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 new rapid procedure for the preparation of monodispersed highly active cytochrome-c oxidase from bovine heart is described. The crucial step is the separation of cytochrome-c oxidase from cytochrome-c reductase by selective solubilization in the non-ionic detergents Triton X-100 or lauryl beta-D-maltoside. The enzyme is purified by subsequent anion-exchange chromatography. The preparation is finished within two days yielding approximately 60% of the oxidase present in mitochondria. The enzyme has a heme alpha/protein ratio of 9.7 +/- 0.5 nmol/mg, approximately equal to the theoretical value of 9.77 nmol/mg based on a molecular mass of 204.696 kDa for the protein monomer. SDS/PAGE of the preparation reveals the presence of the well-known thirteen protein components. Quantitative Edman degradation of the enzyme exclusively releases the known ten N-terminal residues; three of the thirteen protein components are blocked at the N-terminus. The preparation is highly active with maximal turnover numbers of approximately 600 s-1, identical to the maximal activity found in the mitochondrial membrane under these conditions. No g = 12 signal and no adventitious copper signal are observed in the EPR spectrum. The enzyme exhibits a fast monophasic reaction with cyanide. Determination of the metal contents of the enzyme indicates the stoichiometric presence of three copper ions besides two iron, one magnesium and one zinc ion in relation to the 94 sulfur atoms of the protein monomer. Gel-filtration experiments show a monodispersed dimeric association to form a complex of approximately 500 kDa. The phosphorus content 44 +/- 6.8 atoms/dimer, results from 59% cardiolipin, 23% phosphatidylethanolamine and 18% phosphatidylcholine, indicating a stable lipid shell, different from other previously described preparations. Crystals have been obtained from these preparations and are investigated for their suitability for X-ray work.
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PMID:Integral cytochrome-c oxidase. Preparation and progress towards a three-dimensional crystallization. 785 42

Cleavage of amino-terminal octapeptides, F/L/IXXS/T/GXXXX, by mitochondrial intermediate peptidase (MIP) is typical of many mitochondrial precursor proteins imported to the matrix and the inner membrane. We previously described the molecular characterization of rat liver MIP (RMIP) and indicated a putative homolog in the sequence predicted from gene YCL57w of yeast chromosome III. A new yeast gene, MIP1, has now been isolated by screening a Saccharomyces cerevisiae genomic library with an RMIP cDNA probe. MIP1 predicts a protein of 772 amino acids (YMIP), which is 54% similar and 31% identical to RMIP and includes a putative 37-residue mitochondrial leader peptide. RMIP and YMIP contain the sequence LFHEMGHAM HSMLGRT, which includes a zinc-binding motif, HEXXH, while the predicted YCL57w protein contains a comparable sequence with a lower degree of homology. No obvious biochemical phenotype was observed in a chromosomally disrupted ycl57w mutant. In contrast, a mip1 mutant was unable to grow on nonfermentable substrates, while a mip1 ycl57w double disruption did not result in a more severe phenotype. The mip1 mutant exhibited defects of complexes III and IV of the respiratory chain, caused by failure to carry out the second MIP-catalyzed cleavage of the nuclear-encoded precursors for cytochrome oxidase subunit IV (CoxIV) and the iron-sulfur protein (Fe-S) of the bc1 complex to mature proteins. In vivo, intermediate-size CoxIV was accumulated in the mitochondrial matrix, while intermediate-size Fe-S was targeted to the inner membrane. Moreover, mip1 mitochondrial fractions failed to carry out maturation of the human ornithine transcarbamylase intermediate (iOTC), specifically cleaved by RMIP. A CEN plasmid-encoded YMIP protein restored normal MIP activity along with respiratory competence. Thus, YMIP is a functional homolog of RMIP and represents a new component of the yeast mitochondrial import machinery.
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PMID:MIP1, a new yeast gene homologous to the rat mitochondrial intermediate peptidase gene, is required for oxidative metabolism in Saccharomyces cerevisiae. 803 33

Brain tissue from normal individuals with incidental Lewy bodies and cell loss in pigmented substantia nigra neurons (asymptomatic Parkinson's disease) and age-matched control subjects without nigral Lewy bodies was examined biochemically. There was no difference in dopamine levels or dopamine turnover in the caudate and putamen of individuals with incidental Lewy body disease compared to control subjects. There were no differences in levels of iron, copper, manganese, or zinc in the substantia nigra or other brain regions from the individuals with incidental Lewy body disease compared to those from control subjects. Similarly, ferritin levels in the substantia nigra and other brain areas were unaltered. There was no difference in the activity of succinate cytochrome c reductase (complexes II and III) or cytochrome oxidase (complex IV) between incidental Lewy body subjects and control subjects. Rotenone-sensitive NADH coenzyme Q1 reductase activity (complex I) was reduced to levels intermediate between those in control subjects and those in patients with overt Parkinson's disease, but this change did not reach statistical significance. The levels of reduced glutathione in substantia nigra were reduced by 35% in patients with incidental Lewy body disease compared to control subjects. Reduced glutathione levels in other brain regions were unaffected and there were no changes in oxidized glutathione levels in any brain region. Altered iron metabolism is not detectable in the early stages of nigral dopamine cell degeneration. There may be some impairment of mitochondrial complex I activity in the substantia nigra in Parkinson's disease.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Indices of oxidative stress and mitochondrial function in individuals with incidental Lewy body disease. 828 90

The polarized X-ray absorption spectra of the copper, iron and zinc sites of mitochondrial cytochrome oxidase in oriented membrane multilayers have been examined. The copper X-ray absorption edge spectra indicate the presence of a tetragonal copper, which we assign as CuB, oriented with the long axis approximately orthogonal to the membrane normal. We have also detected the presence of a relatively long (2.6 A) Cu-S or Cu-Cl interaction, which we assign to a copper-thioether (probably Met210) coordination at the CuA site, with the bond oriented along the membrane normal. The coordination of the zinc, the iron and the CuB heme a3 binuclear site are discussed.
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PMID:X-ray absorption spectroscopy of oriented cytochrome oxidase. 838 38

There is considerable physiological evidence for the compartmentalization of mammalian visual cortex into functional columnar modules, representing features of visual information processing such as eye and orientation specificity. However, anatomical markers of visual cortical compartmentalization have been described only for primate visual cortex. In this report, we describe an interdigitated mosaic of four neuroactive molecules which demarcate two distinct columnar systems in the kitten visual cortex. Serotonin 1C receptors and synaptic zinc were found to demarcate columns within layer IV of kitten visual cortex, which were interdigitated with a second, patchy system characterized by increased levels of cytochrome oxidase and acetylcholinesterase. In primate visual cortex, as well as in the kitten, synaptic zinc was periodically distributed in a manner precisely complementary to cytochrome oxidase. These findings provide an anatomical framework on which unifying hypotheses of the functional organization of columnar systems in mammalian visual cortex can be built.
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PMID:An interdigitated columnar mosaic of cytochrome oxidase, zinc, and neurotransmitter-related molecules in cat and monkey visual cortex. 841 54

Inactivation of YME1 in yeast causes several distinct phenotypes: an increased rate of DNA escape from mitochondria, temperature-sensitive growth on nonfermentable carbon sources, extremely slow growth when mitochondrial DNA is completely absent from the cell, and altered morphology of the mitochondrial compartment. The protein encoded by YME1, Yme1p, contains two highly conserved sequence elements, one implicated in the binding and hydrolysis of ATP, and the second characteristic of active site residues found in neutral, zinc-dependent proteases. Both the putative ATPase and zinc-dependent protease elements are necessary for the function of Yme1p as genes having mutations in critical residues of either of these motifs are unable to suppress any of the phenotypes exhibited by yme1 deletion strains. Yme1p co-fractionates with proteins associated with the mitochondrial inner membrane, is tightly associated with this membrane, and is oriented with the bulk of the protein facing the matrix. Unassembled subunit II of cytochrome oxidase is stabilized in yme1 yeast strains. The data support a model in which Yme1p is an ATP and zinc-dependent protease associated with the matrix side of the inner mitochondrial membrane. Subunit II of cytochrome oxidase, when not assembled into a higher order complex, is a likely substrate of Yme1p.
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PMID:Biochemical and functional analysis of the YME1 gene product, an ATP and zinc-dependent mitochondrial protease from S. cerevisiae. 868 60

We describe the purification of a H2O-producing NADH oxidase from the protozoan parasite Giardia duodenalis. The enzyme is a monomeric flavoprotein containing flavin adenine dinucleotide in a 1:1 molar ratio with the polypeptide. The NADH oxidase has an apparent molecular mass of 46 kDa and was homogenous as determined by denaturing gel electrophoresis and N-terminal amino acid sequencing. NADPH could substitute for NADH as an electron donor with a K(m) value of 4.2 microM for NADH and 16 microM for NADPH (pH 7.8 at room temperature). With oxygen as the primary electron acceptor under aerobic conditions, the pure enzyme did not produce O.-2 nor H2O2 as stoichiometric products of oxygen reduction, implicating H2O as the end product and obviating the need for superoxide dismutase. The ability to utilise oxygen explains the apparent respiration of the amitochondrial fermentative metabolism of Giardia. Mercurials, flavoantagonists and heavy metals (Cu2+ and Zn2+) inhibited this activity. Under anaerobic conditions the enzyme catalysed electron transfer at lower efficiencies to other electron acceptors including nitroblue tetrazolium, potassium ferricyanide, FAD and FMN, using either NADH or NADPH as electron donors. NADPH, however, was a more efficient electron donor. Cytochrome c was not reduced under any assay conditions used. The enzyme reduced the nitrofuran drugs, furazolidone (an antigiardial) and nitrofurantoin, to their toxic radical forms as determined by EPR. Metronidazole, a nitroimidazole, was not reduced. Pure NADH oxidase did not demonstrate ferredoxin:NAD(P)1 oxidoreductase activity since it could not accept electrons from reduced ferredoxin to regenerate NAD(P)H. The G. duodenalis NADH oxidase may, therefore, function as a terminal oxidase, similar to the mitochondrial cytochrome oxidase, and in the maintenance of an optimum intracellular redox ratio. This report of a flavoenzyme from Giardia places Giardia close to the anaerobic bacteria in evolutionary terms.
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PMID:A H2O-producing NADH oxidase from the protozoan parasite Giardia duodenalis. 889 1

Using immunocytochemistry we have analyzed 8 pituitary oncocytomas, 14 null cell adenomas, and 2 oncocytomas of the parotid gland (Warthin's tumor). The proportions of adenoma cells that are positive for mitochondrial protein (MP), cytochrome oxidase (COX), and manganese-superoxide dismutase (Mn-SOD) were significantly higher in pituitary oncocytomas than in null cell adenomas (MP P < 0.001, COX P < 0.001, Mn-SOD P < 0.05). In pituitary oncocytomas, MP-positive cells were distributed unevenly but in clusters or in islets admixed with some MP-negative cells, and corresponded to COX-positive cells. In contrast, almost all of the oxyphilic epithelial cells of Warthin's tumor were positive for MP, COX, and Mn-SOD. On the other hand, both pituitary tumors displayed similar findings with regard to the proportion of adenoma cells immunoreactive for copper/zinc-SOD and adenohypophysial hormones, the Ki-67 (MIB-1) proliferating cell index, and the mean number of argyrophilic nucleolar organizer regions. It was confirmed that immunocytochemical identification of MP and COX is useful for distinguishing pituitary oncocytomas from null cell adenomas. Although it remains to be determined whether oncocytomas originate from oncocytic changes of tumor cells or from neoplastic transformation of oncocytic cells, it appears that tumorigenesis of pituitary oncocytomas differs from that of Warthin's tumor.
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PMID:Immunocytochemical study of pituitary oncocytic adenomas. 922 29

When hepatocytes are incubated with the chelator diamsar, two pools can be identified, which we have termed extractable and nonextractable. On entering the hepatocyte, 67Cu first associates with the extractable pool and, after approximately 2 h, moves to the nonextractable pool. Both pools demonstrate saturation and are filled as a function of Cu concentration and incubation time. Using the Michaelis-Menten equation, we have estimated the size of the pools after incubation with 67Cu for 30 min and 4 h. During this period the extractable pool decreases in size from 200 +/- 27 to 116 +/- 5 pmol/microgram DNA, whereas the nonextractable pool increases from 28 +/- 9 to 77 +/- 11 pmol/microgram DNA. Movement of Cu from the nonextractable pool to the extractable pool is slow and incomplete. Using [3H]diamsar, we demonstrate that uptake of the chelator is not rate limiting and probably does not occur by pinocytosis. Incubation with diamsar does not affect the activity of superoxide dismutase or cytochrome-c oxidase, although it does prevent the incorporation of 67Cu into ceruloplasmin. Incubation with zinc, which induces metallothionein, results in an increase in 67Cu associated with the nonextractable pool, suggesting that 67Cu-metallothionein constitutes at least part of the nonextractable pool.
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PMID:Characterization of intracellular copper pools in rat hepatocytes using the chelator diamsar. 922 75

Male Holtzman rats were offered a semipurified low-copper (Cu) diet (0.36 mg Cu/kg) for 5-6 weeks to further characterize cardiac hypertrophy, which accompanies Cu deficiency. Cu-adequate (controls) were given supplemental Cu (20 micrograms/ml) in their drinking water, and Cu-deficient rats were given deionized water. Cu-deficient rats had lower plasma ceruloplasmin activity, lower hemoglobin levels, higher heart weights, and similar body weights compared with Cu-adequate rats. The relative degree of hypertrophy in the right ventricle of Cu-deficient rats was significantly higher (2.3-fold) than that in the left ventricle and atria (both were 1.9-fold higher than the values in Cu-adequate rats). Edema was not detected. Ventricles and atria of Cu-deficient rats had markedly lower Cu and no significant differences in iron concentrations compared with Cu-adequate rats. Heart protein concentrations were not altered consistently by Cu deficiency. Enzyme activities of the cuproenzymes cytochrome-c oxidase (CCO), copper, zinc-superoxide dismutase (SOD), dopamine beta-monooxygenase (DBM), peptidylglycine alpha-amidating monooxygenase (PAM), and the selenoenzyme glutathione peroxidase (GPX) were measured in the atria and ventricles. Cu deficiency resulted in lower specific activities of all cuproenzymes, with the exception of ventricular PAM. GPX was not altered by chamber region or diet. Specific activity of PAM was 200-fold higher in atria than in ventricles in control rats. Catecholamine analyses by HPLC confirmed that, like ventricular tissue, atria of Cu-deficient rats had lower noreplnephrine and higher dopamine concentrations, consistent with lower DBM activity. Another experiment detected no differences between the two dietary groups in mean arterial blood pressure, heart rates, or responses after challenge with anglotensin II, phenylepherine, or acetylocholine in cannulated rats. In this Cu-deficient rat model, all chambers of the heart exhibit similar and marked hypertrophy. Biochemical alterations following dietary Cu deficiency were also similar in atria and ventricles. The hypertrophic response appears different from the response to simple pressure or volume overload.
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PMID:Atria and ventricles of copper-deficient rats exhibit similar hypertrophy and similar altered biochemical characteristics. 927 Jul 21


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