Mechanism of control of cytochrome oxidase activity by the electrochemical-potential gradient.

Brunori, Maurizio; Sarti, Paolo; Colosimo, Alfredo; Antonini, Giovanni; Malatesta, Francesco; Jones, M G; Wilson, Moira

doi:10.1002/j.1460-2075.1985.tb03940.x

Cited by 60 publications

(47 citation statements)

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“…when valinomycin and K t are present) and the analysis of transient and steady-state kinetic experiments carried out with cytochrome oxidase vesicles following the time course of oxidation of ferrocytochrome c added externally, have led us to propose a model for the control of cytochrome oxidase activity [20,21]. According to this model, cytochrome oxidase may exist in two conforniational states which are in rapid equilibrium: both states of the enzyme, designated as P and S, are catalytically competent, being capable of carrying out electron transfer with proper stoichiometry.…”

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Cytochrome-c oxidase. Subunit structure and proton pumping

Brunori¹,

et al. 1987

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Cytochrome-c oxidase. Subunit structure and proton pumping

Brunori¹,

et al. 1987

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“…The electrongradient controls electron flow, not only from cytochrome c to cytochrome a, but also from the later to cytochrome a3/ Cu,, which is also controlled by the pH of the matrix space, and finally from the binuclear site to oxygen (Capitanio et al, 1990); the electrical gradient is the major regulator of cytochrome c oxidase which acts by shifting the equilibrium between two conformational states of the enzyme, characterized by different catalytic rates. These conformational states were called P (pumping), characterized by a high turnover rate, and as S (slipping), characterized by a slow turnover rate and failure of the proton pump (Brunori et al, 1985;Antonini et al, 1991). In this work, it has been assumed that P and S correspond to states i and ii, respectively.…”

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confidence: 99%

“…A variety of techniques have been developed to estimate the dependence of cytochrome c oxidase activity on the oxygen concentration, including measurements of cytochrome redox states by spectrophotometry and oxygen consumption by either polarography or oxygen-quenched phosphorescence in different types of normal and tumor mammalian cells, including hepatocytes, cardiac myocytes, renal epithelial cells, sarcoma 180 ascites tumor cells and neuroblastoma cells or isolated mitochondria (Wilson et al, 1979(Wilson et al, , 1988; Jones et al, 1985;Kennedy and Jones, 1986; Robiolo et al, 1989). Unfortunately, a large discrepancy in the experimental results have been reported since the oxygen concentration values for halfmaximal respiration vary several fold.…”

Section: Time Dependence Of Oxygen Consumption By Ascites Tumor Cellsmentioning

confidence: 99%

“…The rate of oxygen consumption is a measure of the rate of ATP synthesis (Wilson et al, 1979). It has been suggested that the rate-controlling step of mitochondrial energy transduction occurs through a irreversible reaction catalyzed by the cytochrome c oxidase (Erecinska and Wilson, 1978;Brunori et al, 1985). The overall reaction is as follows (Costa et al, 1984): 4 ferrocytochrome c + 4H+ + O2 + 4 ferricytochrome c + 2HZO.…”

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“…This experimental setting is not necessarily analogous to the physiological situation where, in spite of a continuous oxygen supply, a substantial oxygen concentration gradient exists from blood to the mitochondrial inner membrane (Kennedy and Jones, 1986). Furthermore, the oxygen concentration in the interior of the cell is most probably not uniform (Jones, et al, 1985). Electron carriers of the mitochondrial respiratory chain become more reduced as soon as the oxygen partial pressure is lowered from that prevailing in air to that prevailing in tissues, without causing a change in the respiratory rate (Forman and Wilson, 1982).…”

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The oxygen dependence of the mitochondrial respiration rate in ascites tumor cells

Ferreira

1992

European Journal of Biochemistry

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The effect of the oxygen concentration on the rate of oxygen consumption by 786 and TA3 ascites tumor cell lines has been determined under steady-flow conditions with a membraneless fastresponding O2 electrode and using ascorbate and N,N,N',N'-tetramethyl-p-phenylenediamine as electron donors. The reaction was initiated by rapid injection of O2 into anaerobically incubated test system. The time-dependence of the intact cell respiration showed three distinct phases; an early very fast but short duration phase, a subsequent slow phase that prevailed for most of the reaction period and a third phase which preceded the reestablishment of anaerobiosis. Kinetic analysis of the reaction indicated a linkage between the catalytic efficiency and the transmembrane electrochemical potential. The rates of O2 uptake, obtained in the presence of both protonophores and ionophores, were monotonic and pseudo-first order over 90% of the course of O2 consumption. Extrapolation of the observed rates to zero time, at which zero A p H + and thus constant flow prevails, was used to calculate the oxygen concentration for the half-maximal respiratory rate, which was found to be in the range 1.55 -2.10 pM 02. No noticeable variation in the value of this kinetic parameter was found between the two cell lines used. Possible reasons for discrepancies in published reports on the oxygen dependence of the cytochrome c oxidase activity in various mitochondrial and reconstituted systems are discussed.ATP is required by living organisms to provide energy for biosynthesis, transport and mechanical work. It would seem that all tumor cells do not obtain the same proportion of ATP from mitochondrial and glycolytic reactions. The slowgrowth-rate and intermediate-growth-rate classes of tumor cells, as well as many normal tissues, obtain the bulk of their ATP from mitochondrial oxidative phosphorylation (more than 90% of the total), whereas rapidly growing tumors, even in the presence of a high glucose concentration, can obtain noticeable amounts of ATP from both sources, but with the higher proportion of ATP still being derived from oxidative phosphorylation (over 50%) (Pedersen, 1978). Moreover, accumulated evidence indicate that oxidation of glutamine is the major energy source for tumor cells, even in the presence of physiological levels of glucose (Moreadith andLehninger, 1984a, 1984b;Matsuno, 1987; Kovacevic et al., 1991). However, hexokinase bound to the mitochondria of highly glycolytic tumor cells utilises mitochondrially generated ATP rather than cytosolic ATP (Arora and Pedersen, 1988). Consequently, mitochondria from tumor cells would be the most important site for ATP synthesis.It is well established that a significant proportion of the cells in solid tumors of both rodents and human are hypoxic. Hypoxia has been identified as a factor that may affect the behavior of cancer cells, such as to limit the cure rate of standard radiotherapy and the action of some anticancer drugs in at least some types of human malignancy. Reoxygen-

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