecules and ions. 

Describe the compartments and membranes of mitochondria and locate the respiratory assemblies and the N and P sides of the inner membrane. 

Mitochondria are surrounded by two lipoprotein membranes, together about 180 A thick. The inner membrane is folded into the cell as a series of invaginations known as cristae. About one-quarter of the protein part of the cristae consists of oxysomes (respiratory assemblies), i.e. ordered arrangements of riboflavine-protein, coenzyme Q, cytochromes b, c, c, a, and a (in that sequence) together with their specific proteins. Ferredoxins (Section 11.0) also play an important part. The tricarboxylic acid cycle ensures the reduction of the first two members of the above chain, and each member is oxidized by the member on its right (in the above list), and so on to the end of the chain at cytochrome a which is in equilibrium with atmospheric oxygen. 

The respiratory chain and other enzymes involved in oxidative phosphorylation comprise an organized group, or respiratory assembly, associated with the inner mitochondrial membrane (Lehninger, 1951). These respiratory assemblies seem to be distributed uniformly over or within the surface of the inner membrane, with center-to-center distance between assemblies of the order of 20 nm. Thus, there is one complete respiratory assembly for each 400 to 500 nm of inner membrane surface (Klingenberg, 1967 Lehninger, 1970). The metabolic activity of mitochondria is, therefore, proportional to the amount of inner mitochondrial membranes and to the number of respiratory assemblies they contain (Dempsey, 1956 Palade, 1956 Munn, 1969). Obviously, there is a reciprocal relationship between the amount of membrane and matrix in mitochondria with large numbers of cristae, the matrix compartment is materially reduced. Table I summarizes some typical figures. 

Defects of nuclear DNA also cause mitochondrial diseases. As mentioned above, the vast majority of mitochondrial proteins are encoded by nDNA, synthesized in the cytoplasm and imported into the mitochondria through a complex series of steps. Diseases can be due to mutations in genes encoding respiratory chain subunits, ancillary proteins controlling the proper assembly of the respiratory chain complexes, proteins controlling the importation machinery, or proteins controlling the lipid composition of the inner membrane. All these disorders will be transmitted by mendelian inheritance. From a biochemical point of view, all areas of mitochondrial metabolism can be affected (see below). 

Schmidt, M.C., et al. 1998. Translocation of human calcitonin in respiratory nasal epithelium is associated with self-assembly in lipid membrane. Biochemistry 37 16582. 

Coxl7, an 8.1-kDa cysteine-rich protein, was the first copper chaperone to be identified. Saccharomyces cerevisiae harboring mutations in coxl 7 are respiratory deficient, a phenotype resulting from their inability to assemble a functional cytochrome c oxidase complex (Glerum et al., 1996a). coxl7 mutant yeast are, however, able to express all the subunits of the cytochrome c oxidase complex, indicating that the lesion must lie in a posttranslational step that is essential for assembly of the functional complex in the mitochondrial membrane. Unlike other cytochrome c... 

Sargent, F., Berks, B.C., Palmer, T. (2002). Assembly of membrane-bound respiratory complexes by the Tat protein-transport system. Arch. Microbiol. 178 77-84. 

Embedded within the inner membrane are the protein electron carriers (primarily) cytochromes, which constitute the respiratory chain. They are assembled in the form of five multiprotein complexes, named I, II, III, IV, and V. Smaller carriers, such as coenzyme Q and cytochrome c, also participate in carrying electrons. Figure 15.2b shows metabolic reactions occuring inside the mitochondrial matrix and movement of electrons through the complexes in the inner mitochondrial membrane. Note that electrons are ultimately donated with protons to oxygen to form water and that Complex V does not function in transport of electrons. 

The respiratory burst results from the activity of NADPH oxidase, which catalyzes the transfer of an electron from NADPH to O2 to form superoxide (Fig. 24.12). NADPH oxidase is assembled from cytosol and membranous proteins recruited into the phagolysosome membrane as it surrounds an invading microorganism. 

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