Cytochrome oxidase activity

The parasitic nematode, Ascaris suum, undergoes a number of well-characterized metabolic transitions during its development (Table 14.1), but little is known about the regulation of these events (Barrett, 1976 Komuniecki and Komuniecki, 1995). Adults reside in the porcine small intestine and fertilization takes place under low oxygen tensions. The unembryonated egg that leaves the host is metabolically quiescent, has no detectable cytochrome oxidase activity or ubiquinone and appears to be transcriptionally inactive (Cleavinger et al., 1989 Takamiya et al., 1993). Embryonation requires oxygen and after about 48-72 h is accompanied by... 

Copper deficiency in humans and other mammals is characterized by slow growth, hair loss, anemia, weight loss, emaciation, edema, altered ratios of dietary copper to molybdenum and other metals, impaired immune response, decreased cytochrome oxidase activity, central nervous system histopathology, decreased phospholipid synthesis, fetal absorption, and eventually death (NAS 1977 Gallagher 1979 Kirchgessner et al. 1979 USEPA 1980 ATSDR 1990 Percival 1995). 

Drinking water, 1000 mg KCN/L, exposure for 40 days Marked inhibition of cytochrome oxidase activity in liver, brain, and blood increased cyanide concentrations in all tissues inhibition of rhodanese activity diminished labile sulfur tissue levels 43... 

Ballantyne, B., S.P. Boardman, J. Bright, DJ. Coffee, T.D. Weber, and P. Williams. 1972. Tissue cyanide concentrations and cytochrome oxidase activities in experimental cyanide poisoning. Brit. Jour. Pharmacol. 44(2) 382P-383P. 

Tadic V. 1992. The in vivo effects of cyanide and its antidotes on rat brain cytochrome oxidase activity. Toxicology 76(l) 9-67. 

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. ... 

Lam, Y., and Nicholas, D. J. D. (1969). A nitrite reductase with cytochrome oxidase activity from Micrococcus denitrificans. Biochim. Biophys. Acta 180, 459-472. 

Copper was recognized as nutritionally essential by 1924 and has since been found to function in many cellular proteins.470-474 Copper is so broadly distributed in foods that a deficiency has only rarely been observed in humans.4743 However, animals may sometimes receive inadequate amounts because absorption of Cu2+ is antagonized by Zn2+ and because copper may be tied up by molybdate as an inert complex. There are copper-deficient desert areas of Australia where neither plants nor animals survive. Copper-deficient animals have bone defects, hair color is lacking, and hemoglobin synthesis is impaired. Cytochrome oxidase activity is low. The protein elastin of arterial walls is poorly crosslinked and the arteries are weak. Genetic defects in copper metabolism can have similar effects. 

In a study of the inhibition of components of the cytochrome systems by maeromolecular poly-ions, Person and Fine205-20 showed that such polycations as protamine sulfate, histone, and ribonuclease inhibit the cytochrome oxidase activity of various systems. The inhibition could be reversed by the addition- of poly-ions (and, especially, by polyglucose sulfate) the latter was also shown to inhibit the oxidase system reversibly. 

Moriguchi, K., Utsumi, M., Maeda, H., Kameyama, Y., and Ohno, N. 1999. Confocal laser scanning microscopic observation and cytochrome oxidase activity in the hamster submandibular gland using microwave irradiated fixation. Proc. Scanning 27 161-162. 

Active fish have a better developed capillary system in the red muscle to supply oxygen to the mitochondria, and a higher haematocrit (Blaxter et al., 1971). The red muscle tissue also contains more cytochromes (respiratory proteins), and exhibits more cytochrome oxidase activity, which is responsible for transferring electrons in die respiratory chain, more efficient respiration control (oxidative phosphorylation and P/O coefficient) and a greater Atkinson charge, which characterizes energy reserve accumulated in adenyl nucleotides ... 

Henriksson, J. and Reltman, J. S. (1977) Time course of changes In human skeletal muscle succinate dehydrogenase and cytochrome oxidase activities and maximal oxygen uptake with physical activity and inactivity. Acta Physiol. Scand. 99 91-7. 

Copper and Zinc in Aerobic Metabolism. Cytochrome oxidase, the terminal oxidase in the electron transport chain contains an atom of copper. On this enzyme the protons and electrons generated during oxidative metabolism combine with elemental oxygen to form water. During copper deficiency the tissue concentration of cytochrome oxidase is reduced. While the effects of lower cytochrome oxidase activity on exercise has not been described, it is likely that aerobic energy metabolism will be diminished. This effect of copper deficiency was first described in animals with myelin aplasls — the degeneration myelin (86). The oxidative process of phospholipid synthesis, a primary component of myelin, was depressed. Liver mitochondria had impaired respiratory activity (87). Cytochrome oxidase activity was also depressed in brain, heart and liver. 

Cardiovascular Disorders and Copper. Sudden cardiac failure has been associated with copper deficiency (91J. There are two attractive mechanisms. First, the coronary arteries and aorta may become weakened from an inability to synthesize elastin due to a decrease in lysyl oxidase activity. Rupture of these major blood vessels has been shown to cause sudden death in animals suffering from copper deficiency. Second, a decrease in cytochrome oxidase activity during copper deficiency Impairs aerobic metabolism of the heart and increases the risk of hypertrophy. Hypertrophy, which may lead to high output congestive heart failure, is exacerbated by hypochromic anemia also caused by copper deficiency. 

The level of another metabolite, formate, was also elevated in ALS and Hirayama patients. This metabolite is responsible for dismption of mitochondrial electron transport and energy production by inhibiting cytochrome oxidase activity. Cell death as a result of formate inhibition of cytochrome oxidase is believed to be the result of partial loss of ATP and, therefore, the loss of energy needed for basic cell functions. In addition, inhibition of cytochrome oxidase by formate can facilitate the production of cytotoxic reactive oxygen species, which also implies cell death. 

C-IO) Fumarase deficiency. There is a deficit in the transformation of fumarate to malate. The infant has developmental retardation, with abnormal neuromuscular function, lactic acidemia, and fumarate aciduria. The lactic acidosis may result from a backup of Krebs cycle function, all the way to lactate. Lactic acidosis may also be present in rare disorders of cytochrome oxidase activity. Diagnostically, there is a deficit in fumarase activity in assay of liver and skeletal muscle mitochondria. 

Hepatic mitochondria isolated from copper-deficient animals were found to be deficient in the cytochrome oxidase activity which correlated well with hem synthesis (57). Failure to synthesize hem from ferric iron and protoporphyrin could be enhanced by succinate or inhibited by cyanide, which suggests that the reduction from ferric to ferrous requires an intact electron transport system in order for hem synthesis to go into completion. 

Ballantyne, B. and Bright, J.E., Comparison of kinetic and end-point microdensitometry for the direct quantitative histochemical assessment of cytochrome oxidase activity, Histochem. J., 11,173-186, 1979. 

Saul RL, Kabir SH, Cohen Z, Bruce WR, Archer M (1981) Reevaluation of nitrate and nitrite levels in the human intestine. Cancer Res 41 2280-2283 Sawhney V, Nicholas DJD (1978) Sulphide-linked nitrite reductase from Thiobacillus denitrifi-cans with cytochrome oxidase activity purification and properties. J Gen Microbiol 106 119-128... 

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