scholarly journals Oxidation or dehydrogenation of alpha-hydroxy acids in bioenergetic metabolism: A murburn perspective

2021 ◽  
Author(s):  
Kelath Murali Manoj
Keyword(s):  
Life Forms ◽  
Oxygen Species ◽  
Redox Enzymes ◽  
Bimolecular Reactions ◽  
Oxidative Reaction ◽  
Metabolic Intermediates ◽  
Dehydrogenase Reaction ◽  
Bioenergetic Metabolism ◽  
Junction Points ◽  
Alpha Hydroxy Acids

Glycolate, lactate, malate, hydroxyglutarate and isocitrate are key alpha-hydroxyacyl metabolic intermediates found in the tissues/cells/organelles of diverse life forms. They are respectively oxidized to glyoxylate, pyruvate, oxaloacetate, ketoglutarate and oxalosuccinate in cell bioenergetic metabolism. These molecules form key junction points for divergent pathways of two to six carbon-backboned molecules (of various classes of biomolecules like carbohydrates, amino acids, etc.). The oxido-reduction of the alpha-hydroxyacyl species is traditionally believed to be carried out by reversible (de)hydrogenases, employing nicotinamide cofactors. Herein, I propose that while the reductive pathway can be mediated in a facile manner by the (de)hydrogenases, the oxidative reaction could more efficiently be coupled with murzyme activities, which employ diffusible reactive (oxygen) species (DRS/DROS/ROS). Such a murburn strategy would enable the system to tide over the highly unfavorable energy barriers of the sequential dehydrogenase reaction (~450 kJ/mol, or more!), to give kinetically viable bimolecular reactions catering to cellular needs. Further, such a scheme does not necessitate any ‘intelligent governance’ or ‘smart decision-making’ of/by the pertinent redox enzymes.

Article Commentary: Regulation of Protein Function by Residue Oxidation

2010 ◽  
Vol 3 ◽  
pp. PRI.S3327 ◽  
Author(s):  
Xing-Hai Zhang
Keyword(s):  
Protein Function ◽  
Regulatory Mechanism ◽  
Cellular Metabolism ◽  
Life Forms ◽  
Biological Macromolecules ◽  
Oxygen Species ◽  
Cellular Processes ◽  
Methionine Residues ◽  
Living Organisms ◽  
Face Generation

A majority of extant life forms require O2 to survive and thrive. Oxidation is inevitably one of the most active cellular processes and one constant challenge that living organisms must face. Generation of oxidants including reactive oxygen species is a natural consequence of cellular metabolism of all biological systems during normal life cycle under different environments. These oxidants oxidize many biological macromolecules such as proteins and affect their functions. Oxidation of specific amino acids in proteins may cause damage to protein structure and impair function, or may also activate protein activities and promote cellular metabolism. As an example, the reversible oxidation of cysteine and methionine residues has a profound impact on protein function and cellular process. A recent study that examines the effect of Met oxidation on Ser phosphorylation in a mitochondrial enzyme, pyruvate dehydrogenase, provides another demonstration that protein oxidation is an important regulatory mechanism for organisms to deal with developmental and environmental challenges throughout life processes.

Stopped-flow-optical and -ESR Study on Oxidative Reaction of Quercetin by Nitrosodisulfonate Radical as a Model of Reactive Oxygen Species

2007 ◽  
Vol 36 (11) ◽  
pp. 1388-1389 ◽  
Author(s):  
Sanuki Hodaka ◽  
Rushiru Komatsu-Watanabe ◽  
Tomoko Ideguchi ◽  
Shunji Sakamoto ◽  
Kohji Ichimori ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Reactive Oxygen ◽  
Stopped Flow ◽  
Oxygen Species ◽  
Oxidative Reaction

Oxidation Of Peroxiredoxins By Thioredoxin Inactivation Is Mediated In Arsenic Trioxide-Induced Reactive Oxygen Species Formation and Its Cytotoxicity In Acute Promyelocytic Leukemia Cells

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3858-3858
Author(s):  
Yeung-Chul Mun ◽  
Jee-Young Ahn ◽  
Eun-Sun Yoo ◽  
Jungwon Huh ◽  
Kyoung Eun Lee ◽  
...  
Keyword(s):  
Arsenic Trioxide ◽  
Acute Promyelocytic Leukemia ◽  
Promyelocytic Leukemia ◽  
Ros Generation ◽  
Oxygen Species ◽  
Redox Enzymes ◽  
Nb4 Cells ◽  
Mitochondrial Ros ◽  
Thioredoxin 1 ◽  
Induced Apoptosis

Abstract Backgrounds The Arsenic trioxide (ATO) is an effective cancer therapeutic drug for acute promyelocytic leukemia (APL). ATO exerts its effect mainly raising oxidative stress. However, not only the mechanisms of reactive oxygen species (ROS) generation by ATO but involvement of redox enzymes including peroxiredoxin (PRX) and thioredoxin (TRX) remains elusive. Aim of current study is to elucidate the mechanism of redox enzymes to elevate ROS during ATO-induced apoptosis in APL-derived NB4 cells. Methods NB4 cell line, which is one of the human acute promyelocytic leukemia cell lines, was cultured in RPMI-1640 medium supplemented with 10% FBS in CO2 humidified atmosphere at 37°C. NB4 cells were cultured with 2 μM arsenic trioxide to induce apoptosis for 16-48 hours. Apoptosis was measured by staining with 7-amino-actinomycin D (7-AAD) with flow cytometry. 2, 7-dichlrodihydro-fluorescein-diacetate (H2DCF-DA) and MitoSOX Red were used to detect cellular and mitochondrial ROS. SO2 form for PRX I, PRX II, and PRX III was detected by western blot assay using PRX SO2 form-specific antibody. Monomer/Dimer assay for PRX I, PRX II, PRX III, and TRX I was performed by western blot using non-reducing gel. Results Intracellular ROS of NB4 cells was increased significantly after 16 hour of ATO but decreased after 24 hour of ATO. Mitochondrial ROS of NB4 cells was increased significantly after 39 hour of ATO. Apoptosis of NB4 cell after ATO treatment was increased as time elapsed (24% on 16hr, 26% on 24hr, 48% on 39hr, and 60% on 48hr). Monomer, indicated active and reduced form, of peroxiredoxins was decreased and cysteine sulfinic acid (CP–SO2H) peroxiredoxins, indicated inactive and oxidized peroxiredoxins, was increased in NB4 cells after ATO treatment as time goes by. Similarily, monomer of thioredoxin-1 (active thioredoxin) was decreased and multimer of thioredoxin-1 (inactive thioredoxin) was increased in NB4 cells after ATO treatment as time elapsed. Conclusions Our data showed inactivation of peroxiredoxins by oxidation was developed during ATO-induced ROS generation and APL cell apoptosis. These peroxiredoxins oxidation was probably due to increment of reduced thioredoxin in NB4 cells after ATO treatment. These findings suggest ATO-induced anti-leukemic activity is more likely due to a TRX system-mediated cellular redox changes. Our study may provide the insights for finding novel targets in the development of new therapies, which potentiate ATO-induced apoptosis in APL cells. Disclosures: No relevant conflicts of interest to declare.

Maintaining integrity of germline DNA: individuals age, species do not

2015 ◽  
Vol 27 (6) ◽  
pp. 865 ◽  
Author(s):  
G. E. Seidel, Jr
Keyword(s):  
Genetic Material ◽  
Life Forms ◽  
Oxygen Species ◽  
Radiation Chemical ◽  
Older Parents ◽  
Disease States ◽  
Accumulation Of Damage ◽  
Germline Cells ◽  
Best Fit ◽  
Maintenance Methylation

All life forms are under constant assault, resulting in an accumulation of damage within each individual, in both somatic and germline cells. The obvious causes are: (1) mutations from radiation, chemical reactions like peroxidation and errors in replicating genetic material; (2) injury due to environmental insults, such as chemical alteration of proteins by reactive oxygen species; (3) epigenetic errors, such as failure of appropriate maintenance methylation of cytosines of DNA; and (4) numerous other problems, including retroviral invasions, inflammation and unhealthy microbiomes. Collectively, these phenomena constitute aging and/or certain disease states. Nature has developed numerous mechanisms to counteract these problems, such as proofreading enzymes, ubiquitous antioxidants and apoptotic death of unfit cells. However, none of these is completely effective. Although individuals accumulate damage, species usually do not become increasingly damaged; however, this could be one of the mechanisms for eventual extinction or evolution to a different species, the apparent fate of essentially all species. Nevertheless, germline DNA appears to remain sufficiently pristine to maintain fairly stable phenotypes over many generations. How do species avoid accumulating damage when composed of individuals that do? One broad answer seems to be reproductive redundancy followed by elimination of defects through the death of gametes, embryos, fetuses, neonates and postpubertal individuals, with the culling pressure increasing as potential parents age. Another major force appears to be evolutionary pressure; individuals that best fit the environment out-reproduce those that fit less well. What is impressive is that older and older parents continue to have offspring that are nearly as pristine as those of younger parents, even though their germline cells have continued to age. Although the offspring of old parents are not as fit, on average, as those of young parents, differences are small and, in some species, compensated for by superior parenting with accumulated experience. To conclude, it appears that species do not age, even though they are composed of individuals whose somatic and germline cells have aged.

scholarly journals Phytochemical and Antioxidant Potential of Indian Flora

2019 ◽  
Vol 8 (4S2) ◽  
pp. 1007-1010
Keyword(s):  
Ethyl Acetate Extract ◽  
Antioxidant Activities ◽  
Radical Scavenging Activity ◽  
Radical Scavenging ◽  
Antioxidant Property ◽  
Free Radical Scavenging ◽  
Oxygen Species ◽  
Oxidative Reaction ◽  
Achyranthes Aspera ◽  
Cassia Auriculata

the plant kingdom serves as a reservoir of many organic compounds that have been used for many therapeutic purposes. Oxidative reaction plays major part of our life, cause production of reactive oxygen species. The aim of this study was to investigate the antioxidant activity of ethanol and ethyl acetate extract of two potential medicinal plants like Achyranthes aspera and Cassia auriculata. The crude extract of the plant was subjected to preliminary qualitative analysis to identify the major functional groups and phytochemical substances like alkaloids, flavonoids, phenolic compounds, carbohydrates, and proteins. Antioxidant activities of the plant extract was screened by free radical scavenging activity (DPPH). Dried leaf and stem powder of these medicinal plant was extracted and concentrated to yield a dry residue. Our findings indicate that Achyranthes aspera possess a significant antioxidant property followed by Cassia auriculata.

scholarly journals Oxidative Stress in Bacteria and the Central Dogma of Molecular Biology

2021 ◽  
Vol 8 ◽  
Author(s):  
Michel Fasnacht ◽  
Norbert Polacek
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Molecular Biology ◽  
Reactive Oxygen ◽  
Cellular Metabolism ◽  
Life Forms ◽  
Oxygen Species ◽  
Central Dogma ◽  
Great Oxidation Event ◽  
Cellular Life

Ever since the “great oxidation event,” Earth’s cellular life forms had to cope with the danger of reactive oxygen species (ROS) affecting the integrity of biomolecules and hampering cellular metabolism circuits. Consequently, increasing ROS levels in the biosphere represented growing stress levels and thus shaped the evolution of species. Whether the ROS were produced endogenously or exogenously, different systems evolved to remove the ROS and repair the damage they inflicted. If ROS outweigh the cell’s capacity to remove the threat, we speak of oxidative stress. The injuries through oxidative stress in cells are diverse. This article reviews the damage oxidative stress imposes on the different steps of the central dogma of molecular biology in bacteria, focusing in particular on the RNA machines involved in transcription and translation.

scholarly journals The Fumarate Reductase ofBacteroides thetaiotaomicron, unlike That ofEscherichia coli, Is Configured so that It Does Not Generate Reactive Oxygen Species

mBio ◽  
2017 ◽  
Vol 8 (1) ◽  
Author(s):  
Zheng Lu ◽  
James A. Imlay
Keyword(s):  
Reactive Oxygen Species ◽  
Reactive Oxygen ◽  
Fumarate Reductase ◽  
High Rate ◽  
Ros Generation ◽  
Oxygen Species ◽  
Redox Enzymes ◽  
Oxygen Oxygen ◽  
Related Enzyme ◽  
The Impact

ABSTRACTThe impact of oxidative stress upon organismal fitness is most apparent in the phenomenon of obligate anaerobiosis. The root cause may be multifaceted, but the intracellular generation of reactive oxygen species (ROS) likely plays a key role. ROS are formed when redox enzymes accidentally transfer electrons to oxygen rather than to their physiological substrates. In this study, we confirm that the predominant intestinal anaerobeBacteroides thetaiotaomicrongenerates intracellular ROS at a very high rate when it is aerated. Fumarate reductase (Frd) is a prominent enzyme in the anaerobic metabolism of many bacteria, includingB. thetaiotaomicron, and prior studies ofEscherichia coliFrd showed that the enzyme is unusually prone to ROS generation. Surprisingly, in this study biochemical analysis demonstrated that theB. thetaiotaomicronFrd does not react with oxygen at all: neither superoxide nor hydrogen peroxide is formed. Subunit-swapping experiments indicated that this difference does not derive from the flavoprotein subunit at which ROS normally arise. Experiments with the related enzyme succinate dehydrogenase discouraged the hypothesis that heme moieties are responsible. Thus, resistance to oxidation may reflect a shift of electron density away from the flavin moiety toward the iron-sulfur clusters. This study shows that the autoxidizability of a redox enzyme can be suppressed by subtle modifications that do not compromise its physiological function. One implication is that selective pressures might enhance the oxygen tolerance of an organism by manipulating the electronic properties of its redox enzymes so they do not generate ROS.IMPORTANCEWhether in sediments or pathogenic biofilms, the structures of microbial communities are configured around the sensitivities of their members to oxygen. Oxygen triggers the intracellular formation of reactive oxygen species (ROS), and the sensitivity of a microbe to oxygen likely depends upon the rates at which ROS are formed inside it. This study supports that idea, as an obligate anaerobe was confirmed to generate ROS very rapidly upon aeration. However, the suspected source of the ROS was disproven, as the fumarate reductase of the anaerobe did not display the high oxidation rate of itsE. colihomologue. Evidently, adjustments in its electronic structure can suppress the tendency of an enzyme to generate ROS. Importantly, this outcome suggests that evolutionary pressure may succeed in modifying redox enzymes and thereby diminishing the stress that an organism experiences in oxic environments. The actual source of ROS in the anaerobe remains to be discovered.

scholarly journals Bioenergetics adaptations and redox homeostasis in pregnancy and related disorders

2021 ◽  
Author(s):  
Lissette Sanchez-Aranguren ◽  
Sarah Nadeem
Keyword(s):  
Intrauterine Growth Restriction ◽  
Redox Homeostasis ◽  
Oxygen Species ◽  
Metabolic Intermediates ◽  
Intrauterine Growth ◽  
Metabolic Adaptations ◽  
Metabolic Fingerprint ◽  
Pathological Pregnancy ◽  
Molecular Aspects ◽  
Health Complications

AbstractPregnancy is a challenging physiological process that involves maternal adaptations to the increasing energetics demands imposed by the growing conceptus. Failure to adapt to these requirements may result in serious health complications for the mother and the baby. The mitochondria are biosynthetic and energy-producing organelles supporting the augmented energetic demands of pregnancy. Evidence suggests that placental mitochondria display a dynamic phenotype through gestation. At early stages of pregnancy placental mitochondria are mainly responsible for the generation of metabolic intermediates and reactive oxygen species (ROS), while at later stages of gestation, the placental mitochondria exhibit high rates of oxygen consumption. This review describes the metabolic fingerprint of the placental mitochondria at different stages of pregnancy and summarises key signs of mitochondrial dysfunction in pathological pregnancy conditions, including preeclampsia, gestational diabetes and intrauterine growth restriction (IUGR). So far, the effects of placental-driven metabolic changes governing the metabolic adaptations occurring in different maternal tissues in both, healthy and pathological pregnancies, remain to be uncovered. Understanding the function and molecular aspects of the adaptations occurring in placental and maternal tissue’s mitochondria will unveil potential targets for further therapeutic exploration that could address pregnancy-related disorders. Targeting mitochondrial metabolism is an emerging approach for regulating mitochondrial bioenergetics. This review will also describe the potential therapeutic use of compounds with a recognised effect on mitochondria, for the management of preeclampsia.

scholarly journals Light-induced catalytic and cytotoxic properties of phosphorescent transition metal compounds with a d 8 electronic configuration

2013 ◽  
Vol 371 (1995) ◽  
pp. 20120126 ◽  
Author(s):  
Wai-Pong To ◽  
Taotao Zou ◽  
Raymond Wai-Yin Sun ◽  
Chi-Ming Che
Keyword(s):  
Transition Metal ◽  
Excited States ◽  
Electronic Configuration ◽  
Transition Metal Compounds ◽  
Triplet States ◽  
Oxygen Species ◽  
Bimolecular Reactions ◽  
Metal Compounds ◽  
Light Emitting ◽  
Triplet Excited States

Transition metal compounds are well documented to have diverse applications such as in catalysis, light-emitting materials and therapeutics. In the areas of photocatalysis and photodynamic therapy, metal compounds of heavy transition metals are highly sought after because they can give rise to triplet excited states upon photoexcitation. The long lifetimes (more than 1 μs) of the triplet states of transition metal compounds allow for bimolecular reactions/processes such as energy transfer and/or electron transfer to occur. Reactions of triplet excited states of luminescent metal compounds with oxygen in cells may generate reactive oxygen species and/or induce damage to DNA, leading to cell death. This article recaps the recent findings on photochemical and phototoxic properties of luminescent platinum(II) and gold(III) compounds both from the literature and experimental results from our group.

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