Mitochondrial cytochrome system

Mitochondrial cytochrome P450 systems are found in steroidogenic tissues such as adrenal cortex, testis, ovary, and placenta and are concerned with the biosyn-... 

Miki H, Takeuchi H, Yamada A, Nishioka M, Matsuzawa Y, et al. 1986. Quantitative analysis of the mitochondrial cytochrome P-450-linked monooxygenase system NADPH-hepatoredoxin reductase, hepatoredoxin, and cytochrome P-450s27 in livers of patients with cerebrotendinous xanthomatosis. Clin Chim Acta 160 255-263. 

Most cases of intoxication from industrial exposure have been mild, with rapid onset of eye irritation, headache, sneezing, and nausea weakness, light-headedness, and vomiting may also occur. Acute exposure to high concentrations may produce profound weakness, asphyxia, and death. Acrylonitrile is metabolized to cyanide by hepatic microsomal reactions. Deaths from acute poisoning result from inhibition of mitochondrial cytochrome oxidase activity by metabolically liberated cyanide. Inhalation of more moderate concentrations for a longer period of time leads to damage to the liver tissues in addition to central nervous system (CNS) effects. ... 

Another property that distinguishes various cytochromes is the redox potential E ° (Table 6-8), which in this discussion is given for pH 7.0. Cytochromes carry electrons between other oxidoreductase proteins of widely varying values of E°. Because of the various heme environments cytochromes have greatly differing values of E°, allowing them to function in many different biochemical systems. 97a/97b For mitochondrial cytochrome c the value of E ° is + 0.265 V but for the closely related cytochrome/of chloroplasts it is +0.365 V and for cytochrome c3 of Desulfovibrio about -0.330 V. There is more than an 0.6-volt difference between E ° ... 

As might be expected, such an unusual compound has been the subject of intense biochemical study over the years. It is closely associated with the function of the cytochrome oxidase in the inner mitochondrial electron system. An introduction to this field of endeavor can be gained from publications by Robinson et al. (1990) and by Hoch (1992). 

The crystal structure of NADPH-cytochrome P450 reductase (CPR), the common electron-transfer protein of Class 11 eukaryotic P450 systems, was reported in 1997. This was followed by the structures of adrenodoxin reductase (AdR) and adrenodoxin (Adx), the two electron-transfer proteins of the Class 1 mitochondrial P450 system. The crystal structure of a cross-linked AdR-Adx complex has also been reported. " Putidaredoxin reductase (PdR) and putidaredoxin (Pd) of the P450cam system have also been structurally characterized. ... 

Adiponitrile s mechanism of toxicity is similar to cyanide because it can potentially liberate cyanide in the body spontaneously. It forms a stable complex with ferric iron in the cytochrome oxidase enzymes, thereby inhibiting cellular respiration. Cyanide affects primarily the central nervous system (CNS), producing early stimulation followed by depression. It initially stimulates the peripheral chemoreceptors (causing increased respiration) and the carotid bodies (thereby slowing the heart). Early CNS, respiratory, and myocardial depression result in decreased oxygenation of the blood and decreased cardiac output. These effects produce both stagnation and hypoxemic hypoxia in addition to cytotoxic hypoxia from inhibition of mitochondrial cytochrome oxidase. 

The terminal oxidase in an energy-transducing, cytochrome-based electron-transport system maintains electron flow by coupling cytochrome oxidation to dioxygen (O2) reduction. Members of this protein class are referred to as cytochrome oxidases they carry out Oj-binding and redox chemistry at transition metal-containing active sites. Although iron is the most commonly used metal and may occur as a protoheme or iron-chlorin species in the protein, this section is concerned only with mitochondrial cytochrome oxidase, which contains 2 mol of Cn and 2 mol of heme a bound Fe per function unit. Biochemistry of the protein will not be considered here, instead the focus will be on the stmcture of the metal centers, on the reactions they catalyze and on models for these centers. 

The turnover numbers found for 26-hydroxylation in the reconstituted system were 50-200 times higher than those reported for reconstituted systems from microsomes and it was concluded that the mitochondrial cytochrome P-450 has a much higher potential for 26-hydroxylation than the microsomal cytochrome P-450 [133]. 

Type b Cytochromes Reported to Exist in Mitochondrial Respiratory Systems in Addition to Classic Cytochrome b (6k)... 

The name cytochrome fei has been used for the bacterial type b cytochromes having the a band near 560 nm since its designation by Keilin (193). However, this name is now usually applied in a limited sense to the cytochromes with a band at 558 or 559 nm in the nitrate reductase (nitrate respiration) system, which is a more primitive form of respiration than the mitochondrial respiration system. 

N.G. Avadhani (1984). Hepatic mitochondrial cytochrome P-450 system Distinctive features of cytochrome P-450 involved in the activation of afla-toxin B and benzo(a)pyrene. J. Biol. Chem. 259, 12495-12501. 

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