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Abstract: A subtractive hybridization and differential screening procedure was used to detect up-regulation of cytochrome c oxidase (CO) subunits I, III, and IV mRNA in the nucleus accumbens (NAc) of rats chronically treated with cocaine. Northern blot analyses of mRNA isolated from individual rats confirmed that CO subunit I was up-regulated by chronic, but not acute, cocaine in two brain regions, the NAc (33%) and caudate-putamen (CP)(35%). CO activity, used as a measure of metabolic activity, was increased by 88% in the NAc, and decreased by 20% in the medial prefrontal cortex (mPFC), the day after chronic treatment was terminated. CO enzyme activity was not regulated in the CP, or in other brain regions not involved in drug reward. CO activity in both the NAc and mPFC showed unique time-dependent patterns of regulation during the week after chronic cocaine treatment. 相似文献
3.
Jeffrey J. Regan Benjamin E. Ramirez Jay R. Winkler Harry B. Gray Bo G. Malmström 《Journal of bioenergetics and biomembranes》1998,30(1):35-39
Warburg showed in 1929 that the photochemical action spectrum for CO dissociation from cytochrome c oxidase is that of a heme protein. Keilin had shown that cytochrome a does not react with oxygen, so he did not accept Warburg's view until 1939, when he discovered cytochrome a
3. The dinuclear cytochrome a
3-CuB unit was found by EPR in 1967, whereas the dinuclear nature of the CuA site was not universally accepted until oxidase crystal structures were published in 1995. There are negative redox interactions between cytochrome a and the other redox sites in the oxidase, so that the reduction potential of a particular site depends on the redox states of the other sites. Calculated electron-tunneling pathways for internal electron transfer in the oxidase indicate that the coupling-limited rates are 9×105 (Cu A a) and 7×106 s–1 (a a
3); these calculations are in reasonable agreement with experimental rates, after corrections are made for driving force and reorganization energy. The best CuA-a pathway starts from the ligand His204 and not from the bridging sulfur of Cys196, and an efficient a-a
3 path involves the heme ligands His378 and His376 as well as the intervening Phe377 residue. All direct paths from CuA to a
3 are poor, indicating that direct CuA a
3 electron transfer is much slower than the CuA a reaction. The pathways model suggests a means for gating the electron flow in redox-linked proton pumps. 相似文献
4.
Paula Clemente Susana Peralta Alberto Cruz-Bermudez Lucía Echevarría Flavia Fontanesi Antoni Barrientos Miguel A. Fernandez-Moreno Rafael Garesse 《The Journal of biological chemistry》2013,288(12):8321-8331
Cytochrome c oxidase (COX) or complex IV of the mitochondrial respiratory chain plays a fundamental role in energy production of aerobic cells. In humans, COX deficiency is the most frequent cause of mitochondrial encephalomyopathies. Human COX is composed of 13 subunits of dual genetic origin, whose assembly requires an increasing number of nuclear-encoded accessory proteins known as assembly factors. Here, we have identified and characterized human CCDC56, an 11.7-kDa mitochondrial transmembrane protein, as a new factor essential for COX biogenesis. CCDC56 shares sequence similarity with the yeast COX assembly factor Coa3 and was termed hCOA3. hCOA3-silenced cells display a severe COX functional alteration owing to a decreased stability of newly synthesized COX1 and an impairment in the holoenzyme assembly process. We show that hCOA3 physically interacts with both the mitochondrial translation machinery and COX structural subunits. We conclude that hCOA3 stabilizes COX1 co-translationally and promotes its assembly with COX partner subunits. Finally, our results identify hCOA3 as a new candidate when screening for genes responsible for mitochondrial diseases associated with COX deficiency. 相似文献
5.
Cortical Cytochrome Oxidase Activity Is Reduced in Alzheimer's Disease 总被引:16,自引:5,他引:16
Abstract: A defect in energy metabolism may play a role in the pathogenesis of neurodegenerative diseases, such as Alzheimer's disease. In the present study, we examined the activities of the enzymes that catalyze oxidative phosphorylation in frontal, temporal, parietal, and occipital cortex from Alzheimer's disease patients and age-matched controls. Complex I and complex II–III activities showed a small decrease in occipital cortex, but were unaffected in the other cortical areas. The most consistent change was a significant decrease of cytochrome oxidase (complex IV) activity of 25–30% in the four cortical regions examined. These results provide further evidence of a cytochrome oxidase defect in Alzheimer's disease postmortem brain tissue. A deficiency in this key energy-metabolizing enzyme could lead to a reduction in energy stores and thereby contribute to the neurodegenerative process. 相似文献
6.
The strength and pattern of coevolution between amino acid residues vary depending on their structural and functional environment.
This context dependence, along with differences in analytical technique, is responsible for the different results among coevolutionary
analyses of different proteins. It is thus important to perform detailed study of individual proteins to gain better insight
into how context dependence can affect coevolutionary patterns even within individual proteins, and to unravel the details
of context dependence with respect to structure and function. Here we extend our previous study by presenting further analysis
of residue coevolution in cytochrome c oxidase subunit I sequences from 231 vertebrates using a statistically robust phylogeny-based maximum likelihood ratio method.
As in previous studies, a strong overall coevolutionary signal was detected, and coevolution within structural regions was
significantly related to the Cα distances between residues. While the strong selection for adjacent residues among predicted coevolving pairs in the surface
region indicates that the statistical method is highly selective for biologically relevant interactions, the coevolutionary
signal was strongest in the transmembrane region, although the distances between coevolving residues were greater. This indicates
that coevolution may act to maintain more global structural and functional constraints in the transmembrane region. In the
transmembrane region, sites that coevolved according to polarity and hydrophobicity rather than volume had a greater tendency
to colocalize with just one of the predicted proton channels (channel H). Thus, the details of coevolution in cytochrome c oxidase subunit I depend greatly on domain structure and residue physicochemical characteristics, but proximity to function
appears to play a critical role. We hypothesize that coevolution is indicative of a more important functional role for this
channel.
Electronic Supplementary Material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
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8.
Cytochrome c oxidase in prokaryotes 总被引:2,自引:0,他引:2
Bernd Ludwig 《FEMS microbiology letters》1987,46(1):41-56
Abstract Several heme aa 3 -type cytochrome c oxidases, purified from the cytoplasmic membranes of bacteria, are able to catalyze the same reactions as the structurally far more complex eukaryotic enzyme, i.e., electron transport from cytochrome c to oxygen coupled to proton translocation. However, these oxidases show a very simple subunit pattern, and moreover, individual polypeptides even have homologous amino-acid sequences. This review summarizes the present data on purified bacterial cytochrome c oxidases and relates these findings to results obtained with the mitochondrial enzymes. 相似文献
9.
Anna Atlante Sabatina Gagliardi Ersilia Marra Pietro Calissano Salvatore Passarella 《Journal of neurochemistry》1999,73(1):237-246
To gain some insight into the mechanism by which glutamate neurotoxicity takes place in cerebellar granule cells, two steps of glucose oxidation were investigated: the electron flow via respiratory chain from certain substrates to oxygen and the transfer of extramitochondrial reducing equivalents via the mitochondrial shuttles. However, cytochrome c release from intact mitochondria was found to occur in glutamate-treated cells as detected photometrically in the supernatant of the cell homogenate suspension. As a result of cytochrome c release, an increase of the oxidation of externally added NADH was found, probably occurring via the NADH-b5 oxidoreductase of the outer mitochondrial membrane. When the two mitochondrial shuttles glycerol 3-phosphate/dihydroxyacetone phosphate and malate/oxaloacetate, devoted to oxidizing externally added NADH, were reconstructed, both were found to be impaired under glutamate neurotoxicity. Consistent early activation in two NADH oxidizing mechanisms, i.e., lactate production and plasma membrane NADH oxidoreductase activity, was found in glutamate-treated cells. In spite of this, the increase in the cell NADH fluorescence was found to be time-dependent, an index of the progressive damage of the cell. 相似文献
10.
We present an analysis of the evolutionary rates of the cytochrome c oxidase subunit I genes of primates and other mammals. Five primate genes were sequenced, and this information was combined
with published data from other species. The sequences from simian primates show approximately twofold increases in their nonsynonymous
substitution rate compared to those from other primates and other mammals. The species range and the overall magnitude of
this rate increase are similar to those previously identified for the cytochrome c oxidase subunit II and cytochrome b genes.
Received: 22 July 1999 / Accepted: 21 February 2000 相似文献
11.
Ogunjimi EO Pokalsky CN Shroyer LA Prochaska LJ 《Journal of bioenergetics and biomembranes》2000,32(6):617-626
The role of subunit III in the function of mitochondrial cytochrome c oxidase is not clearly understood. Previous work has shown that chemical modification of subunit III with N,N-dicyclohexylcarbodiimide (DCCD) reduced the proton-pumping efficiency of the enzyme by an unknown mechanism. In the current work, we have employed biochemical approaches to determine if a conformational change is occurring within subunit III after DCCD modification. Control and DCCD modified beef heart enzyme were subjected to limited proteolysis in nondenaturing detergent solution. Subunit III in DCCD treated enzyme was more susceptible to chymotrypsin digestion than subunit III in the control enzyme. We also labeled control and DCCD-modified enzyme with iodoacetyl—biotin, a sulfhydryl reagent, and found that subunit III of the DCCD-modified enzyme was more reactive when compared to subunit III of the control enzyme, indicating an increase in reactivity of subunit III upon DCCD binding. The cross linking of subunit III of the enzyme induced by the heterobifunctional reagent, N-succinimidyl(4-azidophenyl -1,3-dithio)-propionate (SADP), was inhibited by DCCD modification, suggesting that DCCD binding prevents the intersubunit cross linking of subunit III. Our results suggest that DCCD modification of subunit III causes a conformational change, which most likely disrupts critical hydrogen bonds within the subunit and also those at the interface between subunits III and I in the enzyme. The conformational change induced in subunit III by covalent DCCD binding is the most likely mechanism for the previously observed inhibition of proton-pumping activity. 相似文献
12.
The effects of alloxan-diabetes and subsequent treatment with insulin on temperature kinetics properties of cytochrome oxidase
activity from rat brain mitochondria were examined. The enzyme activity decreased only at the late stage of diabetes which
was not normalized by insulin treatment; however at early stage of diabetes hyper-stimulation occurred. In the control animals
the Arrhenius plot was chair shaped with three energies of (E1, E2 and E3) and two phase transition temperatures (Tt1 and Tt2). At early diabetic stage the Arrhenius plot became biphasic and E1 and E2 decreased; insulin treatment reversed chair-shaped pattern with increase in E2. These changes correlated with transient changes in the phospholipids profiles especially decreased acidic phospholipids.
The temperature kinetics parameters were minimally affected at the late stage of diabetes or by insulin treatment. Thus at
the late stage the brain tissue seems to have readjusted to its insulin homeostasis. 相似文献
13.
用胆酸盐透析法将猪心线粒体细胞色素C氧化酶重组在含心磷脂和二肉豆寇磷脂酰胆碱的脂质体上,以还原态细胞色素C作为酶反应底物,记录脂酶体囊泡外介质液pH的变化,pH下降幅度可以反映细胞色素C氧化酶质子泵的功能。 心磷脂含量不同的细胞色素C氧化酶脂酶体质子泵功能不同。心磷脂含量在10%—40%(w/w)范围内,随心磷脂含量增高,该酶质子泵功能增强;当心磷艏含量超过50%时,该酶质子泵功能却随心磷脂含量的增加表现出下降的趋势。阿霉素可以与心磷脂紧密结合,抑制细胞色素C氧化酶的质子泵功能。然而,少量阿霉素却能增强含70%心磷脂的脂酶体的质子泵功能。 相似文献
14.
The superfamily of quinol and cytochrome c terminal oxidase complexes is related by a homologous subunit containing six positionally conserved histidines that ligate
a low-spin heme and a heme–copper dioxygen activating and reduction center. On the basis of the structural similarities of
these enzymes, it has been postulated that all members of this superfamily catalyze proton translocation by similar mechanisms
and that the CuA center found in most cytochrome c oxidase complexes serves merely as an electron conduit shuttling electrons from ferrocytochrome c into the hydrophobic core of the enzyme. The recent characterization of cytochrome c oxidase complexes and structurally similar cytochrome c:nitric oxide oxidoreductase complexes without CuA centers has strengthened this view. However, recent experimental evidence has shown that there are two ubiquinone(ol) binding
sites on the Escherichia coli cytochrome bo
3
complex in dynamic equilibrium with the ubiquinone(ol) pool, thereby strengthening the argument for a Q(H2)-loop mechanism of proton translocation [Musser SM et al. (1997) Biochemistry 36:894–902]. In addition, a number of reports
suggest that a Q(H2)-loop or another alternate proton translocation mechanism distinct from the mitochondrial aa
3
-type proton pump functions in Sulfolobus acidocaldarius terminal oxidase complexes. The possibility that a primitive quinol oxidase complex evolved to yield two separate complexes,
the cytochrome bc
1
and cytochrome c oxidase complexes, is explored here. This idea is the basis for an evolutionary tree constructed using the notion that respiratory
complexity and efficiency progressively increased throughout the evolutionary process. The analysis suggests that oxygenic
respiration is quite an old process and, in fact, predates nitrogenic respiration as well as reaction-center photosynthesis.
Received: 11 June 1997 / Accepted: 30 October 1997 相似文献
15.
Evidence is available showing that the coupling efficiency of the proton pump in cytochrome c oxidase of mitochondria can under certain conditions decrease significantly below the maximum attainable value. The view is developed that slips in the proton pump of cytochrome c oxidase represent an intrinsic switch mechanism which regulates the relative contribution of energy transfer and respiratory protection against oxygen toxicity by the oxidase. 相似文献
16.
《Bioscience, biotechnology, and biochemistry》2013,77(7):1756-1763
Acidithiobacillus ferrooxidans AP19-3, ATCC 23270, and MON-1 are mercury-sensitive, moderately mercury-resistant, and highly mercury-resistant strains respectively. It is known that 2,3,5,6-tetramethyl-p-phenylendiamine (TMPD) and reduced cytochrome c are used as electron donors specific for cytochrome c oxidase. Resting cells of strain MON-1 had TMPD oxidase activity and volatilized metal mercury with TMPD as an electron donor. Cytochrome c oxidase purified from strain MON-1 reduced mercuric ions to metalic mercury with reduced mammalian cytochrome c as well as TMPD. These mercury volatilization activities with reduced cytochrome c and TMPD were completely inhibited by 1 mM NaCN. These results indicate that cytochrome c oxidase is involved in mercury reduction in A. ferrooxidans cells. The cytochrome c oxidase activities of strains AP19-3 and ATCC 23270 were completely inhibited by 1 μM and 5 μM of mercuric chloride respectively. In contrast, the activity of strain MON-1 was inhibited 33% by 5 μM, and 70% by 10 μM of mercuric chloride, suggesting that the levels of mercury resistance in A. ferrooxidans strains correspond well with the levels of mercury resistance of cytochrome c oxidase. 相似文献
17.
Alexander A. Konstantinov 《Journal of bioenergetics and biomembranes》1998,30(1):121-130
Cytochrome oxidase (COX) is considered to integrate in a single enzyme two consecutive mechanistically different redox activities--oxidase and peroxidase--that can be catalyzed elesewhere by separate hemoproteins. From the viewpoint of energy transduction, the enzyme is essentially a proton pumping peroxidase with a built-in auxiliary eu-oxidase module that activates oxygen and prepares in situ H2O2, a thermodynamically efficient but potentially hazardous electron acceptor for the proton pumping peroxidase. The eu-oxidase and peroxidase phases of the catalytic cycle may be performed by different structural states of COX. Resolution of the proton pumping peroxidase activity of COX and identification of individual charge translocation steps inherent in this reaction are discussed, as well as the specific role of the two input proton channels in proton translocation. 相似文献
18.
NADPH-cytochrome P450 reductase was purified to apparent homogeneity and cytochrome P450 partially purified from whole rat brain. Purified reductase from brain was identical to liver P450 reductase by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and western blot techniques. Kinetic studies using cerebral P450 reductase reveal Km values in close agreement with those determined with enzyme purified from rat liver. Moreover, the brain P450 reductase was able to function successfully in a reconstituted microsomal system with partially purified brain cytochrome P450 and with purified hepatic P450c (P450IA1) as measured by 7-ethoxycoumarin and 7-ethoxyresorufin O-deethylation. Our results indicate that the reductase and P450 components may interact to form a competent drug metabolism system in brain tissue. 相似文献
19.
Direct sequencing of cytochrome oxidase subunit III (coxIII) mRNA with a specific primer confirms RNA editing in sunflower (Helianthus annus) mitochondria. Six instances of mRNA editing could be verified, one of these specific to this species. All the editing events involve C to U transitions in the coxIII mRNA causing codon changes that lead to amino acids better conserved in evolution than those encoded in the genomic DNA. This observation confirms RNA editing to be widespread in higher plant mitochondria. 相似文献