Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:1.9.3.1 (cytochrome oxidase)
8,822 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A female child suffering from intrauterine growth retardation was born by caesarean section at 32 weeks. In the immediate newborn period there was a metabolic acidosis but this resolved. Hypotonia, muscular weakness and poor respiratory effort were evident and the child died at 6 days of age. A previous male sibling had died at 3 months of age after similar symptoms with seizures and a dysmyelination disorder. Post-mortem examination of both children showed damage to the basal ganglia. Defects in the activities of the pyruvate dehydrogenase complex, cytochrome oxidase and succinate cytochrome c reductase were found in cultured skin fibroblasts. Similar defects were found in isolated muscle mitochondria but not in isolated liver mitochondria from the patient. Immunoblotting for cytochrome oxidase showed that the multienzyme complex was not assembled in muscle and skin fibroblast mitochondria, but was assembled in liver mitochondria. Similar results were obtained in cultured skin fibroblast mitochondria for complex I of the mitochondrial respiratory chain. This is the first occasion that multiple defects have been demonstrated both in tissue and in culture skin fibroblasts in mitochondrial respiratory chain complexes.
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PMID:Fatal combined defects in mitochondrial multienzyme complexes in two siblings. 132 97

The method of blood-free isolated perfused rat brain was described, of which EEG was within the normal range. The simultaneous measurement of heme a+a3 and copper in cytochrome oxidase could be performed under the various conditions such as graded hypoxia and seizure. The relationship between these two chromophores in the brain was same to that of isolated mitochondria.
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PMID:Brain oxygenation state: preparation of isolated perfused rat brain and near-infrared spectrophotometry. 133 47

Fourteen new cases of cytochrome oxidase (COX)-associated Leigh syndrome (LS) are combined with 20 reported cases to describe the clinical, laboratory, and radiological features of this devastating metabolic condition. Three clinical stages are identified. Most patients have normal neurological development during the first 8-12 months (stage I). Somatic complaints are common, including chronic diarrhea, recurrent vomiting, anorexia, and decelerating body and head growth. The second stage evolves during late infancy and early childhood when motor regression becomes evident. Eye signs, altered breathing patterns, pyramidal, extrapyramidal, and cerebellar signs emerge and sudden clinical deterioration occurs during intercurrent infectious or metabolic stress. The last stage may extend from 2 to 10 years and is manifested by extreme hypotonia, swallowing difficulties and undernutrition. Feeding assistance is necessary and seizures may occur. The CSF lactate concentration is consistently elevated and MRI abnormalities are seen in the subcortical structures. COX deficiency affects most tissues, but is not always generalized. For example, 3 patients with a cardiomyopathy had normal COX activity in cultured skin fibroblasts. Nearly normal amounts of cross-reacting material are present by ELISA and immunoblot analyses. Parental consanguinity has been found in several families, the hereditary pattern is recessive and males are affected more commonly (2:1). The biomolecular abnormality causing COX deficiency in LS is unknown, but the available evidence implicates a nuclear-encoded protein that affects the structure or the stability of the holoenzyme complex.
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PMID:Cytochrome c oxidase-associated Leigh syndrome: phenotypic features and pathogenetic speculations. 165 84

Focal cortical CBF and oxygenation were measured in rats during repetitive seizures to determine whether CBF is maintained above a critical level for adequate delivery of O2. Cerebral oxygenation was determined by measuring relative changes in the oxidation/reduction level of cytochrome aa3 and CBF was measured by the washout of H2. During early seizures, cortical CBF increased to 350% of control and cortical oxygenation also rose markedly. During later seizures, both the increases in CBF and in cortical oxygenation were attenuated progressively. This was accompanied also by attenuation of the associated increases in MABP. Cortical oxygenation decreased during a seizure if the increase in CBF failed to exceed 150-200% of control, defining the critical CBF value. Ventilating the rats on 97% O2 resulted in restoration of the seizure-associated increases in cortical oxygenation in 50% of the cases. The elevation of inspired O2 was effective only if CBF increased once again above 150-200% of control, confirming that the critical CBF lies within this range of values. We conclude that CBF must rise greater than 200% of control levels to provide sufficient O2 to meet the enhanced metabolic requirements of repetitive seizures.
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PMID:Relative hypoperfusion in rat cerebral cortex during recurrent seizures. 184 66

Sodium azide is a chemical of rapidly growing commercial importance with a high acute toxicity and an unknown mechanism of action. Although it has some chemical properties and biological effects in common with cyanide, its lethality does not appear to be due to inhibition of cytochrome oxidase. Unlike cyanide it is a potent vasodilator and inhibitor of platelet aggregation presumably by virtue of its conversion to nitric oxide in vivo and in isolated preparations of blood vessels and thrombocytes. It is not clear whether the high toxicity of azide is due to nitric oxide or to the parent anion. Of a number of possible azide antagonists tested in intact mice only phenobarbital in both anesthetic and subanesthetic doses afforded statistically significant protection against death. Diazepam, phenytoin, and an anesthetic dose of a ketamine/xylazine combination had no effect. Major motor seizures are sometimes seen in human azide poisoning, and these are a regular feature of azide poisoning in laboratory rodents. Solutions of nitric oxide given systemically to mice produced no signs of toxicity, but doses 1,000-fold lower placed in the cerebroventricular system of rats produced brief but violent tonic convulsive episodes. A dose of 0.61 mmol/kg azide as given systemically regularly produced convulsions whereas a dose of 6 mumol/kg given icv produced seizures in rats. The icv convulsive dose of azide was 50-fold larger than the icv dose of nitric oxide. These results suggest that azide lethality is due to enhanced excitatory transmission in the central nervous system perhaps after its conversion to nitric oxide.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Acute neurotoxicity of sodium azide and nitric oxide. 191 70

Hyperglycemic, but not normoglycemic cats exposed to anoxia develop neurologic signs following reoxygenation including fasciculations, focal and tonic-clonic seizures and coma after a symptom-free period. These symptomatic hyperglycemic cats may develop brain edema and will show diffuse neuronal injury or brain infarction depending on length of survival. Brain mitochondria isolated from symptomatic but not asymptomatic cats have decreased ADP- and uncoupler-stimulated oxygen consumption rates. Since impaired respiration could result from altered electron transport chain function, we measured cytochrome c, b, and aa3 concentrations and the activities of the five electron transfer complexes in isolated brain mitochondria. In symptomatic cats marked alterations were present in particular in complex IV, cytochrome oxidase, with a 57% reduction in activity and a 45% reduction in prosthetic group (cytochrome aa3) concentrations. Less marked reductions in other segments of the chain included 27% and 41% decreases, respectively, in cytochrome c concentrations and in electron transfer complex II, succinate:ubiquinone oxidoreductase activity. Cytochrome b concentrations and complex I, II and V activities were unchanged. Small but significant decreases in cytochrome aa3 concentrations (18%) and cytochrome oxidase activity (20%) were also present in mitochondria from postanoxic hyperglycemic cats prior to appearance of neurologic signs. These results indicate that delayed decreases in the activities of specific electron transfer complexes are correlated with impaired mitochondrial respiration and neurologic deterioration in postanoxic hyperglycemic cats. However, it is presently unclear if these postanoxic brain mitochondrial alterations are primary or secondary events in the development of brain injury.
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PMID:Delayed decreases in specific brain mitochondrial electron transfer complex activities and cytochrome concentrations following anoxia/ischemia. 208 31

We previously demonstrated markedly inhibited brain mitochondrial respiration only in cats that (a) were hyperglycemic at anoxia and (b) had neurologic signs, i.e., fasciculations in tongue or facial muscles or focal seizures following reoxygenation. However, since the relationship between time of onset of mitochondrial dysfunction and neurologic signs was unclear, in the present study we killed postanoxic cats immediately when signs first appeared. Cerebrocortical homogenates and isolated brain mitochondria only from symptomatic cats showed markedly inhibited substrate-, ADP-, and uncoupler-stimulated respiration rates. Cytochrome oxidase activity and cytochrome aa3 concentrations were also markedly reduced in these mitochondria. Since brain mitochondrial function was impaired when neurologic signs first appeared, mitochondrial alterations are an important early organellar change correlated with development of neurologic deterioration following anoxia.
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PMID:Delayed onset of neurologic deterioration following anoxia/ischemia coincides with appearance of impaired brain mitochondrial respiration and decreased cytochrome oxidase activity. 215

Nonsynaptic mitochondria isolated from rat brain hippocampus were compared with those obtained by means of the same preparative procedure from cerebral cortex and striatum. Protein recovery, marker enzyme activities (lactate dehydrogenase, citrate synthase, and acid phosphatase), state 4 respiration, and response to hypoosmotic shock showed no difference among the three cerebral regions, suggesting homogeneous behavior during the subfractionation procedure. Cholinergic markers--choline acetyltransferase, acetylcholinesterase activities, and high-affinity choline uptake--evaluated on synaptosomes showed the classic regional pattern with an enrichment in the striatum (striatum much greater than hippocampus). The coupling state of the mitochondrial fractions was maintained (respiratory control ratios ranging from 3.62 to 5.08 with glutamate + malate as oxidizable substrates), showing a metabolic competence sufficient to perform metabolic studies. Regional differences were found in state 3, uncoupled state of respiration, and cytochrome oxidase activity. Hippocampus showed the lower values (hippocampus less than striatum less than cortex). A possible role of this lower capacity of mitochondrial energy metabolism in determining the sensitivity of hippocampal neurons to ischemia or epileptic seizures is suggested.
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PMID:Oxidative metabolism of nonsynaptic mitochondria isolated from rat brain hippocampus: a comparative regional study. 283 1

A 2-month-old boy had progressive generalized weakness, hypotonia, and respiratory insufficiency requiring assisted ventilation. At age 3 1/2 months, he started having seizures and recurrent pulmonary infections; he died at age 7 months. Serum lactate was chronically elevated, but there was no aminoaciduria. Histochemical and ultrastructural studies of muscle biopsies at ages 2 and 3 months showed excessive mitochondria, lipid, and glycogen; a third biopsy at 6 months showed marked increase in perimysial fibrous and fat tissue. Cytochrome c oxidase activity was 7% of normal in the first biopsy and undetectable in the others. Cytochrome spectra of mitochondria isolated from postmortem muscle showed complete lack of cytochrome aa3. Antibodies were obtained against cytochrome c oxidase purified from normal human heart. Immunotitration and enzyme-linked immunosorbent assay (ELISA) showed decreased immunologically reactive enzyme protein in the patient's muscle, but SDS-PAGE electrophoresis of immunoprecipitates of muscle mitochondrial extracts showed the presence of all cytochrome c oxidase subunits. These data suggest that decreased synthesis of one or more subunits may result in markedly decreased concentration of electrophoretically normal complex IV in skeletal muscle.
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PMID:Fatal infantile cytochrome c oxidase deficiency: decrease of immunologically detectable enzyme in muscle. 298 57

Cerebral partial pressure of O2 (PO2), relative changes in the ratio of reduced/oxidized cytochrome aa3, blood flow, and the arteriovenous difference in O2 content were measured during seizures with and without pulmonary edema. Seizures were induced with bicuculline (0.2-1.2 mg/kg iv) in rats anesthetized with 70% N2O and paralyzed with curare. Briefer seizures were accompanied by increased cerebral PO2 and increased oxidation of cytochrome aa3. Lung water content and arterial O2 partial pressure (PaO2) remained normal. Longer duration seizures were also accompanied initially by increases in cerebral oxygenation. Within minutes, however, PaO2 fell from a mean of 118 to 51 mmHg, and lung water content increased from 76.2 to 83.6%. Cerebral PO2 fell but most often rose back to or above control levels, while cytochrome aa3 became markedly reduced. Simultaneously, cerebral blood flow increased more than 300% above preseizure values and O2 delivery increased more than O2 consumption. The reductive shift of cytochrome aa3 was greater than that produced by lowering PaO2 to equivalent values in seizure-free rats. The reductive shift of cytochrome aa3, despite increased O2 delivery, may be indicative of derangements in cerebral O2 diffusion or energy metabolism.
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PMID:Seizure-associated pulmonary edema and cerebral oxygenation in the rat. 355 25


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