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Glycolysis at 75: Is it time to tweak the first elucidated metabolic pathway in history?

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889195862 Year: Pages: 126 DOI: 10.3389/978-2-88919-586-2 Language: English
Publisher: Frontiers Media SA
Subject: Nutrition and Food Sciences --- Medicine (General) --- Neurology --- Science (General)
Added to DOAB on : 2016-03-10 08:14:32
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Glycolysis, the pathway of enzymatic reactions responsible for the breakdown of glucose into two trioses and further into pyruvate or lactate, was elucidated in 1940. For more than seven decades, it has been taught precisely the way its sequence was proposed by Embden, Meyerhof and Parnas. Accordingly, two outcomes of this pathway were proposed, an aerobic glycolysis, with pyruvate as its final product, and an anaerobic glycolysis, identical to the aerobic one, except for an additional reaction, where pyruvate is reduced to lactate. Several studies in the 1980s have shown that both muscle and brain tissues can oxidize and utilize lactate as an energy substrate, challenging this monocarboxylate’s reputation as a useless end-product of anaerobic glycolysis. These findings were met with great skepticism about the idea that lactate could be playing a role in bioenergetics. In the past quarter of a century monocarboxylate transporters (MCTs) were identified and localized in both cellular and mitochondrial membranes. A lactate receptor has been identified. Direct and indirect evidence now indicate that the enzyme lactate dehydrogenase (LDH) resides not only in the cytosol, as part of the glycolytic pathway machinery, but also in the mitochondrial outer membrane. The mitochondrial form of the enzyme oxidizes lactate to pyruvate and concomitantly produces the reducing agent NADH. These findings have shed light on a major drawback of the originally proposed aerobic version of the glycolytic pathway i.e., its inability to regenerate NAD+, as opposed to anaerobic glycolysis that features the cyclical ability of regenerating NAD+ upon pyruvate reduction to lactate by the cytosolic form of LDH. The malate-aspartate shuttle (MAS), a major redox shuttle in the brain, was proposed as an alternative pathway for NAD+ generation for aerobic glycolysis. Nonetheless, would MAS really be necessary for that function if glycolysis always proceeds to the end-products, lactate and NAD+? An additional dilemma the originally proposed aerobic glycolysis presents has to do with the glycolytic pathway of erythrocytes, which despite its highly aerobic environment, always produces lactate as its end-product. It is time to reexamine the original, dogmatic separation of glycolysis into two distinct pathways and put to test the hypothesis of a unified, singular pathway, the end-product of which is lactate, the real substrate of the mitochondrial TCA cycle.

The metabolic challenges of immune cells in health and disease

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889196227 Year: Pages: 80 DOI: 10.3389/978-2-88919-622-7 Language: English
Publisher: Frontiers Media SA
Subject: Allergy and Immunology --- Medicine (General)
Added to DOAB on : 2016-08-16 10:34:25
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Obesity and its co-morbidities, including atherosclerosis, insulin resistance and diabetes, are a world-wide epidemic. Inflammatory immune responses in metabolic tissues have emerged as a universal feature of these metabolic disorders. While initial work highlighted the contribution of macrophages to tissue inflammation and insulin resistance, recent studies demonstrate that cells of the adaptive immune compartment, including T and B lymphocytes and dendritic cells also participate in obesity-induced pathogenesis of these conditions. However, the molecular and cellular pathways by which the innate and adaptive branches of immunity control tissue and systemic metabolism remain poorly understood. To engage in growth and activation, cells need to increase their biomass and replicate their genome. This process presents a substantial bioenergetic challenge: growing and activated cells must increase ATP production and acquire or synthesize raw materials, including lipids, proteins and nucleic acids. To do so, they actively reprogram their intracellular metabolism from catabolic mitochondrial oxidative phosphorylation to glycolysis and other anabolic pathways. This metabolic reprogramming is under the control of specific signal transduction pathways whose underlying molecular mechanisms and relevance to physiology and disease are subject of considerable current interest and under intense study. Recent reports have elucidated the physiological role of metabolic reprogramming in macrophage and T cell activation and differentiation, B- and dendritic cell biology, as well as in the crosstalk of immune cells with endothelial and stem cells. It is also becoming increasingly evident that alterations of metabolic pathways play a major role in the pathogenesis of chronic inflammatory disorders. Due to the scientific distance between immunologists and experts in metabolism (e.g., clinicians and biochemists), however, there has been limited cross-talk between these communities. This collection of articles aims at promoting such cross-talk and accelerating discoveries in the emerging field of immunometabolism.

Cancer Metabolism: Molecular Targeting and Implications for Therapy

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889453221 Year: Pages: 114 DOI: 10.3389/978-2-88945-322-1 Language: English
Publisher: Frontiers Media SA
Subject: Medicine (General) --- Oncology
Added to DOAB on : 2018-02-27 16:16:45
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Development of an effective anticancer therapeutic necessitates the selection of cancer-related or cancer-specific pathways or molecules that are sensitive to intervention. Several such critical yet sensitive molecular targets have been recognized, and their specific antagonists or inhibitors validated as potential therapeutics in preclinical models. Yet, majority of anticancer principles or therapeutics show limited success in the clinical translation. Thus, the need for the development of an effective therapeutic strategy persists. “Altered energy metabolism” in cancer is one of the earliest known biochemical phenotypes which dates back to the early 20th century. The German scientist, Otto Warburg and his team (Warburg, Wind, Negelein 1926; Warburg, Wind, Negelein 1927) provided the first evidence that the glucose metabolism of cancer cells diverge from normal cells. This phenomenal discovery on deregulated glucose metabolism or cellular bioenergetics is frequently witnessed in majority of solid malignancies. Currently, the altered glucose metabolism is used in the clinical diagnosis of cancer through positron emission tomography (PET) imaging. Thus, the “deregulated bioenergetics” is a clinically relevant metabolic signature of cancer cells, hence recognized as one of the hallmarks of cancer (Hanahan and Weinberg 2011). Accumulating data unequivocally demonstrate that, besides cellular bioenergetics, cancer metabolism facilitates several cancer-related processes including metastasis, therapeutic resistance and so on. Recent reports also demonstrate the oncogenic regulation of glucose metabolism (e.g. glycolysis) indicating a functional link between neoplastic growth and cancer metabolism. Thus, cancer metabolism, which is already exploited in cancer diagnosis, remains an attractive target for therapeutic intervention as well. The Frontiers in Oncology Research Topic “Cancer Metabolism: Molecular Targeting and Implications for Therapy” emphases on recent advances in our understanding of metabolic reprogramming in cancer, and the recognition of key molecules for therapeutic targeting. Besides, the topic also deliberates the implications of metabolic targeting beyond the energy metabolism of cancer. The research topic integrates a series of reviews, mini-reviews and original research articles to share current perspectives on cancer metabolism, and to stimulate an open forum to discuss potential challenges and future directions of research necessary to develop effective anticancer strategies.

Cell Stress, Metabolic Reprogramming, and Cancer

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889455652 Year: Pages: 68 DOI: 10.3389/978-2-88945-565-2 Language: English
Publisher: Frontiers Media SA
Subject: Medicine (General) --- Oncology
Added to DOAB on : 2019-01-23 14:53:43
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The present eBook presents one review, five mini-reviews, and an opinion article on the achievements and perspectives of studies on important aspects of cancer cell metabolic reprogramming whose mechanisms and regulation are still largely elusive. It also sheds light on certain novel functional components, which rewires cell metabolism in tumor transformation.

Plant Proteomic Research 2.0

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ISBN: 9783039210626 / 9783039210633 Year: Pages: 594 DOI: 10.3390/books978-3-03921-063-3 Language: eng
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Science (General) --- Biology --- Plant Sciences
Added to DOAB on : 2019-06-26 08:44:07
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Advancements in high-throughput “Omics” techniques have revolutionized plant molecular biology research. Proteomics offers one of the best options for the functional analysis of translated regions of the genome, generating a wealth of detailed information regarding the intrinsic mechanisms of plant stress responses. Various proteomic approaches are being exploited extensively for elucidating master regulator proteins which play key roles in stress perception and signaling, and these approaches largely involve gel-based and gel-free techniques, including both label-based and label-free protein quantification. Furthermore, post-translational modifications, subcellular localization, and protein–protein interactions provide deeper insight into protein molecular function. Their diverse applications contribute to the revelation of new insights into plant molecular responses to various biotic and abiotic stressors.

Keywords

Phalaenopsis --- petal --- pollination --- senescence --- 2-DE --- ROS --- Medicago sativa --- leaf cell wall proteome --- cadmium --- quantitative proteomics --- 2D DIGE --- chloroplast --- elevated CO2 --- heat stress --- nucleotide pyrophosphatase/phosphodiesterase --- (phospho)-proteomics --- photosynthesis --- protein phosphorylation --- 14-3-3 proteins --- Oryza sativa L. --- starch --- sucrose --- N utilization efficiency --- proteomics --- 2D --- protein phosphatase --- rice isogenic line --- SnRK1 --- 14-3-3 --- lettuce --- bolting --- proteome --- high temperature --- iTRAQ --- proteome profiling --- iTRAQ --- differentially abundant proteins (DAPs) --- drought stress --- physiological responses --- Zea mays L. --- GS3 --- ? subunit --- heterotrimeric G protein --- mass spectrometric analysis --- RGG3 --- rice --- western blotting --- Dn1-1 --- ?-subunit --- heterotrimeric G protein --- mass spectrometry analysis --- RGG4 --- rice --- western blotting --- Clematis terniflora DC. --- polyphenol oxidase --- virus induced gene silencing --- photosynthesis --- glycolysis --- Camellia sinensis --- chlorotic mutation --- chlorophyll deficiency --- weakening of carbon metabolism --- iTRAQ --- proteomics --- degradome --- wheat --- cultivar --- protease --- papain-like cysteine protease (PLCP) --- subtilase --- metacaspase --- caspase-like --- wheat leaf rust --- Puccinia recondita --- Stagonospora nodorum --- iTRAQ --- proteomics --- somatic embryogenesis --- pyruvate biosynthesis --- Zea mays --- chlorophylls --- LC-MS-based proteomics --- pea (Pisum sativum L.) --- proteome functional annotation --- proteome map --- seeds --- seed proteomics --- late blight disease --- potato proteomics --- Phytophthora infestans --- Sarpo Mira --- early and late disease stages --- Simmondsia chinensis --- cold stress --- proteomics --- leaf --- iTRAQ --- Ricinus communis L. --- cold stress --- seed imbibition --- iTRAQ --- proteomics --- Morus --- organ --- gel-free/label-free proteomics --- flavonoid --- antioxidant activity --- phosphoproteome --- barley --- seed dormancy --- germination --- imbibition --- after-ripening --- sugarcane --- Sporisorium scitamineum --- smut --- proteomics --- RT-qPCR --- ISR --- holm oak --- Quercus ilex --- 2-DE proteomics --- shotgun proteomics --- non-orthodox seed --- population variability --- stresses responses --- ammonium --- Arabidopsis thaliana --- carbon metabolism --- nitrogen metabolism --- nitrate --- proteomics --- root --- secondary metabolism --- proteomics --- wheat --- silver nanoparticles --- plant pathogenesis responses --- data-independent acquisition --- quantitative proteomics --- Pseudomonas syringae --- sweet potato plants infected by SPFMV --- SPV2 and SPVG --- sweet potato plants non-infected by SPFMV --- SPV2 and SPVG --- co-infection --- transcriptome profiling --- gene ontology --- pathway analysis --- lesion mimic mutant --- leaf spot --- phenylpropanoid biosynthesis --- proteomics --- isobaric tags for relative and absolute quantitation (iTRAQ) --- rice --- affinity chromatography --- ergosterol --- fungal perception --- innate immunity --- pattern recognition receptors --- plasma membrane --- proteomics --- proteomics --- maize --- plant-derived smoke --- shoot --- Solanum tuberosum --- patatin --- seed storage proteins --- vegetative storage proteins --- tuber phosphoproteome --- targeted two-dimensional electrophoresis --- B. acuminata petals --- MALDI-TOF/TOF --- GC-TOF-MS --- qRT-PCR --- differential proteins --- n/a

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