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)

Cytochrome oxidase is a multisubunit, intrinsic membrane protein with a complex function that includes oxidation of cytochrome c, reduction of oxygen and generation of a membrane potential. To clarify the relationship of its normal function to protein and membrane structure, we have examined the kinetic behavior of rat liver cytochrome oxidase in the intact inner mitochondrial membrane and in detergent solubilized states. Dissolution of rat liver mitochondrial membranes alters the kinetic parameters of the oxidase in a manner dependent in part on the dispersing agent, and characterized by a large increase in maximal activity which is not attributable to exposure of more oxidase or diminished affinity for cytochrome c. The most profound effect of solubilization of the membrane is seen on the low affinity reaction of cytochrome c, suggesting that the electron transfer pathway from this site to oxygen is sensitive to alterations in hydrophobic interactions within the oxidase. Purified rat liver and beef heart oxidase exists predominantly in a monodisperse, 300 kilodalton form in laurylmaltoside (Rosevear et al., 1980). However, a smaller, 130 kd species that exhibits high turnover rates equal to the 300 kd form is detected in some beef heart preparations, implying that the dimer may not be essential for high activity. Radiation inactivation studies on purified oxidase reveal a molecular weight for the functional unit of approximately 70 kd. It is concluded that less than a complete set of subunits may be sufficient for both normal binding of cytochrome c and rapid electron transfer to oxygen.
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PMID:The active form of cytochrome c oxidase: effects of detergent, the intact membrane, and radiation inactivation. 627 25

The reactivation of delipidated cytochrome oxidase depends on the reformation of "annular lipids", which is tightly bounded to the enzyme molecule. In the restoration of oxidase activity, the efficiencies of phospholipids with different polar head groups decrease in this order: PS greater than DPG greater than PI greater than PA greater than PG greater than PC, PE and in the case of phosphatidylcholines with different acyl chain the order is DOPC greater than LPC greater than PC greater than DPPC, DSPC. Therefore both the polar head group and the acyl chain of phospholipids must be considered in the reactivation process. The existence and the specificity of "annular lipids" obviously influence the incorporation of cytochrome oxidase into liposomes. When acidic phospholipids are used as "annular lipids", the effectiveness of reconstitution decreases in this order: PI greater than PS greater than DPG greater than PA, PG. Divalent metallic cations would facilitate the cytochrome oxidase reconstitution, but their effects depend on the composition of "annular lipids". Using dialysis method Ca2+ and Mg2+ could facilitate the incorporation into liposomes of the enzymes having PS or DOPC as their "boundary lipids". A comparison between the effects of different metallic cations on incorporation of cytochrome oxidase also shows that, with PI as "annular lipids", the effectiveness of different cations on incorporation by incubation method decreases in this order: Ca2+ greater than Mg2+ greater than Mn2+, Sr2+ greater than La3+. Apparently, the effect of metallic cations on incorporation cannot be interpreted by considering only the neutralization of the negative charged groups on membrane protein and lipids.
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PMID:Studies on the incorporation of membrane proteins into liposomes: --effect of "boundary lipids" on reconstitution of pig heart mitochondrial cytochrome oxidase into liposomes. 628 66

Using a polarographic method, we studied the inhibition of mitochondrial electron transport at the cytochrome c oxidase site caused by eight local anaesthetics. The diversity of the types of inhibition observed indicate the importance of electrostatic interactions between the anaesthetic molecules and the membrane protein. A linear relationship was recognized between the anaesthetic activity of infiltration and the affinity for the enzyme. We also observed a significant relationship between this affinity and the octanol-water partition coefficient. This result suggests that lipophilic interactions are involved in cytochrome oxidase-anaesthetic binding. We tried to establish a parallel between this binding and the mechanism of anaesthesia involving the nerve membrane proteins.
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PMID:Inhibition of cytochrome oxidase activity by local anaesthetics. 631 7

The post-natal development of interscapular brown adipose tissue (BAT) was studied in the guinea pig by monitoring changes in DNA, triglycerides and mitochondrial protein as well as the activity of cytochrome oxidase and atractyloside insensitive GDP-binding. The results demonstrate that neonatal brown fat develops into a tissue with the gross characteristics of white adipose tissue. In this respect the post-natal development of guinea pig BAT is analogous to that of the tissue in man. Furthermore the apparent transformation is not irreversible since cold exposure (+4 degrees C) of adult guinea pigs for six weeks resulted in restoration of cytochrome oxidase, GDP-binding, etc, to levels characteristic of neonatal BAT. However, the interscapular fat pad temperature response to noradrenaline and the presence of 32 000 mol. wt mitochondrial inner membrane protein indicate that the tissue retains thermogenic activity even in warm acclimated adult guinea pigs.
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PMID:Post-natal development of interscapular (brown) adipose tissue in the guinea pig: effect of environmental temperature. 651 Nov 66

Radiolabel from [3H]myristic acid was incorporated by Neurospora crassa into the core catalytic subunit 1 of cytochrome c oxidase (EC 1.9.3.1), as indicated by immunoprecipitation. This modification of the subunit, which was specific for myristic acid, represents an uncommon type of myristoylation through an amide linkage at an internal lysine, rather than an N-terminal glycine. The [3H]myristate, which was chemically recovered from the radiolabeled subunit peptide, modified an invariant Lys-324, based upon analyses of proteolysis products. This myristoylated lysine is found within one of the predicted transmembrane helices of subunit 1 and could contribute to the environment of the active site of the enzyme. The myristate was identified by mass spectrometry as a component of mature subunit 1 of a catalytically active, purified enzyme. To our knowledge, fatty acylation of a mitochondrially synthesized inner-membrane protein has not been reported previously.
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PMID:Cytochrome c oxidase in Neurospora crassa contains myristic acid covalently linked to subunit 1. 756 96

Rotenone-poisoned rat liver mitochondria energized by succinate addition, after a 5-min period of preincubation in presence of 10 microM Ca2+, produce H2O2 at much faster rates, undergo extensive swelling, and are not able to retain the membrane potential and accumulated Ca2+. Similar results were obtained when a suspension of rat liver mitochondria preincubated in anaerobic medium for 5 min was reoxygenated. The addition of either ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid, ruthenium red, catalase, or dithiothreitol, just before succinate or O2 addition, prevented mitochondrial swelling, indicating the involvement of Ca2+, reactive oxygen species, and oxidation of membrane protein thiols in this process of membrane permeabilization. Inhibition of mitochondrial swelling by cyclosporin A suggests that the membrane alterations observed under these experimental conditions are related to opening of the permeability transition pore. The presence of carbonyl cyanide p-trifluoromethoxyphenylhydrazone, which prevents Ca2+ cycling across the membrane, did not inhibit mitochondrial swelling when Ca2+ influx into the mitochondrial matrix was driven by a high Ca2+ gradient. When rotenone plus antimycin A-poisoned mitochondria were energized by N,N,N',N'-tetramethyl-p-phenylenediamine, which reduces respiratory chain complex IV, mitochondrial swelling did not occur, unless succinate, which reduces coenzyme Q, was also added. It is concluded that reduced coenzyme Q is the electron source for oxygen radical production during Ca(2+)-stimulated oxidative damage of mitochondria.
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PMID:Ca(2+)-induced mitochondrial membrane permeabilization: role of coenzyme Q redox state. 763 41

While a considerable amount of literature deals with the structural energetics of water-soluble proteins, relatively little is known about the forces that determine the stability of membrane proteins. Similarly, only a few membrane protein structures are known at atomic resolution, although new structures have recently been described. In this article, we review the current knowledge about the structural features of membrane proteins. We then proceed to summarize the existing literature regarding the thermal stability of bacteriorhodopsin, cytochrome-c oxidase, the band 3 protein, Photosystem II and porins. We conclude that a fundamental difference between soluble and membrane proteins is the high thermal stability of intrabilayer secondary structure elements in membrane proteins. This property manifests itself as incomplete unfolding, and is reflected in the observed low enthalpies of denaturation of most membrane proteins. By contrast, the extramembranous parts of membrane proteins may behave much like soluble proteins. A brief general account of thermodynamics factors that contribute to the stability of water soluble and membrane proteins is presented.
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PMID:Forces and factors that contribute to the structural stability of membrane proteins. 785 60

Subunit c is normally present as an inner mitochondrial membrane component of the F0 sector of the ATP synthase complex, but in the late infantile form of neuronal ceroid-lipofuscinosis (NCL) it was also found in lysosomes in high concentrations. The rate of degradation of subunit c as measured by pulse-chase and immunoprecipitation showed a marked delay of degradation in patients' fibroblasts with late infantile form of NCL. There were no significant differences between control cells and cells with disease in the degradation of cytochrome oxidase subunit IV, an inner membrane protein of mitochondria. Measurement of labeled subunit c in mitochondrial and lysosomal fractions showed that the accumulation of labeled subunit c in the mitochondrial fraction can be detected before lysosomal appearance of radioactive subunit c, suggesting that subunit c accumulated as a consequence of abnormal catabolism in the mitochondrion and is transferred to lysosomes through an autophagic process. The biosynthetic rate of subunit c and mRNA levels for P1 and P2 genes that code for it were almost the same in both control and patient cells. These findings suggest that a specific failure in the degradation of subunit c after its normal inclusion in mitochondria and its consequent accumulation in lysosomes.
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PMID:Abnormal degradative pathway of mitochondrial ATP synthase subunit c in late infantile neuronal ceroid-lipofuscinosis (Batten disease). 766 41

Insulin increases the synthesis of mitochondrial proteins in the isolated perfused heart and total cell protein synthesis in neonatal cardiac myocytes. Since carnitine-dependent fatty acid oxidation is modulated by insulin in a variety of tissues, the effects of 1.7 microM insulin on the mitochondrial enzyme(s), carnitine palmitoyltransferase (malonyl-CoA-sensitive CPT-I and the matrix-facing CPT-II), were studied in neonatal rat cardiac myocytes cultured in the absence of serum. Following incubation in serum-free medium, there is a four-fold increase in the I50 of CPT-I for malonyl-CoA (3.8 microM) compared to cells cultured in serum-free medium to which insulin has been added (I50 = 0.8 microM). CPT-I activity in the insulin-supplemented, serum-free cultures is 57% higher (P < 0.002) than CPT-I activity in cells cultured in the absence of insulin; CPT-II activity is also significantly increased (P < 0.01) in the presence of insulin. Since CPT-II is an inner membrane protein, the CPT response to insulin may be coordinately regulated with other mitochondrial activities. Similar to CPT, cytochrome oxidase activity of cardiac myocytes in serum-free medium is increased 33% by insulin. Consistent with this finding, both CPT-II and cytochrome oxidase mRNA expression is elevated over control in the presence of insulin. CPT-II activity increases significantly only at very high insulin concentrations (1.7 microM), suggesting a role for insulin-like growth factor pathway. When myocytes are cultured in the presence of 1.7 microM insulin and then transferred to an insulin-free medium, subsequent addition of insulin does not stimulate uptake of deoxyglucose. These results suggest that the response of CPT to insulin is mediated by insulin-like growth factor activity and not by cellular glucose availability. The response of CPT to insulin does not appear to be mediated by the protein kinase C pathway since CPT-II activity is not reduced by the protein kinase C inhibitor, chelerythrine. Insulin significantly increases protein synthesis in the neonatal cardiac myocyte and in isolated mitochondria by increasing incorporation of labelled amino acid into total myocyte and/or mitochondrial protein. The degradation rate of radiolabelled protein in cardiac myocytes cultured in the presence of insulin is not different from that of insulin-deprived cells. The data suggest that insulin can affect the activity and expression of mitochondrial proteins, e.g., CPT, through the insulin-like growth factor-I pathway in neonatal cardiac myocytes.
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PMID:Insulin-associated changes in carnitine palmitoyltransferase in cultured neonatal rat cardiac myocytes. 776 Mar 80

Cytochrome c-551 is a lipoprotein of about 10500 Da, found in thermophilic Bacillus PS3 grown under air-limited conditions. An expression vector was constructed from a structural gene of PS3 cytochrome c-551, synthetic oligonucleotide as a promoter for Bacillus stearothermophilus and a shuttle vector for Escherichia coli and B. stearothermophilus. The transformed cells of B. stearothermophilus K1041 expressed cytochrome c-551 as much as 5 nmol/mg membrane protein. The effects of over-expression on the host cells are analyzed; a slightly slower growth rate and an increased synthesis of cytochrome oxidase (about twofold) occurred. Over-expressed (4-10-fold) cytochrome c-551 were purified and its properties were examined to know whether the protein is processed as in PS3 cells grown under air-limited conditions. The molecular mass determination and treatment with Rhizopus lipase suggested that the same processes, cleavage of signal peptidase, blocking of the N-terminal group and acylation of glycerol residue by two fatty acids, took place in the over-expression system. Fatty acylation seems useful for the cytochrome c to be effectively oxidized.
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PMID:Over-expression of membrane-bound cytochrome c-551 from thermophilic Bacillus PS3 in Bacillus stearothermophilus K1041. 780 47


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