Cytochrome muscle

As the temperature falls, the number, volume and enzymatic capacity of mitochondria in the muscle tissues of fish increase (Jankowski and Korn, 1965 Wodtke, 1974 Johnston and Maitland, 1980 Dunn, 1988) the sizes of liver cells and their nuclei also decrease (Campbell and Davis, 1978), while the number of muscle cytochromes increases (Sidell, 1977 Demin et al, 1989). Johnston and Home (1994) have shown that the proportion of each muscle fibre occupied by mitochondria in herring larvae is greater at lower... 

Treatment-related effects in men muscle lactate increased 33% (NS), muscle cytochrome oxidase decreased 16% (NS). 

Figure 2. The Influence of exercise intensity (treadmill running) on muscle cytochrome c content in the rat. Red vastus = fast-twitch red fiber section Soleus = slow-twitch red fiber section White vastus = fast-twitch white fiber section. "Reproduced with permission from Ref. 44. Copyright 1982, American Physiological Society. "...

Hickson, R. C. (1981) Skeletal muscle cytochrome c and myoglobin, endurance, and frequency of training, J. Appl. Physiol. Respirat. Environ, Exercise Physiol. 51 746-9, 1981,... 

Christensen E, Brandt NJ, Schmalbruch H, Kamieniecka Z, Hertz B, Ruitenbeek W. Muscle cytochrome c oxidase deficiency accompanied by a urinary organic acid pattern mimicking multiple acyl-Co A dehydrogenase deficiency. J Inherit Metab Dis 1993 16 553-6. 

The property of NO of inhibiting mitochondrial electron transfer was first recognized in 1994 by two British research groups [14, 15] that reported the inhibition of brain and muscle cytochrome oxidase (complex IV) activity by low NO concentrations in a reversible and Oj-competitive manner. More related to the scope of this review is the NO inhibition of electron transfer at complex III, ubiquinol-cytochrome c reductase, the second NO-sensitive point in the respiratory chain, where inhibition of electron transfer between cytochromes b and c enhances mitochondrial H2O2 production [16]. Nitric oxide, produced by NO donors or by mitochondrial nitric oxide synthase (mtNOS), inhibits complex III electron transfer and increases Oy and H2O2 production in sub-mitochondrial particles and in mitochondria. Complex IV is more sensitive to NO inhibition (IC5o=O.l pM) than complex III (IC5o=O.2 pM). 

Squid, T. rhombus Arm muscle Cytochrome oxidase I 250 Kitaura et al. (1998)... 

In Corynehacterium diphtheriae a hemoprotein which resembles cytochrome b is formed in large quantities when the organisms are grown in the presence of high concentrations of iron. The formation of hemoprotein parallels a decrease in the elaboration of toxin, and this has led to the suggestion that the toxin is the protein part of cytochrome b, or a precursor of it. The hemoprotein, obtained by sonic disruption of the bacterial cells, resembles heart muscle cytochrome b in its reduction by succinate. The reduced form reacts slowly with oxygen but is not oxidized by cytochrome c. 

A criterion for a substance to be a member of the respiratory chain is its ability to reactivate an enzymatic system from which this component has been removed. Such a system has been described by Nason and Lehman (1956), who used a rat skeletal muscle cytochrome c reductase inactivated by extraction with isooctane. In such a test vitamin E (Nason and Lehman, 1956) and vitamin K (Deul et ah, 1958) were found to be active. In an extensive study Weber et ah (1958a, b) showed, however, that this reactivation is not related to the redox system but to the isoprene-like side chain. Esterified tocopherol and the diacetates of the dihydro forms of vitamin Ki, Kj, and of ubiquinone(50) are as active as the free forms. Moreover, isolated side chains, such as phytol and squalene, showed exactly the same activity as the corresponding menadione derivatives, compared on a molar basis. The authors speculate that in this experiment a special function of the isoprene-like side chain, namely the binding of this vitamin to the fat material of the mitochondria, is demonstrated. 

One gram atom of iron was detected in each 67,000 gm. of the P. cytochrome oxidase sample, but copper was not found unlike in the muscle cytochrome a preparation. The nitrogen content was 16.3%. 

Deficient activity of muscle cytochrome c oxidase has also been reported in a patient with a mitochondrial myopathy associated with chronic lactic acidaemia, growth failure and nerve deafness (Monnens etaL, 1975) and in a patient with subacute necrotizing encephalomyelopathy (Leigh s disease)... 

Fatal infantile cytochrome c oxidase (CCO) deficiency is characterized by total absence of catalytic activity in skeletal muscle. This often occurs within the context of the Fanconi syndrome, or less commonly in association with a cardiomyopathy. Although the deficiency is global in skeletal muscle, with all fibers affected, only isolated scattered fibers show abnormal aggregations of mitochondria (ragged-red fibers). Multiple affected siblings within one family are frequently encountered and suggest autosomal recessive inheritance. The condition normally proves fatal before the age of six months and is characterized by worsening intractable lactic acidemia. 

Figure 13. Mosaic of cytochrome oxidase-deficient muscle fibers (asterisks) in a patient with KSS and a heteroplasmic mtDNA deletion.

Under anaerobic conditions, p,p -DDT is converted to p,p -DDD by reductive dechlorination, a biotransfonnation that occurs postmortem in vertebrate tissues such as liver and muscle and in certain anaerobic microorganisms (Walker and Jefferies 1978). Reductive dechlorination is carried out by reduced iron porphyrins. It is carried out by cytochrome P450 of vertebrate liver microsomes when supplied with NADPH in the absence of oxygen (Walker 1969 Walker and Jefferies 1978). Reductive dechlorination by hepatic microsomal cytochrome P450 can account for the relatively rapid conversion of p,p -DDT to p,p -DDD in avian liver immediately after death, and mirrors the reductive dechlorination of other organochlorine substrates (e.g., CCI4 and halothane) under anaerobic conditions. It is uncertain to what extent, if at all, the reductive dechlorination of DDT occurs in vivo in vertebrates (Walker 1974). 

In vivo, patients treated with AZT develop a mitochondrial myopathy with mitochondrial DNA depletion, deficiency of cytochrome c oxidase (complex IV), intracellular fat accumulation, high lactate production and marked phosphocreatine depletion (Lewis and Dalakas 1995 Dalakas 2001). Clinically, the patient presents with fatigue, myalgia, muscle weakness, wasting and elevated serum creatine kinase. Muscle biopsy shows ragged red fibers , the characteristic histopathologic changes of mitochondrial myopathy, cansed by subsarcolemmal accumulation of mitochondria (Lewis and Dalakas 1995). 

Cytochrome c is a heme containing protein which occurs in muscle at lower concentrations than does myoglobin. It was demonstrated some time ago (18) that oxidized cytochrome c reacts with gaseous nitrite oxide to produce a nltrosyl compound. Recent work (19, 20, 21) has examined the reactions of cytochrome c with nitrite and the contribution of the product formed to cured meat color in considerably more detail. The general conclusion is that even at the pH normally encountered in meat, the reaction can take place in the presence of ascorbic acid but probably does not affect meat color because of the unstable nature of the reaction product and the low concentration. 

In a subsequent study Bhambhani et al. (1997) observed significant increases in blood lactate concentrations in male and female volunteers exposed to 10 ppm hydrogen sulfide, although there was not a significant change in the activities of muscle lactate dehydrogenase, citrate synthase, or cytochrome oxidase. 

Mei, B., Komuniecki, R. and Komuniecki, P.R. (1997) Localization of cytochrome oxidase and the 2-methyl branched-chain enoyl CoA reductase in muscle and hypodermis of Ascaris suum larvae and zdults. Journal of Parasitolog 83, 760-763. 

Abnormalities of the respiratoiy chain. These are increasingly identified as the hallmark of mitochondrial diseases or mitochondrial encephalomyopathies [13]. They can be identified on the basis of polarographic studies showing differential impairment in the ability of isolated intact mitochondria to use different substrates. For example, defective respiration with NAD-dependent substrates, such as pyruvate and malate, but normal respiration with FAD-dependent substrates, such as succinate, suggests an isolated defect of complex I (Fig. 42-3). However, defective respiration with both types of substrates in the presence of normal cytochrome c oxidase activity, also termed complex IV, localizes the lesions to complex III (Fig. 42-3). Because frozen muscle is much more commonly available than fresh tissue, electron transport is usually measured through discrete portions of the respiratory chain. Thus, isolated defects of NADH-cytochrome c reductase, or NADH-coenzyme Q (CoQ) reductase suggest a problem within complex I, while a simultaneous defect of NADH and succinate-cytochrome c reductase activities points to a biochemical error in complex III (Fig. 42-3). Isolated defects of complex III can be confirmed by measuring reduced CoQ-cytochrome c reductase activity. 

Myopathies have been described in several sporadic cases with lactic acidosis, cytochrome oxidase (COX)-positive RRF in muscle, and isolated complex I deficiency, and have been attributed to various pathogenic mutations in ND genes. The sporadic nature of these myopathies suggests that the ND mutations are de novo, arising spontaneously in myogenic stem cells after germ-layer differentiation (somatic mutations) [14]. 

Defects of complex II. These have not been fully characterized in the few reported patients, and the diagnosis has often been based solely on a decrease of succinate-cytochrome c reductase activity (Fig. 42-3). However, partial complex II deficiency was documented in muscle and cultured fibroblasts from two sisters with clinical and neuroradiological evidence of Leigh s syndrome, and molecular genetic analysis showed that both patients were homozygous for a point mutation in the flavoprotein subunit of the complex [17]. This was the first documentation of a molecular defect in the nuclear genome associated with a respiratory chain disorder. 

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