Mitochondrial function under hypoxic conditions: The steady states of cytochrome a+a3 and their relation to mitochondrial energy states

Oshino, Nozomu; Sugano, Tsukasa; Oshino, Reiko; Chance, Britton

doi:10.1016/0005-2728(74)90176-5

Cited by 141 publications

(52 citation statements)

References 23 publications

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“…At -100°, oxygen appears to be highly dissociated from the oxidase, whereas at 23°the apparent affinity is approximately 0.05 /M (33), a ratio of nearly 104. It appears that the high affinity of cytochrome oxidase for oxygen at room temperature is due to a kinetic rather than a thermodynamic property.…”

Section: Materials Methods and Resultsmentioning

confidence: 95%

Functional intermediates in reaction of cytochrome oxidase with oxygen.

Chance¹,

Saronio²,

Leigh³

1975

Proc. Natl. Acad. Sci. U.S.A.

131

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The development of a low temperature kinetic method for the flash photolysis of the compounds of membrane-bound cytochrome as with carbon monoxide in the presence of oxygen affords evidence for three categories of functional intermediate compounds of cytochrome a3 and oxygen. The three classes are identified as follows: Compounds of Type A are considered to be "oxy" compounds of the ferrous heme. They have the composition asQ-0,. Compounds of Type B are considered to be peroxide compounds (Cu2+ass+-02. or Cul+a:,+. 02H2) or the equivalent heme Fe-Cu peroxide bridge structures. Compounds of Type C are formed from the ferricyanide pretreated oxidase and may involve higher oxidation states of the heme iron such as quadrivalent iron, and peroxide. Kinetic and equilibrium studies show these compounds to be functional in oxygen reduction in the sequence A B -cytochromes a, c, cl, etc.The observation of intermediates in enzyme-substrate interactions has led to a verification of the Michaelis-Menten theory upon which enzyme mechanisms are based (1-5). The most likely enzyme-substrate compounds (6) to be discovered first are those that are abortive, nonfunctional, or "dead-end." History tells us that Kurt Stern's (7) red enzyme-substrate compound in the catalase-ethyl hydrogen peroxide reaction was discovered only because it was inactive; the active compound was too labile (2) for the techniques at hand. Peroxidase was also found to form an inactive stable enzyme-substrate compound IV (8) which has recently been restudied by Yamazaki (9).A similar development seems to have occurred in the case of cytochrome oxidase, where Okunuki (10), Lemberg (11), Wainio (12), and others have studied what they term an "oxygenated" form of the oxidase. The possibility that the "oxygenated" form could be preceded by more active forms, just as in the case of the catalases and peroxidases, has led us to the current study.Gibson and Greenwood have studied the detergentsolubilized oxidase and have discovered a time separation of components a a, and Cu (13). However, heterogeneity is present in such preparations and thus the membrane-bound oxidase of intact mitochondria has been used in these studies.Some success with this approach was obtained in experi- Of greatest advantage in these studies was the fact that the frozen mixture of oxygen and the carbon monoxide compound of cytochrome oxidase can be chilled prior to photolysis to the point where the half-time of the reaction following photoly-

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Section: Materials Methods and Resultsmentioning

confidence: 95%

Functional intermediates in reaction of cytochrome oxidase with oxygen.

Chance¹,

Saronio²,

Leigh³

1975

Proc. Natl. Acad. Sci. U.S.A.

131

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“…Because the K m value for O 2 with respect to cytochrome oxidase is Ͻ1 mm Hg, this PO 2 level would be expected to make mitochondrial oxygen availability nonlimiting. 18 Although Mb-␦ was not detected during dobutamine infusion, it is possible that an initial period of myoglobin desaturation at the onset of increased work could have been missed. To achieve adequate sensitivity for detection of Mb-␦ required summing of 1 H NMR spectra over a period of 5 minutes.…”

Section: Myocyte Oxygenationmentioning

confidence: 99%

Myocardial Oxygenation During High Work States in Hearts With Postinfarction Remodeling

et al. 1999

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Background-Postinfarction left ventricular remodeling (LVR) is associated with reductions in myocardial high-energy phosphate (HEP) levels, which are more severe in animals that develop overt congestive heart failure (CHF). During high work states, further HEP loss occurs, which suggests demand-induced ischemia. This study tested the hypothesis that inadequate myocyte oxygen availability is the basis for these HEP abnormalities. Methods and Results-Myocardial infarction was produced by left circumflex coronary artery ligation in swine. Studies were performed in 20 normal animals, 14 animals with compensated LVR, and 9 animals with CHF. Phosphocreatine (PCr)/ATP was determined with 31 P NMR and deoxymyoglobin (Mb-␦) with 1 H NMR in myocardium remote from the infarct. Basal PCr/ATP tended to be decreased in postinfarct hearts, and this was significant in animals with CHF. Infusion of dobutamine (20 g ⅐ kg Ϫ1 ⅐ min Ϫ1 IV) caused doubling of the rate-pressure product in both normal and LVR hearts and resulted in comparable significant decreases of PCr/ATP in both groups. This decrease in PCr/ATP was not associated with detectable Mb-␦. In CHF hearts, rate-pressure product increased only 40% in response to dobutamine; this attenuated response also was not associated with detectable Mb-␦. Conclusions-Thus, the decrease of PCr/ATP during dobutamine infusion is not the result of insufficient myocardial oxygen availability. Furthermore, in CHF hearts, the low basal PCr/ATP and the attenuated response to dobutamine occurred in the absence of myocardial hypoxia, indicating that the HEP and contractile abnormalities were not the result of insufficient oxygen availability. (Circulation. 1999;99:942-948.)

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“…The apparent Km of isolated cytochrome oxidase for oxygen in the absence of Ap is about 1,UM (Petersen et al, 1976) and the apparent Km of respiration in isolated mitochondria for oxygen has been measured to be between 0.01 and 1 UM, being higher in coupled than uncoupled mitochondria (Oshino et al, 1974;Petersen et al, 1974;Wilson et al, 1979Wilson et al, , 1988. The oxygen concentration of venous blood is considerably higher than these values; thus it might be thought that cytochrome oxidase is always saturated with oxygen.…”

Section: Control By Oxygenmentioning

confidence: 99%

Control of respiration and ATP synthesis in mammalian mitochondria and cells

Brown

1992

Biochemical Journal

563

308

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We have seen that there is no simple answer to the question ‘what controls respiration?’ The answer varies with (a) the size of the system examined (mitochondria, cell or organ), (b) the conditions (rate of ATP use, level of hormonal stimulation), and (c) the particular organ examined. Of the various theories of control of respiration outlined in the introduction the ideas of Chance & Williams (1955, 1956) give the basic mechanism of how respiration is regulated. Increased ATP usage can cause increased respiration and ATP synthesis by mass action in all the main tissues. Superimposed on this basic mechanism is calcium control of matrix dehydrogenases (at least in heart and liver), and possibly also of the respiratory chain (at least in liver) and ATP synthase (at least in heart). In many tissues calcium also stimulates ATP usage directly; thus calcium may stimulate energy metabolism at (at least) four possible sites, the importance of each regulation varying with tissue. Regulation of multiple sites may occur (from a teleological point of view) because: (a) energy metabolism is branched and thus proportionate regulation of branches is required in order to maintain constant fluxes to branches (e.g. to proton leak or different ATP uses); and/or (b) control over fluxes is shared by a number of reactions, so that large increases in flux requires stimulation at multiple sites because each site has relatively little control. Control may be distributed throughout energy metabolism, possibly due to the necessity of minimizing cell protein levels (see Brown, 1991). The idea that energy metabolism is regulated by energy charge (as proposed by Atkinson, 1968, 1977) is misleading in mammals. Neither mitochondrial ATP synthesis nor cellular ATP usage is a unique function of energy charge as AMP is not a significant regulator (see for example Erecinska et al., 1977). The near-equilibrium hypothesis of Klingenberg (1961) and Erecinska & Wilson (1982) is partially correct in that oxidative phosphorylation is often close to equilibrium (apart from cytochrome oxidase) and as a consequence respiration and ATP synthesis are mainly regulated by (a) the phosphorylation potential, and (b) the NADH/NAD+ ratio. However, oxidative phosphorylation is not always close to equilibrium, at least in isolated mitochondria, and relative proximity to equilibrium does not prevent the respiratory chain, the proton leak, the ATP synthase and ANC having significant control over the fluxes. Thus in some conditions respiration rate correlates better with [ADP] than with phosphorylation potential, and may be relatively insensitive to mitochondrial NADH/NAD+ ratio.(ABSTRACT TRUNCATED AT 400 WORDS)

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Mitochondrial function under hypoxic conditions: The steady states of cytochrome a+a3 and their relation to mitochondrial energy states

Cited by 141 publications

References 23 publications

Functional intermediates in reaction of cytochrome oxidase with oxygen.

Functional intermediates in reaction of cytochrome oxidase with oxygen.

Myocardial Oxygenation During High Work States in Hearts With Postinfarction Remodeling

Control of respiration and ATP synthesis in mammalian mitochondria and cells

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