scholarly journals The control of electron flux through cytochrome oxidase

1987 ◽  
Vol 243 (2) ◽  
pp. 499-505 ◽  
Author(s):  
M P Murphy ◽  
M D Brand

1. The electron flux through cytochrome oxidase is a linear function of the net thermodynamic force across the complex over a limited range of conditions. 2. Over a wide range of conditions the electron flux is a complicated function of the percentage reduction of the cytochrome c pool and of delta psi (at low values of delta pH). 3. We have estimated the elasticities of electron flux through cytochrome oxidase to delta Eh of the redox reaction catalysed by cytochrome oxidase (or to cyt c2+/cyt c3+) and to delta psi. The elasticities varied depending on the values of delta psi and of the percentage reduction of the cytochrome c pool. 4. At intermediate rates (which may correspond to those in vivo) the electron flux through cytochrome oxidase is controlled to about the same extent by delta psi and by delta Eh.

1982 ◽  
Vol 203 (2) ◽  
pp. 483-492 ◽  
Author(s):  
M T Wilson ◽  
P Jensen ◽  
R Aasa ◽  
B G Malmström ◽  
T Vänngård

Cytochrome oxidase (EC 1.9.3.1; ferrocytochrome c:oxygen oxidoreductase) was studied during steady-state by optical and e.p.r. methods. Starting with either the ‘resting’ or the ‘pulsed’ enzyme, oxidase, cytochrome c, ascorbate and O2 were mixed and the reaction monitored optically. Tetramethylphenylenediamine was used as mediator to poise the steady-state to the desired reduction level. After mixing, the reaction was quenched by the used of rapid-freeze techniques. The e.p.r. spectra of samples captured at increasing tetramethylphenylenediamine concentrations (i.e. higher electron flux) show decreasing g = 2 (Cu A) and g = 3 (cytochrome a) signals. No Cu B or g = 6 signals (high-spin cytochrome a3) could be found during the reaction. Also, the signal with peaks at g = 1.69, 1.78 and 5 as well as the g = 12 signal was hardly detectable at higher turnover rates. The only new signal appearing during turnover is a radical signal, which is discussed in terms of a protein radical. Finally, a scheme is presented, proposing a catalytic cycle for cytochrome oxidase with respect to the O2 binding Cu B-cytochrome a3 unit.


1965 ◽  
Vol 49 (1) ◽  
pp. 163-188 ◽  
Author(s):  
Britton Chance

This paper considers the way in which the oxygen reaction described by Dr. Nicholls and the ADP control reactions described by Dr. Racker could cooperate to establish a purposeful metabolic control phenomenon in vivo. This has required an examination of the kinetic properties of the respiratory chain with particular reference to methods for determinations of oxygen affinity (Km). The constant parameter for tissue respiration is k1, the velocity constant for the reaction of oxygen with cytochrome oxidase. Not only is this quantity a constant for a particular tissue or mitochondria; it appears to vary little over a wide range of biological material, and for practical purposes a value of 5 x 107 at 25° close to our original value (20) is found to apply with adequate accuracy for calculation of Km for mammalia. The quantity which will depend upon the tissue and its metabolic state is the value of Km itself, and Km may be as large as 0.5 µM and may fall to 0.05 µM or less in resting, controlled, or inhibited states. The control characteristic for ADP may depend upon the electron flux due to the cytochrome chain (40); less ADP is required to activate the slower electron transport at lower temperatures than at higher temperatures. The affinity constants for ADP control appear to be less dependent upon substrate supplied to the system. The balance of ADP and oxygen control in vivo is amply demonstrated experimentally and is dependent on the oxygen concentration as follows. In the presence of excess oxygen, control may be due to the ADP or phosphate (or substrate), and the kinetics of oxygen utilization will be independent of the oxygen concentration. As the oxygen concentration is diminished, hemoglobin becomes disoxygenated, deep gradients of oxygen concentration develop in the tissue, and eventually cytochrome oxidase becomes partially and then completely reduced. DPN at this point will become reduced and the electron flow diminished. The rate of ATP production falls and energy conservation previously under the control of the ADP concentration will now be controlled by the diffusion of oxygen to the respiratory enzymes in the mitochondria. Under these conditions the rate of reaction of cytochrome oxidase with oxygen and the reaction of cytochromes with one another become of key importance. The rise of ADP and the depletion of energy reserves evoke glycolytic activity, and failure of biological function may result.


1981 ◽  
Vol 241 (3) ◽  
pp. F257-F262 ◽  
Author(s):  
R. S. Balaban ◽  
A. L. Sylvia

Optical spectrophotometry was used to measure changes in the oxidation-reduction state of cytochrome c oxidase in the in situ rat kidney. Alterations in the redox state of cytochrome c oxidase were monitored during variations in the amount of oxygen being delivered to the animal. Spectral analyses were performed on whole kidney, cortical tubule suspensions, and blood (the latter flowing freely through surgically implanted femoral arteriovenous shunts). Reaction spectra identified the location of the absorption maxima for reduced cytochrome c oxidase to be at approx. 605 nm. Additional spectral analysis indicated that hemoglobin oxygenation-deoxygenation changes had minimal artifactual interference on the cytochrome redox signals. The present results indicate that mitochondrial cytochrome c oxidase is not maximally oxidized in the in situ kidney of anesthetized rats at arterial oxygen in the in situ kidney of anesthetized rats at arterial oxygen tensions within the normal physiological range. The redox state of the enzyme in vivo is altered by changes in the level of inspired oxygen over a wide range. The current data are consistent with the existence of nonuniform regions of aerobic respiration occurring in the in situ kidney.


1991 ◽  
Vol 30 (01) ◽  
pp. 35-39 ◽  
Author(s):  
H. S. Durak ◽  
M. Kitapgi ◽  
B. E. Caner ◽  
R. Senekowitsch ◽  
M. T. Ercan

Vitamin K4 was labelled with 99mTc with an efficiency higher than 97%. The compound was stable up to 24 h at room temperature, and its biodistribution in NMRI mice indicated its in vivo stability. Blood radioactivity levels were high over a wide range. 10% of the injected activity remained in blood after 24 h. Excretion was mostly via kidneys. Only the liver and kidneys concentrated appreciable amounts of radioactivity. Testis/soft tissue ratios were 1.4 and 1.57 at 6 and 24 h, respectively. Testis/blood ratios were lower than 1. In vitro studies with mouse blood indicated that 33.9 ±9.6% of the radioactivity was associated with RBCs; it was washed out almost completely with saline. Protein binding was 28.7 ±6.3% as determined by TCA precipitation. Blood clearance of 99mTc-l<4 in normal subjects showed a slow decrease of radioactivity, reaching a plateau after 16 h at 20% of the injected activity. In scintigraphic images in men the testes could be well visualized. The right/left testis ratio was 1.08 ±0.13. Testis/soft tissue and testis/blood activity ratios were highest at 3 h. These ratios were higher than those obtained with pertechnetate at 20 min post injection.99mTc-l<4 appears to be a promising radiopharmaceutical for the scintigraphic visualization of testes.


1981 ◽  
Vol 45 (03) ◽  
pp. 290-293 ◽  
Author(s):  
Peter H Levine ◽  
Danielle G Sladdin ◽  
Norman I Krinsky

SummaryIn the course of studying the effects on platelets of the oxidant species superoxide (O- 2), Of was generated by the interaction of xanthine oxidase plus xanthine. Surprisingly, gel-filtered platelets, when exposed to xanthine oxidase in the absence of xanthine substrate, were found to generate superoxide (O- 2), as determined by the reduction of added cytochrome c and by the inhibition of this reduction in the presence of superoxide dismutase.In addition to generating Of, the xanthine oxidase-treated platelets display both aggregation and evidence of the release reaction. This xanthine oxidase induced aggreagtion is not inhibited by the addition of either superoxide dismutase or cytochrome c, suggesting that it is due to either a further metabolite of O- 2, or that O- 2 itself exerts no important direct effect on platelet function under these experimental conditions. The ability of Of to modulate platelet reactions in vivo or in vitro remains in doubt, and xanthine oxidase is an unsuitable source of O- 2 in platelet studies because of its own effects on platelets.


1997 ◽  
Vol 77 (02) ◽  
pp. 376-382 ◽  
Author(s):  
Bruce Lages ◽  
Harvey J Weiss

SummaryThe possible involvement of secreted platelet substances in agonist- induced [Ca2+]i increases was investigated by comparing these increases in aspirin-treated, fura-2-loaded normal platelets and platelets from patients with storage pool deficiencies (SPD). In the presence and absence of extracellular calcium, the [Ca2+]i response induced by 10 µM ADP, but not those induced by 0.1 unit/ml thrombin, 3.3 µM U46619, or 20 µM serotonin, was significantly greater in SPD platelets than in normal platelets, and was increased to the greatest extent in SPD patients with Hermansky-Pudlak syndrome (HPS), in whom the dense granule deficiencies are the most severe. Pre-incubation of SPD-HPS and normal platelets with 0.005-5 µM ADP produced a dose-dependent inhibition of the [Ca2+]i response induced by 10 µ M ADP, but did not alter the [Ca2+]i increases induced by thrombin or U46619. Within a limited range of ADP concentrations, the dose-inhibition curve of the [Ca2+]i response to 10 µM ADP was significantly shifted to the right in SPD-HPS platelets, indicating that pre-incubation with greater amounts of ADP were required to achieve the same extent of inhibition as in normal platelets. These results are consistent with a hypothesis that the smaller ADP-induced [Ca2+]i increases seen in normal platelets may result from prior interactions of dense granule ADP, released via leakage or low levels of activation, with membrane ADP receptors, causing receptor desensitization. Addition of apyrase to platelet-rich plasma prior to fura-2 loading increased the ADP-induced [Ca2+]i response in both normal and SPD-HPS platelets, suggesting that some release of ADP derived from both dense granule and non-granular sources occurs during in vitro fura-2 loading and platelet washing procedures. However, this [Ca2+]i response was also greater in SPD-HPS platelets when blood was collected with minimal manipulation directly into anticoagulant containing apyrase, raising the possibility that release of dense granule ADP resulting in receptor desensitization may also occur in vivo. Thus, in addition to enhancing platelet activation, dense granule ADP could also act to limit the ADP-mediated reactivity of platelets exposed in vivo to low levels of stimulation.


2019 ◽  
Vol 2 (2) ◽  
pp. 1-21 ◽  
Author(s):  
Elina Mitra ◽  
Bharati Bhattacharjee ◽  
Palash Kumar Pal ◽  
Arnab Kumar Ghosh ◽  
Sanatan Mishra ◽  
...  

Cadmium (Cd) is a notorious environmental pollutant known for its wide range of toxicities to organisms. Thus, the present study is designed to examine whether melatonin, a potent antioxidant, protects against Cd-induced oxidative damage in the heart, liver and kidney of rats. Cd treatment at a dose of 0.44 mg/kg for 15 days caused severe damage in all these organs. These included significantly increased activities of SGPT, SGOT, lactate dehydrogenase- 1 and 5 and ALP and levels of total lactate, creatinine, lipid peroxidation, protein carbonyl content and reduced glutathione while the activities of superoxide dismutases, catalase, glutathione peroxidase, glutathione reductase and glutathione-S-transferase along with mitochondrial pyruvate dehydrogenase, isocitrate dehydrogenase, α-keto glutarate dehydrogenase, succinate dehydrogenase, NADH-cytochrome-c-oxidoreductase and cytochrome-c-oxidase were significantly reduced by Cd. However, if melatonin was given orally 30 min before Cd injection, all these alterations induced by Cd were significantly preserved by melatonin. Histological observations also demonstrated that Cd exposure caused cellular lesions, promoting necrotic or apoptotic changes. Notably, all these changes were significantly protected by melatonin. The results suggest that melatonin is a beneficial molecule to ameliorate Cd-induced oxidative damage in the heart, liver and kidney tissues of rats with its powerful antioxidant capacity, heavy metal chelating activity and competition of binding sites with Cd to the GSH and catalase.


Food Industry ◽  
2020 ◽  
Vol 5 (1) ◽  
pp. 23-31
Author(s):  
Sergey Urubkov ◽  
Svetlana Khovanskaya ◽  
Ekaterina Pyrieva ◽  
Olga Georgieva ◽  
Stanislav Smirnov

Diet therapy is one of the main approaches to the treatment of a wide range of diseases of the digestive system. The treatment effectiveness of celiac disease depends on how strictly the patient adheres to a gluten-free diet. It is often disrupted due to the limited range of recommended foods and dishes, especially for children who are particularly sensitive to dietary restrictions. In this case, the development of new types of specialized gluten-free products is relevant, allowing to expand the diet both in terms of nutritional value and taste diversity. This study concerns the recipe developments of dry gluten-free mixtures using rice and amaranth with the inclusion of fruit and vegetable and berry raw materials intended for the nutrition of children over three years old suffering from celiac disease. When developing the recipes, researchers used various combinations of rice and amaranth flour, as well as fruit and vegetable powders. The rice flour composition varied in the range from 15 to 75%; amaranth – from 15 to 45%; fruit and vegetable and berry powders – up to 10%. The finished product was gluten-free cookies, muffins, pancakes made of rice and amaranth. Organoleptic evaluation showed that the studied samples of gluten-free cookies have high quality characteristics, have a pleasant taste and aroma. According to the calculated data, specialized gluten-free dry mixtures intended for children over three years with celiac disease can serve as an important source of: vegetable carbohydrates – from 26.81 to 55.19 g / 100g of finished products; protein – from 4.06 to 11.82 g/100g of finished products; dietary fiber – from 3.82 to 6.36 g/100g of finished products; and energy – from 158.12 to 333.96 kcal/100g of finished products) The developed recipess of gluten-free products can help to provide children with an adequate amount of nutrients and energy.


Author(s):  
Roohi Mohi-ud-din ◽  
Reyaz Hassan Mir ◽  
Prince Ahad Mir ◽  
Saeema Farooq ◽  
Syed Naiem Raza ◽  
...  

Background: Genus Berberis (family Berberidaceae), which contains about 650 species and 17 genera worldwide, has been used in folklore and various traditional medicine systems. Berberis Linn. is the most established group among genera with around 450-500 species across the world. This comprehensive review will not only help researchers for further evaluation but also provide substantial information for future exploitation of species to develop novel herbal formulations. Objective: The present review is focussed to summarize and collect the updated review of information of Genus Berberis species reported to date regarding their ethnomedicinal information, chemical constituents, traditional/folklore use, and reported pharmacological activities on more than 40 species of Berberis. Conclusion: A comprehensive survey of the literature reveals that various species of the genus possess various phytoconstituents mainly alkaloids, flavonoid based compounds isolated from different parts of a plant with a wide range of pharmacological activities. So far, many pharmacological activities like anti-cancer, anti-hyperlipidemic, hepatoprotective, immunomodulatory, anti-inflammatory both in vitro & in vivo and clinical study of different extracts/isolated compounds of different species of Berberis have been reported, proving their importance as a medicinal plant and claiming their traditional use.


2019 ◽  
Vol 20 (12) ◽  
pp. 1227-1243
Author(s):  
Hina Qamar ◽  
Sumbul Rehman ◽  
D.K. Chauhan

Cancer is the second leading cause of morbidity and mortality worldwide. Although chemotherapy and radiotherapy enhance the survival rate of cancerous patients but they have several acute toxic effects. Therefore, there is a need to search for new anticancer agents having better efficacy and lesser side effects. In this regard, herbal treatment is found to be a safe method for treating and preventing cancer. Here, an attempt has been made to screen some less explored medicinal plants like Ammania baccifera, Asclepias curassavica, Azadarichta indica, Butea monosperma, Croton tiglium, Hedera nepalensis, Jatropha curcas, Momordica charantia, Moringa oleifera, Psidium guajava, etc. having potent anticancer activity with minimum cytotoxic value (IC50 >3μM) and lesser or negligible toxicity. They are rich in active phytochemicals with a wide range of drug targets. In this study, these medicinal plants were evaluated for dose-dependent cytotoxicological studies via in vitro MTT assay and in vivo tumor models along with some more plants which are reported to have IC50 value in the range of 0.019-0.528 mg/ml. The findings indicate that these plants inhibit tumor growth by their antiproliferative, pro-apoptotic, anti-metastatic and anti-angiogenic molecular targets. They are widely used because of their easy availability, affordable price and having no or sometimes minimal side effects. This review provides a baseline for the discovery of anticancer drugs from medicinal plants having minimum cytotoxic value with minimal side effects and establishment of their analogues for the welfare of mankind.


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