Cytochrome oxidase carbon monoxide effect

The electron transport chain is vital to aerobic organisms. Interference with its action may be life threatening. Thus, cyanide and carbon monoxide bind to haem groups and inhibit the action of the enzyme cytochrome c oxidase, a protein complex that is effectively responsible for the terminal part of the electron transport sequence and the reduction of oxygen to water. 

Whether the toxic effects are mainly due to anemic hypoxia or to the histotoxic effects of carbon monoxide on tissue metabolism is a source of controversy. Carbon monoxide will certainly bind to myoglobin and cytochromes such as cytochrome oxidase in the mitochondria and cytochrome P-450 in the endoplasmic reticulum, and the activity of both of these enzymes is decreased by carbon monoxide exposure. However, the general tissue hypoxia will also decrease the activity of these enzymes. 

The answer is c. (Murray, pp 123-148. Scriver, pp 2367-2424. Sack, pp 159-175. Wilson, pp 287-317.) The electron transport chain shown contains three proton pumps linked by two mobile electron carriers. At each of these three sites (NADH-Q reductase, cytochrome reductase, and cytochrome oxidase) the transfer of electrons down the chain powers the pumping of protons across the inner mitochondrial membrane. The blockage of electron transfers by specific point inhibitors leads to a buildup of highly reduced carriers behind the block because of the inability to transfer electrons across the block. In the scheme shown, rotenone blocks step A, antimycin A blocks step B, and carbon monoxide (as well as cyanide and azide) blocks step E. Therefore a carbon monoxide inhibition leads to a highly reduced state of all of the carriers of the chain. Puromycin and chloramphenicol are inhibitors of protein synthesis and have no direct effect upon the electron transport chain. 

The second type of asphyxiants is that which works at the cellular level. Here, they interfere with the mitochondrial cytochrome oxidase s function in the electron transport chain. Because this is the fuel cell for the body, energy production ceases within the cell, with cell death following close behind. The key substance implicated here is cyanide, which is usually found only in a chemical laboratory setting, but can also be a side effect of smoke inhalation. As previously mentioned, hydrogen sulfide and carbon monoxide also have some effect at this site. In addition, azides are cellular asphyxiants. The azides, along with the nitro-ate-ites, are also vasodilators and can cause headaches and hypotension. 

ORD measurements in the Soret region of the carbon monoxide derivative of cytochrome oxidase showed a single Cotton effect near 430 nm, which indicated that only cytochrome a3 has an optically active transition, while the non-reacting cytochrome a subunit did not show measurable optical activity (249). By comparison of oxidation-reduction... 

This compound, similar to glycer-aldehyde, pyruvate, and alpha-ketoglutarate, trapped cyanide to form cyanohydrin, thus rapidly reactivating the enzyme cytochrome oxidase and restoring CN-inhibited mitochondrial respiration. The authors have reported this antidote to be effective especially in cases of CN-carbon monoxide smoke inhalation. 

Cyanide, azide or carbon monoxide, all of which bind irreversibly to the iron of cytochrome a, and thus inhibit complex IV Again these compounds inhibit oxidation of malate and succinate, as both rely on cytochrome oxidase, and again the addition of the uncoupler has no effect. 

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