Mitochondrial inhibitor carbon monoxide

Most of these studies have established that the enzyme is located in the mitochondrial fraction of tissue homogenates, although the enzyme in the fat body and Malpighian tubules of Locusta is reportedly associated with the microsomal fraction (30). All studies concur that the enzyme is a cytochrome P-450-mediated mixed-function oxidase and its requirements for NADPH and 02 and sensitivity to inhibitors such as carbon monoxide, metyrapone, etc., support this conclusion. As yet, there are no reports as to whether the enzyme is associated with an iron sulfur protein similar to the adrenodoxin of the mammalian mitochondrial steroid... 

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 movement of electrons through the electron carrying proteins of the inner mitochondrial membrane is shown in Figure 15.9. Also shown are inhibitors of electron movement at their point of action and the sites where artificial electron acceptors can accept electrons from the electron transport system. Specific inhibitors shown in Figure 15.9 are rotenone, amytal, antimycin A, cyanide, azide, and carbon monoxide. The artificial electron acceptors are methylene blue, phenazine methosulfate, 2,6-indophenol, tetramethyl-p-phenylene diamine, and ferricyanide. 

Wyatt CN, Buckler KJ. The effect of mitochondrial inhibitors on membrane currents in isolated neonatal rat carotid body type I cells. J Physiol Lond 2000 527 121P-122P. Buerk DG, Chugh DK, Osanai S, Mokashi A, Lahiri S. Dopamine increases in cat carotid body during excitation by carbon monoxide implications for a chromophore theory of chemoreception. J Auton Nerv Syst 1997 67 130-136. 

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