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)

Malonyl-CoA decarboxylase (EC 4.1.1.9) was purified 500--600-fold from the mammary gland extracts by (NH4)2SO4 precipitation, gel filtration with Sepharose 4B, anion-exchange chromatography with QAE-Sephadex, and chromatography with NADP-Agarose. This enzyme (spec. act. 200--300 nmol/min per mg protein) had a molecular weight of approx. 170 000. It did not cross-react with rabbit antiserum prepared against either fatty acid synthetase from the mammary gland or malonyl-CoA decarboxylase from the uropygial gland of goose. The decarboxylase showed a pH optimum near 8.5--9.0 and a Km of 0.33 mM, decarboxylated neither malonic acid nor methylmalonyl-CoA and was inhibited by thiol directed reagents but not by avidin. Sucrose density gradient centrifugation of the gland homogenate showed that the major peak of decarboxylase activity coincided with that of cytochrome oxidase. Breakage of mitochondria released greater than 80% of the decarboxylase activity into the 105,000 X g supernatant, suggesting that malonyl-CoA decarboxylase may be located in the mitochondrial matrix.
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PMID:Malonyl-CoA decarboxylase from the mammary gland of lactating rat. Purification, properties and subcellular localization. 71 70

Adult rats received chronic dialytic delivery devices that exposed the striatum to a 100 mM, 400 mM, or 4 M solution of the reversible succinate dehydrogenase inhibitor malonic acid (MA). Three weeks of exposure to 100 or 400 mM MA produced no significant reduction in striatal cytochrome oxidase staining, whereas striata chronically exposed to 1 and 4 M MA showed a significant and dose-related reduction in cytochrome oxidase staining. In striata exposed to 1 M MA, analysis of regions radial to the necrotic core revealed significant reduction of nissl cell staining with relative sparing of NADPH-diaphorase-containing neurons. Although 100 and 400 mM MA failed to produce lesions, both of these concentrations significantly decreased the number of striatal calbindin (CALB) immunoreactive perikarya. The reduction in CALB immunoreactivity was partly reversed in animals allowed to survive 4 weeks after cessation of exposure to 400 mM MA. These results indicate that, like striatal lesions produced by quinolinic acid, lesions produced by chronic exposure to MA possess a Huntington's disease-like pattern of selective neurodegeneration. In addition, exposure to subthreshold MA concentrations (100 and 400 mM) produce widespread transient changes in striatal CALB that may be associated with a premorbid state of neuronal dysfunction.
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PMID:Chronic administration of malonic acid produces selective neural degeneration and transient changes in calbindin immunoreactivity in rat striatum. 755 44

Excitotoxicity and defects in neuronal energy metabolism have both been implicated in the pathogenesis of neurodegenerative disease. These two mechanisms may be linked through the NMDA receptor, activation of which is dependent on neuronal membrane potential. Because the ability to maintain membrane potential is dependent on neuronal energy metabolism, bioenergetic defects may affect NMDA receptor-mediated excitotoxicity. We now report that reversible inhibition of succinate dehydrogenase (SDH), an enzyme central to both the tricarboxylic acid cycle and the electron transport chain, produces an "excitotoxic" lesion in rat striatum that can be blocked by the NMDA antagonist MK-801. Male Sprague-Dawley rats received intrastriatal stereotaxic injections of the SDH inhibitor malonic acid (1 or 2 mumol) in combination with intraperitoneal injections of vehicle or MK-801 (5 mg/kg) 30 min before and 210 min after malonic acid. Animals were killed 72 h after surgery, and brains were processed for histology, cytochrome oxidase activity, and [3H]MK-801 and [3H]AMPA autoradiography. The higher dose of malonic acid (2 mumol) produced large lesions that were markedly attenuated by treatment with MK-801 (28.1 +/- 3.6 vs. 4.7 +/- 2.6 mm3; p < 0.001). [3H]MK-801 and [3H]AMPA binding were reduced in the lesions by 60 and 63%, respectively. One micromole of malonic acid produced smaller lesions that were almost completely blocked by MK-801 treatment (9.6 +/- 1.3 vs. 0.06 +/- 0.04 mm3; p < 0.0001). The toxic effects of malonic acid were due specifically to inhibition of SDH inasmuch as coinjection of a threefold excess of succinate with the malonic acid blocked the striatal lesions (p < 0.002).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Inhibition of succinate dehydrogenase by malonic acid produces an "excitotoxic" lesion in rat striatum. 836 Jun 80

Malonate is an inhibitor of cellular metabolism, which, following intrastriatal injection, induces a striatal pathology similar to that seen in Huntington's disease. In two parallel studies, we have investigated the suggested relationship between the neuronal vulnerability to metabolic toxicity and the decline in metabolic function with increasing age. The first experiment investigated malonate-induced neuronal loss in animals aged from 6 weeks up to 27 months, and the second assessed the activities of two mitochondrial enzymes, succinate dehydrogenase and cytochrome oxidase (CYTOX) in animals aged 6 weeks, 3, 8 and 18 months. In the first study, male Lister-Hooded rats received intrastriatal stereotaxic injections of malonate (0.5 or 1.0 M). Animals were killed 10 days after surgery, and the brains were stained with cresyl violet and processed for NADPH-diaphorase activity and glial fibrillary-acidic-protein (GFAP) immunohistochemistry. Animals aged 6 months and older exhibited over 60% striatal neuronal loss. However, the degree of neuronal loss did not show any age-related increase in rats between 6 and 27 months of age, indicating that the extent of malonate-induced toxicity does not increase with age in animals older than 6 months. Infusion of 0.5 M malonate produced smaller lesions, which also demonstrated a consistent extent of neuronal loss from 6 months onwards. Metabolic enzyme activities were decreased in the striatum with increasing age, although this effect was only significant for CYTOX activity. Thus, the pattern of malonate-induced neuronal loss in aged animals partially reflects the changes in metabolic activity during ageing.
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PMID:Age-dependence of malonate-induced striatal toxicity. 1104 58

The mode of action of the anti-fungal compounds, 1,10-phenanthroline (phen), [Cu(phen)2(mal)] x 2H2O, [Mn(phen)2(mal)] x 2H2O and [Ag2(phen)3(mal)] x 2H2O (malH2 = malonic acid), was examined using the pathogenic yeast Candida albicans. The compounds have minimum inhibitory concentrations (MIC's) in the range 1.25-5.0 microg cm(-3) and at a concentration of 10 microg cm(-3) display some fungicidal activity. Yeast cells exposed to these drugs show a diminished ability to reduce 2,3,5-triphenyltetrazolium chloride (TTC), indicating a reduction in respiratory function. Treating exponential and stationary phase yeast cells with phen and the Cu(II) and Mn(II) complexes causes a dramatic increase in oxygen consumption. All of the drugs promote reductions in the levels of cytochromes b and c in the cells, whilst the Ag(I) complex also lowers the amount of cytochrome aa3. Cells treated with phen and the Cu(II) and Ag(I) species show reduced levels of ergosterol whilst the Mn(II) complex induces an increase in the sterol concentration. The general conclusion is that the drugs damage mitochondrial function and uncouple respiration. That the drugs are not uniformly active suggests their bioactivity has a degree of metal-ion dependency. Phen and metal-phen complexes represent a novel set of highly active anti-fungal agents whose mode of action is significantly different to that of the polyene and azole prescription drugs.
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PMID:Mode of anti-fungal activity of 1,10-phenanthroline and its Cu(II), Mn(II) and Ag(I) complexes. 1257 90

The anaphylactic release of histamine from perfused, chopped guinea pig lung is very sensitive to changes in the NaCl concentration of the containing medium, and it is ionic strength rather than particle concentration which is critical. Consequently, in studies with inhibitors care must be taken to avoid inadvertently increasing ionic strength and thereby misinterpreting the cause of the inhibition. Since immune hemolysis exhibits a similar sensitivity to changes in the NaCl concentration of the suspending medium, salicylaldoxime and phlorizin, which prevent the participation of the third component of complement in immune hemolysis, were investigated for their effect on the anaphylactic reaction. Salicylaldoxime is a potent inhibitor of in vitro anaphylaxis in guinea pig lung, but phlorizin is only a weak inhibitor. Potassium cyanide, 1 mM, inhibits the anaphylactic release of histamine most effectively if the duration of contact between the tissue and the cyanide prior to antigen addition is minimal; preincubation of the tissue with cyanide prior to antigen addition results in progressive diminution of inhibition even when there is only minimal loss of cyanide from the containing medium. The anaphylactic release of histamine from perfused whole lungs or suspensions of blood-free chopped lung is not prevented by the cytochrome oxidase inhibitor, carbon monoxide. In addition, 2-heptyl 4 hydroxyquinoline N oxide and malonic acid, which inhibit aerobic metabolism at different sites, do not prevent the reaction. These studies and those with cyanide indicate that the anaphylactic release of histamine in guinea pig lung is not dependent on cytochrome-mediated aerobic metabolism.
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PMID:Anaphylaxis in chopped guinea pig lung. III. Effect of carbon monoxide, cyanide, salicylaldoxime, and ionic strength. 1368 96

Chlorella vulgaris Beyerinck (Emerson's strain), fails to grow in the dark even when sugars are provided. This phenomenon was clearly demonstrated in the alga, C. vulgaris, for which the growth rate in darkness on a glucose medium remained constant for 2 days and then declined to approach zero. Pigment concentrations also declined in darkness. Changes in flow rate of 1% CO(2)-in-air from zero to 7 ml per minute caused a progressive increase in the dark growth rate over a 5-day period, but did not maintain growth in the dark. Rates above 7 ml per minute produced no changes in growth rates.White light intensities below the compensation point of the alga maintained heterotrophic growth. The saturation value for this response was 0.8 muw/cm(2). White light also initiated growth in nongrowing cultures transferred from darkness to light.The action spectrum for heterotrophic growth indicated a porphyrin as the active pigment. Light in the 425 mmu region was 4 times as effective as white light in stimulating heterotrophic growth. A secondary peak of growth stimulation occurred in the 575 mmu region.The respiration of glucose by the alga was stimulated by low intensities of white light. This response was not immediate, but was clearly present after the third day of incubation.Malonate and cyanide were inhibitory to growth of C. vulgaris on inorganic medium or glucose medium under 300 ft-c of white light. These data suggested that succinic dehydrogenase and cytochrome oxidase systems were present.Substances inhibitory to growth were excreted into the medium under dark-growth conditions, and 2 of these substances were indentified as formic and acetic acids.The evidence suggested that respiration of glucose cannot proceed for an extended period of time in darkness. The reason for this is postulated to be the lack of a cytochrome or a cytochrome precursor.
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PMID:Responses of Heterotrophic Cultures of Chlorella vulgaris Beyerinck to Darkness and Light. II. Action Spectrum for and Mechanism of the Light Requirement for Heterotrophic Growth. 1665 34

The ability of the synthesized compounds of germanium with bioligands to affect the biosynthesis and activity of alpha-amylase and alpha-L-rhamnosidase has been studied. It was established the most complexes tested induced biosyntheis of alpha-amylase of Bacillus subtilis 147 (119-252%) with the exception of Pam (Pyracetam) and II (Ge-nicotinic-citric acid). At the same time the biosynthesis of alpha-amylase of Bacillus licheniformis 234 and alpha-L-rhamnosidase of Penicillium commune was inhibited by a number of synthesized compounds. The complexes IV (Ge-malonic acid) and VIII (Ge-nicotinamide-malonic acid) did not exert any effect on the biosynthesis of alpha-amylase however complex IV stimulated alpha-L-rhamnosidase biosynthesis on the 3rd day of producer cultivation. The study of influence of the studied germanium compounds on the activity of alpha-amylase and alpha-L-rhamnosidase gives every reason to suppose that they are the inhibitors of the above-mentioned enzymes.
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PMID:[The influence of coordinational germanium compounds on the activity of glycosidases]. 1768 26

Hyoscyamus albus hairy roots secrete riboflavin under Fe-deficient conditions. To determine whether this secretion was linked to an enhancement of respiration, both riboflavin secretion and the reduction of 2,3,5-triphenyltetrazolium chloride (TTC), as a measure of respiration activity, were determined in hairy roots cultured under Fe-deficient and Fe-replete conditions, with or without aeration. Appreciable TTC-reducing activity was detected at the root tips, at the bases of lateral roots and in internal tissues, notably the vascular system. TTC-reducing activity increased under Fe deficiency and this increase occurred in concert with riboflavin secretion and was more apparent under aeration. Riboflavin secretion was not apparent under Fe-replete conditions. In order to examine which elements of the mitochondrial electron transport chain might be involved, the effects of the respiratory inhibitors, barbiturate, dicoumarol, malonic acid, antimycin, KCN and salicylhydroxamic acid (SHAM) were investigated. Under Fe-deficient conditions, malonic acid affected neither root growth, TTC-reducing activity nor riboflavin secretion, whereas barbiturate and SHAM inhibited only root growth and TTC-reducing activity, respectively, and the other compounds variously inhibited growth and TTC-reducing activity. Riboflavin secretion was decreased, in concert with TTC-reducing activity, by dicoumarol, antimycin and KCN, but not by SHAM. In Fe-replete roots, all inhibitors which reduced riboflavin secretion in Fe-deficient roots showed somewhat different effects: notably, antimycin and KCN did not significantly inhibit TTC-reducing activity and the inhibition by dicoumarol was much weaker in Fe-replete roots. Combined treatment with KCN and SHAM also revealed that Fe-deficient and Fe-replete roots reduced TTC in different ways. A decrease in the Fe content of mitochondria in Fe-deficient roots was confirmed. Overall, the results suggest that, under conditions of Fe deficiency in H. albus hairy roots, the alternative NAD(P)H dehydrogenases, complex III and complex IV, but not the alternative oxidase, are actively involved both in respiration and in riboflavin secretion.
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PMID:Iron deficiency induces changes in riboflavin secretion and the mitochondrial electron transport chain in hairy roots of Hyoscyamus albus. 2018 8

trans-Glutaconic acid (tGA) is an unsaturated C5-dicarboxylic acid which may be found accumulated in glutaric aciduria type I, whose pathophysiology is still uncertain. In the present work it was investigated the in vitro effect of increasing tGA concentrations on neurochemical and oxidative stress parameters in rat cerebral cortex. We observed that Na(+), K(+)-ATPase activity was reduced by tGA, but not creatine kinase, respiratory chain complex IV, and ATP synthase activities. On the other hand, tGA significantly increased lipid peroxidation (thiobarbituric acid-reactive species levels and spontaneous chemiluminescence), as well as protein oxidative damage (oxidation of sulfhydryl groups). tGA also significantly decreased nonenzymatic antioxidant defenses (TRAP and reduced glutathione levels). Our data suggest that tGA may be neurotoxic in rat brain.
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PMID:Neurotoxic effects of trans-glutaconic acid in rats. 2360 26


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