The role of H2O2 generation in perfused rat liver and the reaction of catalase compound I and hydrogen donors

Oshino, Nozomu; Chance, Britton; Sies, Helmut; Bücher, Theodor

doi:10.1016/0003-9861(73)90040-4

Cited by 263 publications

(107 citation statements)

References 31 publications

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“…H 2 O 2 is a normal cellular metabolite that is continuously generated and maintained at low concentrations by a number of peroxidases. Techniques based on the spectral and kinetic properties of catalase (137,162) provided the first reasonable estimates of H 2 O 2 concentration in mammalian cells. Importantly, these studies showed that steady-state H 2 O 2 production occurs at rates that maintain nanomolar concentrations; during detoxification, rates can be stimulated in the liver Right, Grx uses reducing equivalents from GSH, which is maintained by GSSG reductase, to reduce sulfur switches designated as PrA, PrB, etc.…”

Section: Oxidative Stress As a Disruption Of Redox Signaling And Controlmentioning

confidence: 99%

Radical-free biology of oxidative stress

Jones¹

2008

American Journal of Physiology-Cell Physiology

983

815

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Free radical-induced macromolecular damage has been studied extensively as a mechanism of oxidative stress, but large-scale intervention trials with free radical scavenging antioxidant supplements show little benefit in humans. The present review summarizes data supporting a complementary hypothesis for oxidative stress in disease that can occur without free radicals. This hypothesis, which is termed the "redox hypothesis," is that oxidative stress occurs as a consequence of disruption of thiol redox circuits, which normally function in cell signaling and physiological regulation. The redox states of thiol systems are sensitive to twoelectron oxidants and controlled by the thioredoxins (Trx), glutathione (GSH), and cysteine (Cys). Trx and GSH systems are maintained under stable, but nonequilibrium conditions, due to a continuous oxidation of cell thiols at a rate of about 0.5% of the total thiol pool per minute. Redox-sensitive thiols are critical for signal transduction (e.g., H-Ras, PTP-1B), transcription factor binding to DNA (e.g., Nrf-2, nuclear factor-B), receptor activation (e.g., ␣IIb␤3 integrin in platelet activation), and other processes. Nonradical oxidants, including peroxides, aldehydes, quinones, and epoxides, are generated enzymatically from both endogenous and exogenous precursors and do not require free radicals as intermediates to oxidize or modify these thiols. Because of the nonequilibrium conditions in the thiol pathways, aberrant generation of nonradical oxidants at rates comparable to normal oxidation may be sufficient to disrupt function. Considerable opportunity exists to elucidate specific thiol control pathways and develop interventional strategies to restore normal redox control and protect against oxidative stress in aging and age-related disease.thioredoxin; glutathione; cysteine; hydrogen peroxide; redox signaling; protein thiol ONE OF THE GREAT REDOX BIOLOGISTS of the past century, Howard S. Mason, professed that to advance science, a scientist must interpret observations at the limit of their meaning. The present review of the redox biology of thiol systems addresses the possibility that disruption of the function and homeostasis of thiol systems is the most central feature of oxidative stress that contributes to mechanisms of aging and age-related disease. I have termed this the "redox hypothesis" to facilitate distinction from free radical hypotheses.Many proteins contain redox-sensitive thiols, and reactions of thiol systems occur largely by nonradical two-electron transfers. Accumulating data show that central thiol-disulfide couples are maintained under nonequilibrium conditions in biological systems. This presents a condition wherein changes in abundance and distribution of redox catalysts and changes in rates of generation of relevant oxidants (e.g., peroxides) and precursors for NADPH supply can account for pathological effects of oxidative stress through altered functions of enzymes, receptors, transporters, transcription factors, and structural elements, without free ra...

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Section: Oxidative Stress As a Disruption Of Redox Signaling And Controlmentioning

confidence: 99%

Radical-free biology of oxidative stress

Jones¹

2008

American Journal of Physiology-Cell Physiology

983

815

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“…An estimation of effectiveness of the intracellular sources of H 2 O 2 in rat liver indicates that mitochondria contribute about 40% of the [ H 2 O 2 ]ss in cytosol; an equivalent 40% is provided by the well developed liver endoplasmic reticulum (13,14,20). In other tissues with lower content of endoplasmic reticulum, such as lung, heart and muscle, the mitochondrial contribution to cytosolic H 2 O 2 is about 70%, 92% and 96%, respectively.…”

Section: Mitochondrial Generation Of H 2 Omentioning

confidence: 99%

Mitochondrial Production of Hydrogen Peroxide Regulation by Nitric Oxide and the Role of Ubisemiquinone

Boveris

Cadenas

2000

IUBMB Life

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“…Williams-Smith, unpublished observation). However, there is no optical evidence for the formation of this compound in intact perfused liver (Oshino et al, 1973) and our detection of catalase-formate in aerobic and anaerobic diseased liver would make its existence highly unlikely since formic acid should reduce the steady state concentration of catalase compound 1, through which compound II is formed, and since formic acid speeds the spontaneous reversal of compound II to free catalase (Nicholls, 1961a (Thamm et al, 1971). However, the similarity of the 1 and 2 min comparisons might argue against any effects being due to raised formate levels.…”

Section: Resultsmentioning

confidence: 99%

“…Catalase is largely located within the peroxisome, where it constitutes -50% of the protein in this organelle (de Duve & Baudhin, 1966). In a series of elegant optical studies it has been possible to quantitate the substrate and oxygen dependence of hydrogen peroxide production and to estimate the extent to which the two types of catalase reactions take place (Oshino et al, 1973(Oshino et al, , 1975 (Biggs, 1973 (Churchill, 1968 (Saha et al, 1964), whose heme concentration was determined optically using an extinction coefficient at 405 nm of 9.5 x 104cm-I M -1 (Nicholls, 1961a). To correct for small differences in the catalase EPR lineshapes from the two sources, the spectra were computer simulated using a program which incorporated intensity factors (Aasa & Vanngard, 1975) to correct for the field dependence of transition probability, and in which linewidths were varied in the same way as a first order hyperfine interaction.…”

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confidence: 99%