Metabolism electron transport

An example of oxidative cross-linking takes place during vancomycin biosynthesis three cytochrome P450 enzymes—which use the same heme cofactor as the cytochromes from the primary metabolic electron transport chain—cross-link aromatic rings in its scaffold to form its rigid cup-like shape (29, 30). 

Ketone-body metabolism Electron-transport chain and p ho s phate - transfe r enzymes... 

Situated as it is between glycolysis and the electron transport chain, the TCA cycle must be carefully controlled by the ceil. If the cycle were permitted to run unchecked, large amounts of metabolic energy could be wasted in overproduction of reduced coenzymes and ATP conversely, if it ran too slowly, ATP would not be produced rapidly enough to satisfy the needs of the cell. Also, as just seen, the TCA cycle is an important source of precursors for biosynthetic processes and must be able to provide them as needed. 

The processes of electron transport and oxidative phosphorylation are membrane-associated. Bacteria are the simplest life form, and bacterial cells typically consist of a single cellular compartment surrounded by a plasma membrane and a more rigid cell wall. In such a system, the conversion of energy from NADH and [FADHg] to the energy of ATP via electron transport and oxidative phosphorylation is carried out at (and across) the plasma membrane. In eukaryotic cells, electron transport and oxidative phosphorylation are localized in mitochondria, which are also the sites of TCA cycle activity and (as we shall see in Chapter 24) fatty acid oxidation. Mammalian cells contain from 800 to 2500 mitochondria other types of cells may have as few as one or two or as many as half a million mitochondria. Human erythrocytes, whose purpose is simply to transport oxygen to tissues, contain no mitochondria at all. The typical mitochondrion is about 0.5 0.3 microns in diameter and from 0.5 micron to several microns long its overall shape is sensitive to metabolic conditions in the cell. 

As we have seen, the metabolic energy from oxidation of food materials—sugars, fats, and amino acids—is funneled into formation of reduced coenzymes (NADH) and reduced flavoproteins ([FADHg]). The electron transport chain reoxidizes the coenzymes, and channels the free energy obtained from these reactions into the synthesis of ATP. This reoxidation process involves the removal of both protons and electrons from the coenzymes. Electrons move from NADH and [FADHg] to molecular oxygen, Og, which is the terminal acceptor of electrons in the chain. The reoxidation of NADH,... 

The third reaction of this cycle is the oxidation of the hydroxyl group at the /3-position to produce a /3-ketoacyl-CoA derivative. This second oxidation reaction is catalyzed by L-hydroxyacyl-CoA dehydrogenase, an enzyme that requires NAD as a coenzyme. NADH produced in this reaction represents metabolic energy. Each NADH produced in mitochondria by this reaction drives the synthesis of 2.5 molecules of ATP in the electron transport pathway. L-Hydroxyacyl-... 

Complexes III and IV have Fe-porphyrin prosthetic groups (hemes), complex IV also contains copper atoms which are involved in electron transport. Complexes I, III, and IV use the energy of electron transport to pump protons out of the matrix so as to maintain a pH gradient and an electrical potential difference across the inner membrane required for ATP synthesis (see below and Appendix 3). It is important to remember that all dehydrogenations of metabolic substrates remove two protons as well as two electrons and that a corresponding number of protons are consumed in the final reduction of dioxygen (Figures 5, 6). 

Hydrogen sulfide inhibits mitochondrial cytochrome oxidase, resulting in disruption of the electron transport chain and impairing oxidative metabolism. Nervous and cardiac tissues, which have the highest oxygen demand (e.g., brain and heart), are especially sensitive to disruption of oxidative metabolism (Ammann 1986 Hall 1996). 

Oxidation is intimately linked to the activation of polycyclic aromatic hydrocarbons (PAH) to carcinogens (1-3). Oxidation of PAH in animals and man is enzyme-catalyzed and is a response to the introduction of foreign compounds into the cellular environment. The most intensively studied enzyme of PAH oxidation is cytochrome P-450, which is a mixed-function oxidase that receives its electrons from NADPH via a one or two component electron transport chain (10. Some forms of this enzyme play a major role in systemic metabolism of PAH (4 ). However, there are numerous examples of carcinogens that require metabolic activation, including PAH, that induce cancer in tissues with low mixed-function oxidase activity ( 5). In order to comprehensively evaluate the metabolic activation of PAH, one must consider all cellular pathways for their oxidative activation. 

In the presence of the inhibitor rotenone (to prevent the oxidation of NADH by the electron transport chain), succinate can be metabolized only to fumarate, producing an FADH2 in the process. 

In the absence of rotenone, the NADH that is made from the conversion of succinate to oxaloacetate can be oxidized by the electron transport chain. The metabolism of succinate then becomes... 

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