Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.9.3.1 (cytochrome oxidase)
 8,822 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Homotypic fetal neurons were transplanted into previously lesioned ventrobasal complex of rats. After 1-3 months of survival the animals received injections of 2-deoxy-[14C]glucose to reveal metabolic activity of the transplanted cells in response to somatic stimuli. These experiments indicated that stimulus-evoked activity in the transplants of animals receiving a somatic stimulus was significantly greater than in the transplants of animals that were not stimulated. Control studies using cell counts, cytochrome oxidase and acetylcholinesterase histochemistry established that the differences in activity values were not due to the number of surviving cells or the metabolic health of the individual grafts.
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PMID:Somatic activation of thalamic neurons transplanted into lesioned somatosensory thalamus. 253 4

Since the inception of the 14C-deoxyglucose method and its extension to in vivo imaging of regional cerebral glucose metabolism in humans by positron emission tomography, uncertainty has persisted concerning the type of work to which regional metabolism is coupled, as well as the distribution of this work within the neuron. 14C-deoxyglucose studies indicate that functionally-coupled neural metabolism is more apparent in axon terminals and perhaps dendrites than neuronal perikarya. Moreover, it appears that most of the metabolism in axon terminals is accounted for by Na+-K+-ATPase activity. Nevertheless, cytochrome oxidase histochemistry reveals the presence of intensely reactive mitochondria in soma-dendrite regions opposite presynaptic axon terminals, thereby indicating that continuous temporal and spatial summation of postsynaptic graded potentials is associated with increased metabolism. While the situation concerning the relative postsynaptic metabolic prices of EPSP's and IPSP's remains uncertain, the presence of elevated levels of cytochrome oxidase activity within certain classes of presynaptic terminals indicates that active excitation and inhibition is associated with increases in presynaptic metabolism. This observation has been confirmed in 14C-deoxyglucose studies. Nevertheless, studies of neonatal hippocampus indicate that, before metabolic activity shifts to dendritic and telodendritic regions of electrophysiological activity, metabolism is high in somal foci of biosynthesis.
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PMID:The relationship between CNS metabolism and cytoarchitecture: a review of 14C-deoxyglucose studies with correlation to cytochrome oxidase histochemistry. 253 21

Stable-isotope tracer experiments performed in vitro are evaluated for their utility in differentiating between pyruvate dehydrogenase and cytochrome oxidase deficiencies, two of several enzyme defects commonly associated with the lactic acidemias. Fibroblasts of enzyme-deficient individuals and of age-matched controls are grown in medium containing [U-13C]glucose. Direct analysis of cells and conditioned culture medium provides only minor differences in the organic acid/amino acid GC-MS profiles, making differentiation of enzyme defects difficult by this method. However, differences have been found in the glucose turnover into various cell metabolites, making differentiation of these two enzyme defects possible. The cellular pool of glutamic acid experiences 13C-enrichment in both the control and cytochrome oxidase deficient lines, but not in the pyruvate dehydrogenase-deficient line. The cellular pool of an unknown, possibly an aminopentose sugar, on the other hand, experiences 13C-enrichment in the pyruvate dehydrogenase and control lines, but not in the cytochrome oxidase line. These observations, as well as other differences in the extent of enrichment into various metabolite pools, suggest that this stable-isotope approach, in vitro, is feasible and may allow these two enzyme defects to be differentiated in a definitive manner. Such stable-isotope experiments are easy to carry out with cultured cells and are inexpensive. Applications of the technique to other genetic disorders might be appropriate.
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PMID:Determination of [U-13C]glucose turnover into various metabolite pools for the differential diagnosis of lactic acidemias. 254 11

Mutations that define the ctaA gene of Bacillus subtilis block cytochrome aa3 formation and sporulation. We have recently described the isolation and initial characterization of the ctaA locus. Analysis of in vivo mRNA transcripts by RNase protection experiments located the 5' and 3' termini of the ctaA transcript, confirming a monocistronic structure. By using a nuclease protection assay, an increase in the abundance of steady-state ctaA mRNA was observed during the initiation of sporulation, followed by a decrease during subsequent stages. Transcripts originating from the ctaA gene were most abundant 2.0 h after the end of exponential growth. This pattern of ctaA mRNA accumulation was confirmed by coupling the transcription of the ctaA gene to lacZ in an integrative plasmid vector. Expression of ctaA was not repressed by glucose and was independent of the spoOA and spoOH (sigH) gene products. Postexponential expression was found to be dependent on the product of the strC gene. The expression of ctaA appears to be regulated in a growth stage-specific manner. The transcriptional start site, identified by high-resolution S1 nuclease protection experiments, was preceded by a single sigma A-dependent promoter sequence.
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PMID:Structure and expression of the cytochrome aa3 regulatory gene ctaA of Bacillus subtilis. 254 7

Oxygen consumption and 3H-guanosine diphosphate (GDP) binding were determined in brown adipocytes and mitochondria from 28-day gestation fetuses of alloxan-diabetic rabbit does and saline-injected controls. Maternal diabetes was classified as severe or mild determined by whether maternal blood glucose values were greater or less than 200 mg/dL, respectively, at death. Basal oxygen consumption and adipocyte diameters did not vary among groups. A significant reduction in maximal norepinephrine (NE) stimulated O2 consumption by fetal brown adipose tissue (BAT) cells was seen in offspring of severely diabetic pregnancies when compared with control values (248 +/- 53 +/- v482 +/- 32 microL O2/10(6) cells/h; P less than .005). In contrast, a significant increase in maximal NE-stimulated O2 consumption by fetal BAT cells occurred in offspring of mild diabetic pregnancies (807 +/- 60, P less than .001 v controls). A highly significant inverse correlation between serum glucose levels and maximal O2 consumption by fetal BAT was observed in fetuses from mild and severe diabetic pregnancies (r = -.98, P less than .005), and there was no correlation between these two parameters in offspring of normal pregnancies. A significant inverse correlation was observed between maximal O2 consumption by fetal BAT cells and serum insulin levels in offspring of both control and diabetic pregnancy (r = -.74; P less than .02). Tissue cytochrome oxidase activity was lower in offspring of severely affected diabetic does, indicating a reduction in BAT mitochondrial content compared with controls. BAT mitochondria from fetuses of severely diabetic does exhibited reduced 3H-GDP capacity, which was 2.5-fold lower than controls.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Oxygen consumption and guanosine diphosphate binding by fetal brown adipose tissue in diabetic pregnancy. 254 31

Regional variations in capillary density, glucose utilization rate, and activities of the glycolytic enzyme lactate dehydrogenase and the mitochondrial enzyme cytochrome oxidase were compared in the rat brain. The distributions of capillaries and enzymes were studied by means of histochemical staining techniques, and glucose metabolism was measured by means of [14C]2-deoxyglucose autoradiography. Analysis of 18 gray and five white matter regions revealed a positive correlation between capillary density and glucose utilization rate. A negative correlation was found between capillary density and lactate dehydrogenase among gray matter structures. Analysis of capillaries and enzymes was also performed within laminated histological fields: hippocampus, olfactory bulb, and olfactory cortex. In general, this revealed reciprocal patterns of staining for lactate dehydrogenase and cytochrome oxidase. Capillary density paralleled cytochrome oxidase activity. The zones of intense staining for lactate dehydrogenase and cytochrome oxidase corresponded to the synaptic terminal fields of different input pathways. These findings demonstrate distinct distributions of a glycolytic and an oxidative enzyme within the brain which are at least partly associated with pathway specificity.
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PMID:Metabolic anatomy of brain: a comparison of regional capillary density, glucose metabolism, and enzyme activities. 255 35

Hypoxic-ischaemic injury to the brain is an important cause of perinatal death and seems to be the commonest cause of permanent neurodevelopmental disability in newborn infants who survive after intensive care. If this type of brain injury is to be prevented and treatment put on a rational basis, non-invasive methods are required for defining its mechanisms. This review has considered two such methods: magnetic resonance spectroscopy and near infrared spectroscopy. Magnetic resonance spectroscopy is used to measure, in brain tissue, the concentrations of the 'high energy' phosphorus metabolites that are dependent for their synthesis on the processes of oxidative phosphorylation. Intracellular pH can also be measured. Normal maturational changes in the brain have been defined and abnormalities detected in a range of conditions where hypoxic-ischaemic injury was suspected to have occurred. In laboratory animals the acute effects of curtailment of oxygen supply to the brain ('primary' energy failure) have been observed, and the effects of two commonly used treatments, infusions of sodium bicarbonate and glucose, have been tested. After resuscitation of newborn infants from severe intrapartum asphyxia, a latent period has often been noted before energy failure became detectable. This 'secondary' energy failure is due to a variety of damaging reactions initiated by the acute hypoxicischaemic episode and reperfusion of the brain. It is possible that in the future irreversible injury to brain cells following the episode may be prevented or ameliorated by the prompt use of cerebroprotective agents. The extent of abnormalities detected by magnetic resonance spectroscopy has prognostic implications: evidence of severe energy failure in the first days of life was regularly associated with subsequent death or with severe neurodevelopmental impairments. Many technical developments in magnetic resonance spectroscopy are under way, particularly employing proton (1H) spectroscopy, which will allow the intracerebral concentrations of a wide range of metabolites, including neurotransmitters, to be measured. The combination of spectroscopy with magnetic resonance imaging will permit quantitative data to be obtained from selected volumes within the brain. Near infrared spectroscopy is used to make observations at the cotside of the intracerebral concentrations of the chromophores oxyhaemoglobin, deoxyhaemoglobin, and oxidised cytochrome aa3, and it therefore provides information complementary to that obtained by magnetic resonance spectroscopy. Measurements can also be made of cerebral blood flow, cerebral blood volume, and other haemodynamic indices; in addition, the rea
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PMID:Magnetic resonance and near infrared spectroscopy for investigation of perinatal hypoxic-ischaemic brain injury. 267 61

To study the functional organization of secondary visual cortex (V2) in the primate, 14C-2-deoxy-d-glucose (DG) was injected while macaque monkeys were shown specific visual stimuli. Wherever possible, patterns of DG uptake were compared with the position of dark and light cytochrome oxidase (cytox) stripes (Tootell et al., 1983). Often, the DG effects of 2 different stimuli were compared in the same hemisphere to eliminate ambiguities inherent in between-animal comparisons. Data were obtained from a large number of animals in conjunction with related DG studies in area V1 (primary visual or striate cortex). The following conclusions were reached: (1) in some macaque monkeys, dark cytox stripes were faint or absent. Although this could conceivably be due to poor staining technique, some evidence suggests that the lack of enzyme stripe pattern is real. In all animals, including those that showed poor or no cytox staining evidence for stripes, the functional architecture revealed by the DG was consistently present and robust. (2) Uniform gray stimuli produce a relatively uniform pattern and minimal stimulus-related DG uptake. (3) Eye movements per se produce some uptake in the V2 stripes. (4) Very generalized visual stimulation conditions (e.g., binocular stimulation with a grating of varied orientation and varied spatial frequency) produced a pattern of uptake that is greatest in both sets of dark cytox stripes and lighter in the light cytochrome stripes. (5) In both the DG and cytox results, the V2 "stripes" are more accurately described as stripe-shaped collections of patches. (6) In almost all cases, DG patterns were columnar in shape, extending from white matter to cortical surface. The boundaries of the columns were most sharply defined, and the contrast was highest, in layers 3B/4, becoming slightly more blurry and lower in contrast in other layers. Laminar differences between DG patterns in V2 were almost negligible, compared with the profound laminar differences in macaque V1. (7) There is no DG evidence for, and much against, the possibility of an ocular dominance architecture in V2. (8) There are orientation columns in macaque V2. DG-labeled orientation columns are spaced further apart than those in V1, by a factor of about 1.6, but the columns are not correspondingly wider. (9) Spatially diffuse variations in color produce high uptake confined, at least largely, to the thin cytox stripes. (10) There is evidence for spatially antagonistic color surrounds in color cells in the thin stripes.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Functional anatomy of the second visual area (V2) in the macaque. 276 60

The effect of hibernation and arousal on brown adipose tissue (BAT) cytochrome-c oxidase activity and GDP binding, as well-circulating metabolites, have been studied in the 13-lined ground squirrel. Control animals (warm adapted) were housed continuously at 23 degrees C, while the remaining animals were transferred into a cold room (4 degrees C) for 8 days to induce hibernation. Hibernating animals were killed while deeply hibernating. Aroused animals were manually stimulated to induce arousal or had spontaneously aroused on the day of the experiment. BAT weight as well as mitochondrial mass were increased in both groups of cold-adapted animals, relative to controls. A substantial increase in GDP binding, however, was seen only in aroused animals, an observation confirmed by Scatchard analysis. Arousal was also accompanied by marked alterations in the levels of several circulating metabolites. Plasma free fatty acids declined by approximately 20% despite a three- to fourfold increase in plasma glycerol concentrations. Plasma lactate levels increased eightfold, while concentrations of beta-hydroxybutyrate were five times lower during arousal than hibernation. These data are consistent with the idea that the oxidation of free fatty acids, glucose, and ketone bodies are all increased during arousal. In conclusion, we have found that cold adaptation and subsequent hibernation increases BAT thermogenic capacity in the 13-lined ground squirrel. However, this increase in thermogenic potential is not manifested as a substantial increase in BAT thermogenic activity until arousal is initiated.
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PMID:Brown fat GDP binding and circulating metabolites during hibernation and arousal. 278 56

A 42-year-old woman had a 10-year history of external ophthalmoplegia, malabsorption resulting in chronic malnutrition, muscle atrophy and polyneuropathy. Computer tomography revealed hypodensity of her cerebral white matter. A metabolic disturbance consisted of lactic acidosis after moderate glucose loads with increased excretion of hydroxybutyric and fumaric acids. Post-mortem studies revealed gastrointestinal scleroderma as the morphological manifestation of her malabsorption syndrome, ocular and skeletal myopathy with ragged red fibers, peripheral neuropathy, vascular abnormalities of meningeal and peripheral nerve vessels. Biochemical examination of the liver and muscle tissues revealed a partial defect of cytochrome-c-oxidase (complex IV of the respiratory chain). This mitochondrial multisystem disorder may represent a separate entity to be classified between the spectrum of myoencephalopathies and oculo-gastrointestinal muscular dystrophy.
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PMID:Myo-, neuro-, gastrointestinal encephalopathy (MNGIE syndrome) due to partial deficiency of cytochrome-c-oxidase. A new mitochondrial multisystem disorder. 282 22


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