Mitochondria electron transfer

Under aerobic conditions, the hydrogen atoms of NtUDH are oxidised within the mitochondrion pyruvate is also oxidised in the mitochondrion (Figure 9.15). However, NADH cannot be transported across the inner mitochondrial membrane, and neither can the hydrogen atoms themselves. This problem is overcome by means of a substrate shuttle. In principle, this involves a reaction between NADH and an oxidised substrate to produce a reduced product in the cytosol, followed by transport of the reduced product into the mitochondrion, where it is oxidised to produce hydrogen atoms or electrons, for entry into the electron transfer chain. Finally, the oxidised compound is transported back into the cytosol. The principle of the shuttle is shown in Figure 9.16. 

It has been known for many years that the mitochondrion shows a respiration-linked transport of a number of ions. Of these, calcium has attracted the most attention since it depends on a specific transport system with high-affinity binding sites. The uptake of calcium usually also involves a permeant anion, but in the absence of this, protons are ejected as the electron transfer system operates. The result is either the accumulation of calcium salts in the mitochondrial matrix or an alkalinization of the interior of the mitochondrion. The transfer of calcium inwards stimulates oxygen utilization but provides an alternative to the oxidative phosphorylation of ADP618 ... 

Eugene Kennedy and Albert Lehninger showed in 1948 that, in eulcaiyotes, the entire set of reactions of the citric acid cycle takes place in mitochondria. Isolated mitochondria were found to contain not only all the enzymes and coenzymes required for the citric acid cycle, but also all the enzymes and proteins necessaiy for the last stage of respiration—electron transfer and ATP synthesis by oxidative phosphoiylation. As we shall see in later chapters, mitochondria also contain the enzymes for the oxidation of fatty acids and some amino acids to acetyl-CoA, and the oxidative degradation of other amino acids to a-ketoglutarate, succinyl-CoA, or oxaloacetate. Thus, in nonphotosynthetic eulcaiyotes, the mitochondrion is the site of most energy-yielding... 

FIGURE 19-1 Biochemical anatomy of a mitochondrion. The convolutions (cristae) of the inner membrane provide a very large surface area. The inner membrane of a single liver mitochondrion may have more than 10,000 sets of electron-transfer systems (respiratory chains) and ATP synthase molecules, distributed over the membrane surface. Heart mitochondria, which have more profuse cristae and thus a much larger area of inner membrane, contain more than three times as many sets of electron-transfer systems as liver mitochondria. The mitochondrial pool of coenzymes and intermediates is functionally separate from the cytosolic pool. The mitochondria of invertebrates, plants, and microbial eukaryotes are similar to those shown here, but with much variation in size, shape, and degree of convolution of the inner membrane. 

How Many Protons in a Mitochondrion Electron transfer translocates protons from the mitochondrial matrix to the external medium, establishing a pH gradient across the inner membrane (outside more acidic than inside). The tendency of protons to diffuse back into the matrix is the driving force for ATP synthesis by ATP synthase. During oxidative phosphorylation by a suspension of mitochondria in a medium of pH 7.4, the pH of the matrix has been measured as 7.7. 

Mitchell based his concept on the suggestion that as electron is transported along the respiratory chain, H+ ions are ejected to cytoplasm (the mitochondrion environment). As a consequence, a gradient of H+ ion concentration occurs in external and internal mitochondrial spaces. Of course, this H+ ion concentration gradient is supported by electron transfer free energy decrease and in the case of membrane impermeability for H+ ions. 

Degree of Reduction of Electron Carriers in the Respiratory Chain The degree of reduction of each carrier in the respiratory chain is determined by conditions in the mitochondrion. For example, when NADH and 02 are abundant, the steady-state degree of reduction of the carriers decreases as electrons pass from the substrate to 02. When electron transfer is blocked, the carriers before the block become more reduced and those beyond the block become more oxidized (see Fig. 19-6). For each of the conditions below, predict the state of oxidation of ubiquinone and cytochromes b, clt c, and a + a3. 

Menadione (vitamin K3),phylloquinone (vitamin Kj), and ascorbate (vitamin C) have been used to donate electrons to cytochrome c. For example, ascorbate is oxidized to dehydroascorbate as it uses its electrons to reduce cytochrome c directly. The dehydroascorbate is quickly reduced to ascorbate in the mitochondrion by NADH or FADH2. Menadione appears to improve cellular phosphate metabolism and to enhance electron transfer after a respiratory Complex I block. 

THE RATIO OF PROTONS EXTRUDED FROM THE MITOCHONDRION TO ELECTRONS TRANSFERRED TO OXYGEN... 

Repeating units of varying composition can apparently be sufficiently complimentary to form a given membrane, and enzymatic properties are often parcelled out in blocs to different species of repeating units. For example, it is felt that the inner membrane of the mitochondrion may be comprised of as many as ten species of elementary particles, each chemically and enzymatically different, with electron transfer involving a set of four of these. 

Fig. 3 Mitochondrion-dependent signaling at a early apoptotic stage. The three mayor actions of NO in mitochondria are indicated as reversible binding to complex IV, inhibition of electron transfer at complex III, and oxidation of ubiquinol yielding Oy. The fates of Oy, H2O2, and NO are indicated together with their release into cytosol (the former through VDAC). Modulation of JNK activity (stimulation by H2O2 and inhibition by NO) is indicated. JNK phosphorylates Bcl-2 and Bcl-XL...

Aerobic glycolysis Metabolism of glucose to pyruvate. Pyruvate in the presence of sufficient oxygen can be metabolized to CO via the tricarboxylic acid cycle in the mitochondrion-producing NADH and FADH, which contribute elections through the electron transfer chain to molecular oxygen producing H O and ATP. 

These enzymes contain FAD, and the reduced coenzyme FADH2 that is formed is reoxidized by an electron transferring flavoprotein (Chapter 15), which also contains FAD. This protein carries the electrons abstracted in the oxidation process to the inner membrane of the mitochondrion where they enter the mitochondrial electron transport system, as depicted in Fig. 10-5 and as discussed in detail in... 

In the electron transport chain, CcO receives electrons from cytochrome c, a water-soluble heme protein, on the cytoplasmic side of the membrane, and transfers them through a series of electron transfer steps to the active site, which contains a heme iron and a copper, where the electrons are used to reduce the molecular oxygen. The protons needed for this reaction are taken from the mitochondrion matrix side throngh two proton-conducting channels. In addition to these chemical protons, four more protons, per every oxygen molecule reduced, are translocated across the membrane. The overall enzymatic reaction of CcO is... 

Fig. 13.1.1. Schematic overview of mitochondrial oxidative phosphorylation. A part of the mitochondrion is represented, showing the outer mitochondrial membrane (OMM), inner mitochondrial membrane (IMM) and crista (an invagination of the inner membrane). Substrates for oxidation enter the mitochondrion through specific carrier proteins, e.g., the pyruvate transporter, (PyrT). Reducing equivalents from fatty acyl CoA dehydrogenases, pyruvate dehydrogenase and the TCA cycle are delivered to the electron transport chain through NADH, succinate ubiquinol oxidoreductase (SQO), electron transfer flavoprotein (ETF) and its ubiquinol-...

In many microorganisms and in the mitochondrion of eukaryotic cells, the driving force is provided by electron transfers generated by the oxidation of a substrate in a process called respiration. For example, the mitochondrial respiratory system is made of four membrane-bound complexes... 

We saw in Case studies 4.2 and 4.3 that exergonic electron transfer processes drive the synthesis of ATP in the mitochondrion during oxidative phosphorylation. Electron transfer between protein-bound co-factors or between proteins also plays a role in other biological processes, such as photosynthesis (Section 5.11 and Case study 12.3), nitrogen fixation, the reduction of atmospheric Nj to NH3 by certain microorganisms, and the mechcuiisms of action of oxidoreductcises, which are enzymes that catalyze redox reactions. 

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