Mitochondria electron transfer reactions

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. 

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... 

Electrons in the iron-sulfur clusters of NADH-Q oxidoreduetase are shuttled to coenzyme Q. The flow of two electrons from NADH to coenzyme Q through NADH-Q oxidoreduetase leads to the pumping offour hydrogen ions out of the matrix of the mitochondrion. The details of this process remain the subject of active investigation. However, the coupled electron- proton transfer reactions of Q are crucial. NADH binds to a site on the vertical arm and transfers its electrons to FMN. These electrons flow within the vertical unit to three 4Fe-4S centers and then to a bound Q. The reduction of Q to... 

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... 

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. 

Ascorbic acid is now well established as an essential factor in many hydroxylation reactions of the type RH + O ROH. On the face of it this seems a paradoxical role for a reducing substance but not if one treats the vitamin as a redox couple, e.g. ascorbic acid/dehydroascorbic acid (H2A/A) which will undergo cycling, like the cytochromes. After all, what is really meant by reference to, say, cytochrome c in the context of its role in the mitochondrion is cytochrome c (Fe )/ cytochrome c (Fe ) because, in helping to transfer electrons from metabolites towards oxygen, the cytochrome molecule continually... 

A more complex and more efficient shutde mechanism is the malate-aspartate shuttle, which has been found in mammalian kidney, liver, and heart. This shuttle uses the fact that malate can cross the mitochondrial membrane, while oxaloacetate cannot. The noteworthy point about this shuttle mechanism is that the transfer of electrons from NADH in the cytosol produces NADH in the mitochondrion. In the cytosol, oxaloacetate is reduced to malate by the cytosolic malate dehydrogenase, accompanied by the oxidation of cytosolic NADH to NAD+ (Figure 20.24). The malate then crosses the mitochondrial membrane. In the mitochondrion, the conversion of malate back to oxaloacetate is catalyzed by the mitochondrial malate dehydrogenase (one of the enzymes of the citric acid cycle). Oxaloacetate is converted to aspartate, which can also cross the mitochondrial membrane. Aspartate is converted to oxaloacetate in the cytosol, completing the cycle of reactions. 

How do shuttle mechanisms differ from one another Two shuttle mechanisms—the glycerol—phosphate shuttle and the malate—aspartate shuttle—transfer the electrons, but not the NADH, produced in cytosolic reactions into the mitochondrion. In the hrst of the two shuttles, which is found in muscle and brain, the electrons are transferred to FAD in the second, which is found in kidney, hver, and heart, the electrons are transferred to NAD. With the malate-aspartate shuttle, 2.5 molecules of ATP are produced for each molecule of cytosolic NADH, rather than 1.5 ATP in the glycerol-phosphate shuttle, a point that affects the overall yield of ATP in these tissues. 

Synthesis of both progesterone and 17a-hydroxyprogesterone occurs in the endoplasmic reticulum from which these intermediates migrate to the mitochondrion, the location of the first reaction and the remainder of the pathways. The monooxygenases involved are all cytochrome P-450 enzymes but different electron-transport pathways transfer the electrons from NADPH to the... 

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