Academic literature on the topic 'Krebs cycle metabolism'
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the lists of relevant articles, books, theses, conference reports, and other scholarly sources on the topic 'Krebs cycle metabolism.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Journal articles on the topic "Krebs cycle metabolism"
1
Lindsay, Angus, Christopher M. Chamberlain, Bruce A. Witthuhn, Dawn A. Lowe, and James M. Ervasti. "Dystrophinopathy-associated dysfunction of Krebs cycle metabolism." Human Molecular Genetics 28, no. 6 (November 21, 2018): 942–51. http://dx.doi.org/10.1093/hmg/ddy404.
Full text
2
Shimodahira, Makiko, Shimpei Fujimoto, Eri Mukai, Yasuhiko Nakamura, Yuichi Nishi, Mayumi Sasaki, Yuichi Sato, et al. "Rapamycin impairs metabolism-secretion coupling in rat pancreatic islets by suppressing carbohydrate metabolism." Journal of Endocrinology 204, no. 1 (October 7, 2009): 37–46. http://dx.doi.org/10.1677/joe-09-0216.
Full textAbstract:
Rapamycin, an immunosuppressant used in human transplantation, impairs β-cell function, but the mechanism is unclear. Chronic (24 h) exposure to rapamycin concentration dependently suppressed 16.7 mM glucose-induced insulin release from islets (1.65±0.06, 30 nM rapamycin versus 2.35±0.11 ng/islet per 30 min, control, n=30, P<0.01) without affecting insulin and DNA contents. Rapamycin also decreased α-ketoisocaproate-induced insulin release, suggesting reduced mitochondrial carbohydrate metabolism. ATP content in the presence of 16.7 mM glucose was significantly reduced in rapamycin-treated islets (13.42±0.47, rapamycin versus 16.04±0.46 pmol/islet, control, n=30, P<0.01). Glucose oxidation, which indicates the velocity of metabolism in the Krebs cycle, was decreased by rapamycin in the presence of 16.7 mM glucose (30.1±2.7, rapamycin versus 42.2±3.3 pmol/islet per 90 min, control, n=9, P<0.01). Immunoblotting revealed that the expression of complex I, III, IV, and V was not affected by rapamycin. Mitochondrial ATP production indicated that the respiratory chain downstream of complex II was not affected, but that carbohydrate metabolism in the Krebs cycle was reduced by rapamycin. Analysis of enzymes in the Krebs cycle revealed that activity of α-ketoglutarate dehydrogenase (KGDH), which catalyzes one of the slowest reactions in the Krebs cycle, was reduced by rapamycin (10.08±0.82, rapamycin versus 13.82±0.84 nmol/mg mitochondrial protein per min, control, n=5, P<0.01). Considered together, these findings indicate that rapamycin suppresses high glucose-induced insulin secretion from pancreatic islets by reducing mitochondrial ATP production through suppression of carbohydrate metabolism in the Krebs cycle, together with reduced KGDH activity.
3
Magnusson, I., W. C. Schumann, G. E. Bartsch, V. Chandramouli, K. Kumaran, J. Wahren, and B. R. Landau. "Noninvasive tracing of Krebs cycle metabolism in liver." Journal of Biological Chemistry 266, no. 11 (April 1991): 6975–84. http://dx.doi.org/10.1016/s0021-9258(20)89598-2.
Full text
4
Ritson, Dougal J. "A cyanosulfidic origin of the Krebs cycle." Science Advances 7, no. 33 (August 2021): eabh3981. http://dx.doi.org/10.1126/sciadv.abh3981.
Full textAbstract:
The centrality of the Krebs cycle in metabolism has long been interpreted as evidence of its antiquity, and consequently, questions regarding its provenance, and whether it initially functioned as a cycle or not, have received much attention. The present report shows that prebiotic oxidation of α-hydroxy carboxylates can be achieved by UV photolysis of a simple geochemical species (HS−), which leads to α-oxo carboxylates that feature in the Krebs cycle and glyoxylate shunt. Further reaction of these products leads to almost all intermediates of the Krebs cycle proper, succinate semialdehyde bypass, and glyoxylate shunt. Fumarate, the missing Krebs cycle component, and the required α-hydroxy carboxylates can be provided by a highly related hydrogen cyanide chemistry, which also provides precursors for amino acids, nucleotides, and phospholipids.
5
Radzikh, Igor, Erica Fatica, Jillian Kodger, Rohan Shah, Ryan Pearce, and Yana I. Sandlers. "Metabolic Outcomes of Anaplerotic Dodecanedioic Acid Supplementation in Very Long Chain Acyl-CoA Dehydrogenase (VLCAD) Deficient Fibroblasts." Metabolites 11, no. 8 (August 13, 2021): 538. http://dx.doi.org/10.3390/metabo11080538.
Full textAbstract:
Very long-chain acyl-CoA dehydrogenase deficiency (VLCADD, OMIM 609575) is associated with energy deficiency and mitochondrial dysfunction and may lead to rhabdomyolysis and cardiomyopathy. Under physiological conditions, there is a fine balance between the utilization of different carbon nutrients to maintain the Krebs cycle. The maintenance of steady pools of Krebs cycle intermediates is critical formitochondrial energy homeostasis especially in high-energy demanding organs such as muscle and heart. Even-chain dicarboxylic acids are established as alternative energy carbon sources that replenish the Krebs cycle by bypassing a defective β-oxidation pathway. Despite this, even-chain dicarboxylic acids are eliminated in the urine of VLCAD-affected individuals. In this study, we explore dodecanedioic acid (C12; DODA) supplementation and investigate its metabolic effect on Krebs cycle intermediates, glucose uptake, and acylcarnitine profiles in VLCAD-deficient fibroblasts. Our findings indicate that DODA supplementation replenishes the Krebs cycle by increasing the succinate pool, attenuates glycolytic flux, and reduces levels of toxic very long-chain acylcarnitines.
6
He, Miao, Mulan Chen, Mingxue Liu, Faqin Dong, Hongfu Wei, and Danni Wang. "Effects and mechanism of riboflavin on the growth of Alcaligenes faecalis under bias conditions." RSC Advances 9, no. 40 (2019): 22957–65. http://dx.doi.org/10.1039/c9ra04066h.
Full text
7
Costa, C., and E. Galembeck. "THE EVOLUTION OF THE KREBS CYCLE: A PROMISING THEME FOR MEANINGFUL BIOCHEMISTRY LEARNING IN BIOLOGY." Revista de Ensino de Bioquímica 13 (August 24, 2015): 9. http://dx.doi.org/10.16923/reb.v13i2.577.
Full textAbstract:
INTRODUCTION: Evolution has been recognized as a key concept for biologists. In order to motivate biology undergraduates for contents of central energetic metabolism, we addressed the Krebs cycle structure and functions to an evolutionary view. To this end, we created a study guide which contextualizes the emergence of the cyclic pathway, in light of the prokaryotic influence since early Earth anaerobic condition to oxygen rise in atmosphere. OBJECTIVES: The main goal is to highlight the educational potential of the material whose subject is scarcely covered in biochemistry textbooks. MATERIALS AND METHODS: The study guide is composed by three interrelated sections, the problem (Section 1), designed to arouse curiosity, inform and motivate students; an introductory text (Section 2) about life evolution, including early micro-organisms and Krebs cycle emergence, and questions (Section 3) for debate. The activity consisted on a peer discussion session, with instructors tutoring. The questions were designed to foster exchange of ideas in an ever-increasing level of complexity, and cover subjects from early atmospheric conditions to organization of the metabolism along the subsequent geological ages. RESULTS AND DISCUSSION: We noticed that students were engaged and motivated by the task, especially during group discussion. Based on students’ feedbacks and class observations, we learned that the material raised curiosity and stimulated discussion among peers. It brought a historical and purposeful way of dealing with difficult biochemical concepts. CONCLUSIONS: The whole experience suggests that the study guide was a stimulus for broadening comprehension of the Krebs cycle, reinforcing the evolutionary stance as an important theme for biology and biochemistry understanding. On the other hand, we do not underestimate the fact that approaching Krebs cycle from an evolutionary standpoint is a quite complex discussion for the majority of students. KEYWORDS: Evolution. Krebs cycle. Metabolism learning. Biology. ACKNOWLEDGEMENTS: We thank Capes for financial support.
8
Landau, B. R., W. C. Schumann, V. Chandramouli, I. Magnusson, K. Kumaran, and J. Wahren. "14C-labeled propionate metabolism in vivo and estimates of hepatic gluconeogenesis relative to Krebs cycle flux." American Journal of Physiology-Endocrinology and Metabolism 265, no. 4 (October 1, 1993): E636—E647. http://dx.doi.org/10.1152/ajpendo.1993.265.4.e636.
Full textAbstract:
Purposes of this study were 1) to estimate in humans, using 14C-labeled propionate, the rate of hepatic gluconeogenesis relative to the rate of Krebs cycle flux; 2) to compare those rates with estimates previously made using [3-14C]lactate and [2-14C]acetate; 3) to determine if the amount of ATP required for that rate of gluconeogenesis could be generated in liver, calculated from that rate of Krebs cycle flux and splanchnic balance measurements, previously made, and 4) to test whether hepatic succinyl-CoA is channeled during its metabolism through the Krebs cycle. [2-14C]propionate, [3-14C]-propionate, and [2,3-14C]succinate were given along with phenyl acetate to normal subjects, fasted 60 h. Distributions of 14C were determined in the carbons of blood glucose and of glutamate from excreted phenylacetylglutamine. Corrections to the distributions for 14CO2 fixation were made from the specific activities of urinary urea and the specific activities in glucose, glutamate, and urea previously found on administering [14C]-bicarbonate. Uncertainties in the corrections and in the contributions of pyruvate and Cori cyclings limit the quantitations. The rate of gluconeogenesis appears to be two or more times the rate of Krebs cycle flux and pyruvate's decarboxylation to acetyl-CoA, metabolized in the cycle, less than one-twenty-fifth the rate of its decarboxylation. Such estimates were previously made using [3-14C]lactate. The findings support the use of phenyl acetate to sample hepatic alpha-ketoglutarate. Ratios of specific activities of glucose to glutamate and glucose to urinary urea and expired CO2 indicate succinate's extensive metabolism when presented in trace amounts to liver. Utilizations of the labeled compounds by liver relative to other tissues were in the order succinate = lactate > propionate > acetate. ATP required for gluconeogenesis and urea formation was approximately 40% of the amount of ATP generated in liver. There was no channeling of succinyl-CoA in the Krebs cycle in the hepatic mitochondria.
9
Thies, R. S., and L. J. Mandel. "Role of glucose in corneal metabolism." American Journal of Physiology-Cell Physiology 249, no. 5 (November 1, 1985): C409—C416. http://dx.doi.org/10.1152/ajpcell.1985.249.5.c409.
Full textAbstract:
Glucose catabolism by glycolysis and the Krebs cycle was examined in the isolated rabbit cornea incubated with [6-14C]glucose. The production of [14C]lactate and 14CO2 from this substrate provided minimal values for the fluxes through these pathways since the tissue was in metabolic steady state but not isotopic steady state during the 40-min incubation. The specific activity of lactate under these conditions was one-third of that for [6-14C]glucose, and label dilution by exchange with unlabeled alanine was minimal, suggesting that glycogen degradation was primarily responsible for this dilution of label in the Embden-Meyerhof pathway. In addition, considerable label accumulation was found in glutamate and aspartate. Calculations revealed that these endogenous amino acid pools were not isotopically equilibrated after the incubation period, suggesting that they were responsible for the isotopic nonsteady state by exchange dilution through transaminase reactions with labeled intermediates. An estimate of glucose oxidation by the Krebs cycle, which was corrected for label dilution by exchange, indicated that glucose could account for most of the measured corneal oxygen consumption that was coupled to oxidative phosphorylation. A minor component of this respiration could not be accounted for by glucose or glycogen oxidation. Additional experiments suggested that endogenous fatty acid oxidation was probably also active under these conditions. Finally, reciprocal changes in plasma membrane Na+-K+-ATPase activity induced by ouabain and nystatin were found to concomitantly alter oxygen consumption rates and [14C]lactate production from [6-14C]glucose. These results demonstrated the capacity for regulating glycolysis and the Krebs cycle in response to changing energy demands in the cornea.
10
De C. Fonseca, M., C. J. Aguiar, J. A. Da Rocha Franco, R. N. Gingold, and M. F. Leite. "GPR91: EXPANDING THE FRONTIERS OF KREBS CYCLE INTERMEDIATES." Nephrology (Saint-Petersburg) 21, no. 1 (March 3, 2017): 9–18. http://dx.doi.org/10.24884/1561-6274-2017-21-1-9-18.
Full textAbstract:
Since it was discovered, the citric acid cycle has been known to be central to cell metabolism and energy homeostasis. Mainly found in the mitochondrial matrix, some of the intermediates of the Krebs cycle are also present in the blood stream. Currently, there are several reports that indicate functional roles for Krebs intermediates out of its cycle. Succinate, for instance, acts as an extracellular ligand by binding to a G-protein coupled receptor, known as GPR91, expressed in kidney, liver, heart, retinal cells and possibly many other tissues. Succinate activated GPR91 induces a wide array of physiological and pathological effects. Through GPR91, succinate is involved in functions such as regulation of blood pressure, inhibition of lipolysis in white adipose tissue, development of retinal vascularization, cardiac hypertrophy and activation of stellate hepatic cells by ischemic hepatocytes. Current review is dedicated to discussion of these effects.
Dissertations / Theses on the topic "Krebs cycle metabolism"
1
Varma, Sreejith Jayasree. "Mimicking C-C bond forming reactions of core metabolism." Thesis, Strasbourg, 2018. http://www.theses.fr/2018STRAF038/document.
Full textAbstract:
Toutes les formes de vie assemblent et désassemblent continuellement des composés chimiques via un processus de consommation d'énergie appelé métabolisme. Le métabolisme est généralement modélisé en chimie et biologie par un cycle. Ce modèle dynamique traduit la transformation de composés de base en une cascade de produits appelés métabolites. Celui-ci est comparable à un ouragan à l’échelle moléculaire. De manière analogique et imagée un cyclone est constitué de deux éléments, l'air et l'eau, et transforme l’environnement qui l’entoure par un processus endothermique (consommateur d’énergie). Traditionnellement, la recherche chimique sur les origines de la vie est concentrée principalement sur la synthèse de composés chimiques sans suffisamment apprécier leur place dans la plus grande organisation biochimique de la vie. La vie construit toutes ses molécules à partir du dioxyde de carbone, pourtant elle manque étonnamment d'innovation à cet égard. Malgré presque 4 milliards d'années d'évolution, les organismes autotrophes utilisent seulement six voies différentes pour construire leurs molécules à partir du CO2. Parmi elles, deux voies – la voie de l’acétyle CoA (aussi appelée voie Wood-Ljungdahl) et le cycle du rTCA (également appelé le cycle de Krebs inverse) - sont considérées comme primitives, et contiennent les cinq molécules servant de précurseurs chimiques universels pour toute la biochimie. Comment et pourquoi les voies de l’acétyle CoA et du rTCA sont-elles apparues? Pour répondre à cette question, une recherche systématique a été effectuée afin de trouver des catalyseurs chimiques non-enzymatiques ou des minéraux simples, ainsi que des réactifs pouvant promouvoir les réactions d'anabolisme principal, particulièrement la voie de l’Acétyle CoA et le cycle de rTCA. A l’origine, pour créer les molécules organiques complexes comme les enzymes il a fallu que des molécules plus simples avec un moins grand nombre de carbone se forme sur terre et cela à partir du CO2. On peut donc supposer que les premiers produits à plusieurs carbones sont issus de synthèse totalement inorganique comme celles développer dans notre laboratoire, plutôt que d’une évolution chimique et organométallique simultanée, c’est-à-dire une interaction efficace entre une molécule carbonée et un ou plusieurs métaux à l’instar de certains enzymes. Après avoir trouvé autant de façons possible de promouvoir individuellement chaque étapes des cycles catalytiques étudiés, seules les conditions réactionnelles mutuellement compatibles (à savoir des conditions permettant de produire l’ensemble des métabolites dans le bon ordre) ont été retenuAll life forms continuously build up and break down its constituent chemical building blocks, through an energy consuming process called metabolism. Just like a hurricane’s dynamic patterns and its building blocks (air and water) as being equally fundamental to its nature, so too should metabolism’s dynamic chemical patterns and chemical building blocks be viewed as equally characteristic. Traditionally, much chemical research on the origins of life is overly focused on the synthesis of chemical building blocks without sufficiently appreciating their place in life’s larger biochemical self-organization. Life ultimately builds all of its molecules from carbon dioxide, yet it is surprisingly lacking in innovation in this respect. Despite nearly 4 billion years of evolution, autotrophic organisms use only six pathways to build their molecules from CO2. Two of these pathways – the acetyl CoA pathway (also known as the Wood-Ljungdahl pathway) and rTCA cycle (also known as the reverse Krebs cycle) - are thought to be ancestral, with just five molecules within them serving as the universal chemical precursors for all of biochemistry. How and why did these pathways get their start? To answer this question, a systematic search was designed to find simple, non-enzymatic chemical or mineral catalysts and reagents, that can promote the reactions of core anabolism, particularly the acetyl CoA pathway and the rTCA cycle. After finding as many ways as possible to promote each reaction, they could be narrowed down to mutually compatible conditions where many reactions can occur in sequence. The more of core anabolism that can be achieved under a single set of purely chemical conditions, the more likely it is to have constituted early prebiotic chemistry rather than a later product of chemical and biological evolution
2
Meek, David J. J. "Molecular and genetic characterization of putative TCA cycle operons on Sinorhizobium meliloti." Thesis, McGill University, 2001. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=33808.
Full textAbstract:
Genetic mapping of pDS15 revealed that this cosmid clone carries the Sinorhizobium meliloti TCA cycle genes mdh, sucCDAB, sdhAB and part of lpdA. Three genes (mdh, sucC , and sucA) were completely sequenced and submitted to GenBank. The nucleotide and amino acid sequences of the TCA cycle genes encoded on pDS15 were aligned and found to be highly homologous with other closely related rhizobial species. S. meliloti cells grown in LBmc express the mdh-sucCDAB operon as one transcript, based on RT-PCR results. Alternative sigma factor sigma54 was not found to have a role in mdh-sucCDAB expression. Despite considerable effort, we have not been able to isolate sucA mutants via random transposon Tn5tac1 mutagenesis to date. Homologous recombination between a plasmid-borne sucA::Tn5 and wild-type S. meliloti sucA failed to generate a bona fide mutant, as revealed by Southern blot analysis. Plasmid pDS15 was mutagenized with transposons Tn5, Tn5tac1, and Tn5-B20. Three Tn5-B20 insertions were mapped to mdh, sucD, and sucA respectively, and preliminary gene expression studies were done.
3
Wagner, Tristan. "Structural insights into mycobacterial central carbon metabolism : the catalytic mechanisms and regulatory properties of α-ketoglutarate decarboxylase (KGD)." Paris 6, 2011. http://www.theses.fr/2011PA066421.
Full textAbstract:
Le nœud métabolique au croisement du cycle de Krebs et de l’assimilation de l’azote est régi par l’α-kétoglutarate déshydrogénase (KDH), un complexe constitué des composants E1o, E2o et E3. Chez les actinobactéries le composant E2o n’existe pas, son domaine catalytique est fusionné à E1o (α-kétoglutarate décarboxylase : KGD). La liaison de KGD au complexe de la pyruvate déshydrogénase assure l’activité KDH dont la régulation est cruciale pour coordonner le flux de carbone. Les corynebactéries ont développé un système de contrôle unique par GarA, une protéine à domaine en tête de fourche (ce domaine appelé FHA reconnait les thréonines phosphorylées) régulé par phosphorylation. GarA coordonne la synthèse du glutamate en bloquant KGD via une reconnaissance ne passant pas par une phospho-thréonine. Le but de cette thèse est de comprendre au niveau moléculaire comment GarA inhibe KGD. Nous avons résolu la première structure d’un composant E1o avec son cofacteur. L’analyse de la catalyse de KGD montre d’importants changements conformationnels passant par la translocation d’une hélice externe (αE). GarA s’ancre à un site allostérique grâce à la reconnaissance d’un aspartate mimant la charge phosphate contenu sur l’hélice αE, sa fixation bloquera l’événement de translocation de l’hélice. L’inhibition est accentuée par un effet synergique avec le domaine E2o qui verrouille la position de l’hélice αE. Néanmoins ce phénomène peut être contrecarré par l’action d’un nouveau type d’activateur propre à KGD : l’acétyl-CoA. Sa fixation sur un autre site allostérique aidera la translocation de l’hélice αE en déplaçant des résidus impliqués dans le changement conformationnel
4
Azevedo, Ana Maria Ponzio de. "Nova tecnologia aplicada ao ensino de bioquímica : construção e validação de um software educacional do tipo jogo." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2005. http://hdl.handle.net/10183/14664.
Full textAbstract:
Este trabalho descreve o planejamento, desenvolvimento e validação de um modelo de software educacional. O aplicativo é um ambiente multimídia de ensino e aprendizagem do Metabolismo dos Glicídios e o Ciclo de Krebs, denominado e-Metabolismo: Glicídios e contém um jogo de seqüência para o ensino de Bioquímica, denominado Diagrama Metabólico Dinâmico Virtual. O estudo de teorias pedagógicas e a experiência em aulas com os alunos do curso de medicina da Fundação Faculdade Federal de Ciências Médicas de Porto Alegre apontou a necessidade de mudanças no ensino de Bioquímica com uso das novas tecnologias de informação e comunicação. A justificativa do uso de um jogo virtual como método de ensino tem por base os resultados obtidos com o uso de um jogo de seqüência lógica em tabuleiro, na Disciplina de Bioquímica. O desenvolvimento do e-Metabolismo: Glicídios, tendo como referência a prática pedagógica baseada na epistemologia genética Jean Piaget, incluiu no seu planejamento a escolha de ferramenta de programação para permitir a interação do usuário (aluno) com o ambiente. O produto utiliza amplamente recursos de multimídia e pode ser disponibilizado num servidor ou em forma de CD-ROM. O ambiente virtual possibilita a interação do aluno com o ambiente e com colegas e professores através de ferramentas como, por exemplo, acesso a e-mails, chats, fóruns, mapas conceituais e diário de bordo. Instrumentos de avaliação de software foram estudados e aplicados com alunos de Disciplinas de Bioquímica no sentido de validar o software e-Metabolismo tanto no que se refere aos aspectos técnicos como a aprendizagem do conteúdo pelos alunos. Experiências com o uso do software foram, primeiramente, realizadas com alunos do curso de Medicina da FFFCMPA e depois com alunos de outros cursos. O primeiro grupo de alunos que avaliaram o e-Metabolismo foi formado pelos monitores da Disciplina. Mapas conceituais, testes escritos e avaliação dos registros deixados pelos usuários no próprio software foram utilizados como instrumentos de avaliação do conhecimento dos alunos. O grau de satisfação com o uso do método de estudo, foi avaliado por um questionário, cujas respostas foram analisadas e categorizadas. Os resultados obtidos indicam que o ambiente apresenta interface de fácil acesso, desperta o interesse, possibilita ao aluno escolher de que maneira quer fazer o seu estudo sem prejuízos no seu desempenho e facilita o estudo, sendo, portanto, considerado válido como instrumento educacional. Por se tratar de um ambiente dinâmico, deve ser constantemente atualizado, e a versão atual contém as modificações sugeridas por professores e alunos, facilitando o uso na Internet e o acompanhamento do aluno.This work describes the planing, the development and the validation of a game-like educational software. This multimedia ambient was designed for the study of carbohydrates metabolic pathways and the Krebs's Cycle, called e-Metabolism: carbohydrates, and contains the sequential game, called Virtual Dynamic Metabolic Diagram. The study of pedagogical theories and experiments in classroom with medicine students of the “Fundação Faculdade Federal de Ciências Médicas de Porto Alegre”, pointed the necessity of changes in Biochemistry courses, involving new technologies of information and communication. The use of a game-like software as a tool for teaching is based on experiments related to the use of tray games at Biochemistry courses. The development of the e-Metabolism took as a reference the integrationists’ pedagogical practice, based on Jean Piaget's concepts, related to genetic epistemology and constructivism, yet allowing the professors to choose the teaching method they wish to use. This product integrates multimedia resources extensively, and can be used in computer networks or in the format of a CD-ROM. In the virtual environment students will be able to interact with the environment as well as with classmates and professors through such tools as chats, forums, concept maps and notepads. Software ’s evaluation Instruments were studied and applied with undergraduate students of Biochemistry classes in the way to value the eMetabolism software in its technical aspects and student’s content learning aspects. Conceptual maps, written tests and evaluation of user’s registers realized with this software where used as evaluation instruments of students knowledge. The level of satisfaction was evaluated by a questionnaire, which answers had been analyzed and categorized. The results show that the e-Metabolism is easy to use, awakes the interest and facilitates the study, improving the student performance and can be considered a valid educational instrument. Since this is a dynamic ambient and is constantly actualized, the current version contains the changes suggested by teachers and students, making easier to use it at the Internet and to do a better analysis of the student’s learning.
5
Najac, Chloé. "Spectroscopie RMN du 1H pondérée en diffusion, du 13C et du 17O : développements méthodologiques pour l’étude de la structure et de la fonction cellulaire in vivo." Thesis, Paris 11, 2014. http://www.theses.fr/2014PA112242/document.
Full textAbstract:
La spectroscopie par résonance magnétique nucléaire (RMN) est un outil puissant permettant d’acquérir des profils biochimiques du cerveau et de quantifier de nombreux paramètres cellulaires in vivo. Au cours de ce travail de thèse, nous nous sommes intéressés à trois techniques : (i) la spectroscopie RMN du 1H pondérée en diffusion, (ii) la spectroscopie RMN du carbone-13 (13C) et (iii) de l’oxygène-17 (17O) pour étudier la microstructure et la fonction cellulaire in vivo.Les métabolites cérébraux sont des traceurs endogènes spécifiques d’un type cellulaire (neurones et astrocytes) dont la diffusion dépend des nombreuses propriétés cellulaires (par exemple la viscosité du cytosol et la restriction intracellulaire). L’étude de la dépendance du coefficient de diffusion (ADC) aux temps de diffusion (td) permet de quantifier chacun de ces paramètres. En particulier, la mesure de l’ADC aux td longs permet d’évaluer la compartimentation des métabolites. Dans une première étude, nous avons mesuré l’ADC de plusieurs métabolites neuronaux et astrocytaires sur une large gamme de td (de ~80 ms à ~1 s) dans un large voxel dans le cerveau du macaque. Aucune dépendance de l’ADC de l’ensemble des métabolites au td n’a été observée suggérant que les métabolites diffusent majoritairement dans les prolongements neuronaux (axones, dendrites) et astrocytaires et ne sont pas confinés dans le corps cellulaire ou les organelles (mitochondries, noyau). La grande taille du voxel, liée à la sensibilité de détection limitée, ne nous a pas permis d’étudier la compartimentation des métabolites dans la substance blanche (SB) et la substance grise (SG). C’est pourquoi, une nouvelle étude a été réalisée dans le cerveau de l’Homme. Les résultats montrent que les métabolites diffusent dans des structures fibrillaires dans la SG et la SB. Enfin, une dernière étude, avec une gamme de td jusqu’à 2 s chez le macaque, nous a permis d’estimer, à l’aide de modèles analytiques simples mimant la structure cellulaire, la longueur des fibres neuronales (~110 μm) et astrocytaires (~70 μm). L’oxydation du glucose au sein des mitochondries permet de produire l’ATP (adénosine triphosphate), la principale source d’énergie de l’organisme. La spectroscopie du 13C permet de mesurer la vitesse de dégradation du glucose dans le cycle de Krebs (VTCA). Cette méthode est largement reconnue pour l’étude du métabolisme. Néanmoins, de nombreuses limitations, en termes de modélisation des données en détection indirecte ou de puissance émise dans le contexte du découplage hétéronucléaire en détection directe, ont été rencontrées sur notre scanner IRM. C’est pourquoi, la spectroscopie du 17O a ensuite été développée afin de quantifier la vitesse de consommation de l’oxygène pendant la phosphorylation oxydative (CMRO2). Des développements méthodologiques et technologiques ont été nécessaires et sont encore en cours pour mettre en place et valider cette technique qui n’a encore jamais été utilisée chez le macaqueMagnetic Resonance Spectroscopy is a unique tool that allows acquiring brain biochemical profiles and quantifying many cellular parameters in vivo. During this thesis, three different techniques have been developed: (i) 1H diffusion-weighted, (ii) carbone-13 (13C) and (iii) oxygen-17 (17O) NMR spectroscopy to study brain structure and function in vivo. Brain metabolites are cell-specific endogeneous tracers of the intracellular space whose translational diffusion depends on many cellular properties (e.g.: cytosol vicosity and intracellular restriction). Studying the variation of the diffusion coefficient (ADC) as a function of diffusion time (td) allows untangling and quantifying those parameters. In particular, measuring metabolites ADC at long diffusion times gives information about the metabolites compartmentation in cells. In a first study, we measured neuronal and astrocytic metabolites ADC over a large time window (from ~80 ms to ~1 s) in a large voxel in the macaque brain. No dependence of all metabolites ADC on td was observed suggesting that metabolites primarily diffuse in neuronal (dendrites and axons) and astrocytic processes and are not confined inside the cell body and organelles (nucleus, mitochondria). The large size of the voxel, due to low detection sensitivity, did not allow us to study metabolites compartmentation in pure white (WM) and grey matters (GM). Therefore, we performed a new study in the human brain. Results showed that in both WM and GM metabolites diffuse in fiber-like cell structure. Finally, using an even larger time window (up to 2 s) in the macaque brain and analytical models mimicking the cell structure, we estimated the length of neuronal (~110 μm) and astrocytic (~70 μm) processes. ATP (adenosine triphosphate), the main source of energy in the organism, is produced thanks to glucose oxidation inside the mitochondria. 13C NMR spectroscopy is a well-known technique to study brain energy metabolism and can be used to estimate the rate of glucose degradation within the Krebs cycle (VTCA). However, many limitations, concerning data modeling when performing indirect detection or power deposition due to heteronuclear decoupling during direct detection, were encountered on our MRI scanner. Therefore, 17O NMR spectroscopy was developed to quantify the rate of oxygen consumption during oxidative phosphorylation (CMRO2). Methodological and technological developments were necessary and are still ongoing to validate this technique, which has never been used with macaque
6
Viberg, Victor. "Quantifying metabolic fluxes using mathematical modeling." Thesis, Linköpings universitet, Institutionen för medicinsk teknik, 2018. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-149588.
Full textAbstract:
Background Cancer is one of the leading causes of death in Sweden. In order to develop better treatments against cancer we need to better understand it. One area of special interest is cancer metabolism and the metabolic fluxes. As these fluxes cannot be directly measured, modeling is required to determine them. Due to the complexity of cell metabolism, some limitations in the metabolism model are required. As the TCA-cycle (TriCarboxylic Acid cycle) is one of the most important parts of cell metabolism, it was chosen as a starting point. The primary goal of this project has been to evaluate the previously constructed TCA-cycle model. The first step of the evaluation was to determine the CI (Confidence Interval) of the model parameters, to determine the parameters’ identifiability. The second step was to validate the model to see if the model could predict data for which the model had not been trained for. The last step of the evaluation was to determine the uncertainty of the model simulation. Method The TCA-cycle model was created using Isotopicaly labeled data and EMUs (ElementaryMetabolic Units) in OpenFlux, an open source toolbox. The CIs of the TCA-cycle model parameters were determined using both OpenFlux’s inbuilt functionality for it as well as using amethod called PL (Profile Likelihood). The model validation was done using a leave one out method. In conjunction with using the leave on out method, a method called PPL (Prediction Profile Likelihood) was used to determine the CIs of the TCA-cycle model simulation. Results and Discussion Using PL to determine CIs had mixed success. The failures of PL are most likely caused by poor choice of settings. However, in the cases in which PL succeeded it gave comparable results to those of OpenFLux. However, the settings in OpenFlux are important, and the wrong settings can severely underestimate the confidence intervals. The confidence intervals from OpenFlux suggests that approximately 30% of the model parameters are identifiable. Results from the validation says that the model is able to predict certain parts of the data for which it has not been trained. The results from the PPL yields a small confidence interval of the simulation. These two results regarding the model simulation suggests that even though the identifiability of the parameters could be better, that the model structure as a whole is sound. Conclusion The majority of the model parameters in the TCA-cycle model are not identifiable, which is something future studies needs to address. However, the model is able to to predict data for which it has not been trained and the model has low simulation uncertainty.
7
Hamel, David. "Rôle du GPR91 dans la réponse à l'hypoxie-ischémie et l'importance de sa localisation intracellulaire." Thèse, 2013. http://hdl.handle.net/1866/12627.
Full textAbstract:
L'adaptation à l'environnement est essentielle à la survie cellulaire et des organismes en général. La capacité d'adaptation aux variations en oxygène repose sur des mécanismes de détection de l'hypoxie et une capacité à répondre en amorçant un programme d'angiogenèse. Bien que la contribution du facteur induit par l'hypoxie (HIF) est bien définie dans l'induction d'une telle réponse, d'autres mécanismes sont susceptibles d'être impliqués. Dans cette optique, les études démontrant l'influence du métabolisme énergétique sur le développement vasculaire sont de plus en plus nombreuses. L'un de ces composés, le succinate, a récemment été démontré comme étant le ligand du GPR91, un récepteur couplé aux protéines G. Parmi les différents rôles attribués à ce récepteur, notre laboratoire s'intéressa aux rôles du GPR91 dans la revascularisation observée suite à des situations d'hypoxie dont ceux affectant la rétine. Il existe cependant d'autres conditions pour lesquelles une revascularisation serait bénéfique notamment suite à un stress hypoxique-ischémique cérébral. Nos travaux ont pour objectifs de mieux comprendre le rôle et le fonctionnement de ce récepteur durant le développement et dans le cadre de pathologies affectant la formation de vaisseaux sanguins.
Dans un premier temps, nous avons déterminé le rôle du GPR91 dans la guérison suite à un stress hypoxique-ischémique cérébral chez le nouveau-né. Nous montrons que ce récepteur est exprimé dans le cerveau et en utilisant des souris n'exprimant pas le GPR91, nous démontrons que dans un modèle d'hypoxie-ischémie cérébrale néonatal l'angiogenèse prenant place au cours de la phase de guérison dépend largement du récepteur. L'injection intracérébrale de succinate induit également l'expression de nombreux facteurs proangiogéniques et les résultats suggèrent que le GPR91 contrôle la production de ces facteurs. De plus, l'injection de ce métabolite avant le modèle d'hypoxie-ischémie réduit substantiellement la taille de l'infarctus. In vitro, des essaies de transcription génique démontrent qu'à la fois les neurones et les astrocytes répondent au succinate en induisant l'expression de facteurs bénéfiques à la revascularisation.
En considérant le rôle physiologique important du GPR91, une seconde étude a été entreprise afin de comprendre les déterminants moléculaires régissant son activité. Bien que la localisation subcellulaire des RCPG ait traditionnellement été considérée comme étant la membrane plasmique, un nombre de publications indique la présence de ces récepteurs à l'intérieur de la cellule. En effet, tel qu'observé par microscopie confocale, le récepteur colocalise avec plusieurs marqueurs du réticulum endoplasmique, que celui-ci soit exprimé de façon endogène ou transfecté transitoirement. De plus, l’activation des gènes par stimulation avec le succinate est fortement affectée en présence d'inhibiteur du transport d'acides organiques. Nous montrons que le profil de facteurs angiogéniques est influencé selon la localisation ce qui affecte directement l'organisation du réseau tubulaire ex vivo. Finalement, nous avons identifié une région conservée du GPR91 qui agit de signal de rétention. De plus, nous avons découvert l'effet de l'hypoxie sur la localisation.
Ces travaux confirment le rôle de régulateur maître de l'angiogenèse du GPR91 lors d'accumulation de succinate en condition hypoxique et démontrent pour la première fois l'existence, et l'importance, d'un récepteur intracellulaire activé par un intermédiaire du métabolisme. Ces données pavent donc la voie à une nouvelle avenue de traitement ciblant GPR91 dans des pathologies hypoxiques ischémiques cérébrales et soulèvent l'importance de tenir compte de la localisation subcellulaire de la cible dans le processus de découverte du médicament.The ability to adapt to the changing environment is essential for the survival of cells and organisms in general. The capacity to adjust to variations in oxygen content not only relies on the ability to sense hypoxia but also depends the time required to induce an angiogenic process. Notwithstanding the important contribution of the hypoxia inducible factor (HIF) in this response, other mechanisms are likely to be involved. Studies that have demonstrated the influence of metabolic compounds on vascular development are increasingly abundant. One of those compounds, succinate, has recently been indentified as the ligand of GPR91, a G-protein-coupled receptor. Amongst the roles of this receptor, our group has been interested in determining its contribution in revascularisation observed following hypoxic events in the retina. Other pathological conditions could benefit from the contribution of GPR91 including cerebral hypoxia-ischemia. Our objective is to better understand the role of this receptor during development and in pathological conditions affecting blood vessel formation. We first, determined the role of GPR91 in revascularisation following cerebral hypoxia-ischemia in the newborn. We show the expression of the receptor in the cerebral cortex. Using mice devoid of GPR91, we demonstrate that angiogenesis normally taking place during the recovery phase is largely dependent upon GPR91. Intracerebral injection of succinate induces the expression of several proangiogenic growth factors by activating GPR91. Furthermore, injection of succinate before cerebral H-I model substantially reduces the infarct size. In vitro, gene transcription shows that neurons and astrocytes respond to succinate and produce factors beneficial to revascularisation. Considering the important physiological role of GPR91, a second study was initiated to better determine the molecular determinants controlling the receptor's activity. The plasma membrane has classically been considered the typical GPCR's location of action but several new publications indicate the presence of such receptors within the cell. We observe, by confocal microscopy, the colocalisation of GPR91 (endogenous or transfected) with several marker of the endoplasmic reticulum. In addition, the gene induction observed when stimulated with succinate is severely affected in presence of the compound probenicid, an organic anion transporter inhibitor. We also demonstrate that the profile of genes expressed is largely dependent on the localisation of the receptor and consequently affects the organization of the tubular network ex vivo. Finally, we have identified a conserved region of GPR91 that acts as a retention signal. Lastly, we have uncovered the consequence of hypoxia affecting the post-translational modification of GPR91 and its change in location from the ER to the plasma membrane. This work confirms the role of GPR91 as a master regulator of angiogenesis in situations where succinate accumulates and demonstrated for the first time the existence, and importance, of an intracellular receptor activated by a metabolic intermediate. These results pave the way for future treatment targeting GPR91 in cerebral hypoxic ischemic pathologies and demonstrate the importance of taking into account the subcellular localisation in the drug discovery process.
Books on the topic "Krebs cycle metabolism"
1
Veech, Richard L., and M. Todd King. Alzheimer’s Disease. Edited by Detlev Boison. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780190497996.003.0026.
Full textAbstract:
Deficits in cerebral glucose utilization in Alzheimer’s disease (AD) arise decades before cognitive impairment and accumulation of amyloid plaques and neurofibrillary tangles in brain. Addressing this metabolic deficit has greater potential in treating AD than targeting later disease processes – an approach that has failed consistently in the clinic. Cerebral glucose utilization requires numerous enzymes, many of which have been shown to decline in AD. Perhaps the most important is pyruvate dehydrogenase (PDH), which links glycolysis with the Krebs cycle and aerobic metabolism, and whose activity is greatly suppressed in AD. The unique metabolism of ketone bodies allows them to bypass the block at pyruvate dehydrogenase and restore brain metabolism. Recent studies in mouse genetic models of AD and in a human Alzheimer’s patient showed the potential of ketones in maintaining brain energetics and function. Oral ketone bodies might be a promising avenue for treatment of Alzheimer’s disease.
Book chapters on the topic "Krebs cycle metabolism"
1
Fuchs, G. "Alternatives to the Calvin Cycle and the Krebs Cycle in Anaerobic Bacteria: Pathways with Carbonylation Chemistry." In The Molecular Basis of Bacterial Metabolism, 13–20. Berlin, Heidelberg: Springer Berlin Heidelberg, 1990. http://dx.doi.org/10.1007/978-3-642-75969-7_2.
Full text
2
Saavedra, Francisco, Ekaterina Boyarchuk, Francisca Alvarez, Geneviève Almouzni, and Alejandra Loyola. "Metabolic Deregulations Affecting Chromatin Architecture: One-Carbon Metabolism and Krebs Cycle Impact Histone Methylation." In RNA Technologies, 573–606. Cham: Springer International Publishing, 2019. http://dx.doi.org/10.1007/978-3-030-14792-1_23.
Full text
3
Morava, Eva, and Rosalba Carrozzo. "Disorders of the Krebs Cycle." In Physician's Guide to the Diagnosis, Treatment, and Follow-Up of Inherited Metabolic Diseases, 313–22. Berlin, Heidelberg: Springer Berlin Heidelberg, 2014. http://dx.doi.org/10.1007/978-3-642-40337-8_20.
Full text
4
"Cellular metabolism." In Oxford Handbook of Medical Sciences, edited by Robert Wilkins, Ian Megson, and David Meredith, 105–94. Oxford University Press, 2021. http://dx.doi.org/10.1093/med/9780198789895.003.0002.
Full textAbstract:
‘Cellular metabolism’ addresses the major biochemical pathways and processes of the cells of the body. These include the central metabolic pathways involved in energy production: the tricarboxylic acid or Krebs cycle, and ATP synthesis through the electron transport chain and oxidative phosphorylation (chemiosmotic theory). Metabolism of each of the major fuel sources is considered: lipids, carbohydrates, and proteins, including energy storage as fat and glycogen, and excretion of nitrogen via the urea cycle. The different cellular compartments for metabolism are explored, as is the integration and regulation of the metabolic processes in a number of conditions such as fasting and starvation, exercise, pregnancy, and diabetes. Finally in this chapter the clinical aspects of metabolism are discussed, including energy balance and nutrition, obesity, and inborn errors of metabolism.
5
Schulze, Almut, Karim Bensaad, and Adrian L. Harris. "Cancer metabolism." In Oxford Textbook of Cancer Biology, edited by Francesco Pezzella, Mahvash Tavassoli, and David J. Kerr, 221–38. Oxford University Press, 2019. http://dx.doi.org/10.1093/med/9780198779452.003.0016.
Full textAbstract:
Abnormalities in cancer metabolism have been noted since Warburg first described the phenomenon of glycolysis in normoxic conditions. This chapter reviews the major pathways in metabolism known to be modified in cancer, including glycolysis and the Krebs cycle, the pentose shunt, and new data implicating the role of different metabolic adaptations, including oncometabolism. It highlights the genetic changes that effect metabolism including many of the commonly occurring oncogenes but also rare mutations that specifically target metabolism. Nutrient and oxygen limitation and proliferation create the microenvironmental selective stress for modifications in hypoxic metabolism, but also affect other cell types such as endothelial cells and macrophages. This range of changes provides many new therapeutic approaches. It also describes the potential value of targeting these adaptations and approaches to monitoring in vivo effects in patients to monitor therapeutic activity.
6
"Cellular metabolism." In Oxford Assess and Progress: Medical Sciences, edited by Jade Chow, John Patterson, Kathy Boursicot, and David Sales. Oxford University Press, 2012. http://dx.doi.org/10.1093/oso/9780199605071.003.0014.
Full textAbstract:
Cellular metabolism is divided into catabolism — responsible for converting nutrients into the energy sources and smaller molecules required for the chemical reactions of the body — and anabolism, which is the interconversion and synthesis of the molecules that maintain the body’s structure and function. This chapter examines the control of metabolism and the central metabolic pathways. Such control includes compartmentalization of metabolic processes and the cooperation between the metabolic activities of different organs. Metabolic control is important because metabolism must match the availability of nutrients to the demand for the products of the metabolic processes and both will vary over time. The synthesis of adenosine triphosphate (ATP), with its high-energy phosphate bond, lies at the heart of these central metabolic pathways. Most of the ATP is produced by oxidative phosphorylation in the mitochondria, but glycolysis and the tricarboxylic acid cycle (also known as the citric acid cycle or Krebs cycle) provide additional amounts. Of the nutrients entering the body from the diet, fat, glucose, and amino acids are the main fuels for cellular metabolism. The utilization of lipids, fatty acids, and ketone bodies is important in metabolism in addition to the key role played by glucose. Glucose is the fuel for energy production in glycolysis. It is also manufactured by gluconeogenesis and stored as glycogen by glycogenesis. It is important to know how different organs utilize different fuels and how energy production alters between the fed state and starvation. Amino-acid metabolism and coenzymes in amino acid oxidation are also important although some details, including the urea cycle, have not been covered here. Energy balance and the relationship between food intake and energy expenditure lead to the concept of body mass index (BMI). The BMI offers a quick method of quantifying the nutritional status of a person, and BMI values may be helpful in assessing the risk of, for example, obesity-related diseases such as type II diabetes and coronary heart disease. Cellular metabolism not only contributes to the medical sciences background to clinical reasoning, but there are also a number of identifiable, inborn errors of metabolism. While individually rare (with incidences of approx. 1–25 per 100,000 births), collectively they present a considerable number of new cases each year.
7
Gomes Morais, Mariana, Francisca Guilherme Carvalho Dias, João Alexandre Velho Prior, Ana Luísa Pereira Teixeira, and Rui Manuel de Medeiros Melo Silva. "The Impact of Oxidoreductases-Related MicroRNAs in Glucose Metabolism of Renal Cell Carcinoma and Prostate Cancer." In Oxidoreductase. IntechOpen, 2021. http://dx.doi.org/10.5772/intechopen.93932.
Full textAbstract:
The reprogramming of metabolism is one of cancer hallmarks. Glucose’s metabolism, as one of the main fuels of cancer cells, has been the focus of several research studies in the oncology field. However, because cancer is a heterogeneous disease, the disruptions in glucose metabolism are highly variable depending of the cancer. In fact, Renal Cell Carcinoma (RCC) and Prostate Cancer (PCa), the most lethal and common urological neoplasia, respectively, show different disruptions in the main pathways of glucose catabolism: glycolysis, lactate fermentation and Krebs Cycle. Oxidoreductases are a class of enzymes that catalyze electrons transfer from one molecule to another and are present in these three pathways, posing as an opportunity to better understand these catabolic deregulations. Furthermore, nowadays it is recognized that their expression is modulated by microRNAs (miRNAs), in this book chapter, we selected the known miRNAs that directly target these oxidoreductases and analyzed their deregulation in both cancers. The characterization of these miRNAs opens a new door that could be applied in patients’ stratification and therapy monitorization because of their potential as cancer biomarkers. Additionally, their delivery to cancer cells, using glucose capped NPs could help establish new therapeutic strategies that would improve RCC and PCa management.
8
Ross, John, Igor Schreiber, and Marcel O. Vlad. "A Brief Review of Methodology for the Analysis of Biochemical Reactions and Cells." In Determination of Complex Reaction Mechanisms. Oxford University Press, 2006. http://dx.doi.org/10.1093/oso/9780195178685.003.0005.
Full textAbstract:
All cellular activities and responses to environmental stimuli are determined by a complex interplay of genes, RNA, proteins, and metabolites. As the observed phenotype is the result of all reactions occurring in the cell and with the environment, a comprehensive analytical representation of the biological system is required. The ideal analytical platform should identify and quantify, over time and in space, all possible species in a live cell and those trafficking with the environment. In addition, we expect the analysis not to interfere with the target. Because of the heterogeneity and number of species participating, such a platform does not exist yet. Nevertheless, the last decade has witnessed considerable technological advances, and a few systems have progressed sufficiently to support the understanding of cellular dynamics at a systemic level. The goal of this review is to provide the reader with a short survey on the instrumentation and techniques that are mostly contributing to this cause, and to elucidate their principles and applications. The experimental deduction of reaction mechanisms relies on the precise and accurate measurement of concentration changes of reacting species. With increasing system complexity, and thus number of analytes, separation methods are preferred to classical enzymatic assays, primarily for their capacity to analyze simultaneously a few to hundreds of compounds in one experiment. When considering a whole cell, this task is very challenging because thousands of different species, the metabolome, coexist, with very different chemical and physical characteristics. Generally, targeted methods are designed to quantify specific species within a class of related intermediates, such as sugar phosphates, hexosamines, purines, amino acids, and lipids. Since targeted methods are tailored to the specific chemical or spectral properties of a given class, they lead to improved resolution and detection limits. To date, most studies of cellular dynamics have focused on subsystems with a limited number of reactions or linked pathways. Analytes of interest typically belong to the same class and, thus, are accessible by a single analytical system. A prominent example are the intermediates of the central carbon metabolism, which comprises glycolysis, the pentose phosphate pathway, and the Krebs cycle.
9
Zhan, Xianquan, and Na Li. "The Anti-Cancer Effects of Anti-Parasite Drug Ivermectin in Ovarian Cancer." In Ovarian Cancer - Updates in Tumour Biology and Therapeutics [Working Title]. IntechOpen, 2021. http://dx.doi.org/10.5772/intechopen.95556.
Full textAbstract:
Ivermectin is an old, common, and classic anti-parasite drug, which has been found to have a broad-spectrum anti-cancer effect on multiple human cancers. This chapter will focus on the anti-cancer effects of ivermectin on ovarian cancer. First, ivermectin was found to suppress cell proliferation and growth, block cell cycle progression, and promote cell apoptosis in ovarian cancer. Second, drug pathway network, qRT-PCR, and immunoaffinity blot analyses found that ivermectin acts through molecular networks to target the key molecules in energy metabolism pathways, including PFKP in glycolysis, IDH2 and IDH3B in Kreb’s cycle, ND2, ND5, CYTB, and UQCRH in oxidative phosphorylation, and MCT1 and MCT4 in lactate shuttle, to inhibit ovarian cancer growth. Third, the integrative analysis of TCGA transcriptomics and mitochondrial proteomics in ovarian cancer revealed that 16 survival-related lncRNAs were mediated by ivermectin, SILAC quantitative proteomics analysis revealed that ivermectin extensively inhibited the expressions of RNA-binding protein EIF4A3 and 116 EIF4A3-interacted genes including those key molecules in energy metabolism pathways, and also those lncRNAs regulated EIF4A3-mRNA axes. Thus, ivermectin mediated lncRNA-EIF4A3-mRNA axes in ovarian cancer to exert its anticancer capability. Further, lasso regression identified the prognostic model of ivermectin-related three-lncRNA signature (ZNRF3-AS1, SOS1-IT1, and LINC00565), which is significantly associated with overall survival and clinicopathologic characteristics in ovarian cancer patients. These ivermectin-related molecular pattern alterations benefit for prognostic assessment and personalized drug therapy toward 3P medicine practice in ovarian cancer.
Conference papers on the topic "Krebs cycle metabolism"
1
Kho, Eun-Young, Carolina B. Livi, Phillip Buckhaults, Francesca Carobbio, Hye-Young Nam, Richard Kirkman, David Crossman, et al. "Abstract 53: Epigenetic silencing of krebs cycle metabolism in kidney cancer." In Proceedings: AACR 107th Annual Meeting 2016; April 16-20, 2016; New Orleans, LA. American Association for Cancer Research, 2016. http://dx.doi.org/10.1158/1538-7445.am2016-53.
Full text
2
Zhao, Liang, Matthew Arwood, Min-Hee Oh, Wei Xu, Im-Hong Sun, Im-Meng Sun, Chirag Patel, et al. "Abstract 4376: Targeting glutamine metabolism disables Warburg physiology by inhibiting proximal glycolysis and Krebs cycle rewiring." In Proceedings: AACR Annual Meeting 2019; March 29-April 3, 2019; Atlanta, GA. American Association for Cancer Research, 2019. http://dx.doi.org/10.1158/1538-7445.sabcs18-4376.
Full text
3
Zhao, Liang, Matthew Arwood, Min-Hee Oh, Wei Xu, Im-Hong Sun, Im-Meng Sun, Chirag Patel, et al. "Abstract 4376: Targeting glutamine metabolism disables Warburg physiology by inhibiting proximal glycolysis and Krebs cycle rewiring." In Proceedings: AACR Annual Meeting 2019; March 29-April 3, 2019; Atlanta, GA. American Association for Cancer Research, 2019. http://dx.doi.org/10.1158/1538-7445.am2019-4376.
Full text
4
Kuo, Ching-Chuan, Jang-Yang Chang, Hsing-Pang Hsieh, Hsing-Jien Kung, Hsih-Huei Chang, Chih-Hsiang Huang, Cheng-Chin Kuo, and Yi-Yu Ke. "Abstract 3944: Blockage of EGFR signaling repurposes tumor metabolism through suppression of glycolysis and Kreb cycle in head and neck cancer." In Proceedings: AACR Annual Meeting 2018; April 14-18, 2018; Chicago, IL. American Association for Cancer Research, 2018. http://dx.doi.org/10.1158/1538-7445.am2018-3944.
Full text