Cycle de Krebs | EPFL Graph Search

Le cycle de Krebs, aussi appelé cycle de l'acide citrique par anglicisme, est une voie métabolique présente chez tous les organismes aérobies et dont la fonction première est d'oxyder les groupes acétyle, issus notamment de la dégradation des glucides, des lipides et des protéines, pour en récupérer l'énergie sous forme de huit électrons à haut potentiel de transfert et d'une molécule de GTP ou d'ATP ; les électrons à haut potentiel de transfert, récupérés sur le NADH et l'ubiquinol (, ou coenzyme réduite), circulent ensuite à travers la chaîne respiratoire pour former à leur tour des molécules d’ATP supplémentaires par la phosphorylation oxydative. Ce cycle a été découvert par étapes dans les années 1930, plusieurs de ses éléments ayant été identifiés par le biologiste moléculaire hongrois Albert Szent-Györgyi tandis que son fonctionnement cyclique était mis en évidence par le biochimiste allemand Hans Adolf Krebs en 1937. Il se déroule dans le cytoplasme des procaryotes et dans l

Bioactive Compounds of Juice and Peels of Yuzu Fruits Cultivated in Switzerland

Aurélie Sprunger

Yuzu is a citrus fruit cultivated mainly in northeast Asia. Due to the huge gastronomic interest emerging in recent years, some attempts to grow yuzu in Europe are being made. Juice and peel of yuzu cultivated in Switzerland have been characterised in this study. Peel constituted the major part of yuzu fruit followed by flesh, juice and seeds. The fruit degree of maturity was investigated by measuring pH, total titratable acidity and total soluble solids of the juice. The analyses were pursued by determining the content of vitamin C, malic and citric acids amounting to 0.560, 6.18 and 44.7 g/L, respectively. Four flavanones: naringin, hesperidin, naringenin, and hesperetin were identified and quantified in both juice and peel. The most abundant flavanone was hesperidin with 47 mu g/mL and 640 mu g/g dry matter (DM) in juice and peel, respectively. For the first time yuzu grown in Switzerland have been analysed and the obtained values have been compared with literature for other citrus fruits. Yuzu juice showed higher contents of citric and malic acid. Yuzu cultivated in Switzerland contained nearly twice as much vitamin C as yuzu juices from different regions of Japan. The content of vitamin C of yuzu was as high or higher than in most other citrus fruits. Large differences in the content of flavanones in yuzu juice from different regions of Japan were reported, in general the values noted were lower than those in the present study.

2018

Role of the cystathionine beta-synthase / H2S pathway in the development of cellular metabolic dysfunction and pseudohypoxia in down syndrome

Theodora Panagaki

Background: Overexpression of the transsulfuration enzyme cystathionine-beta-synthase (CBS), and overproduction of its product, hydrogen sulfide (H2S) are recognized as potential pathogenetic factors in Down syndrome (DS). The purpose of the study was to determine how the mitochondrial function and core metabolic pathways are affected by DS and how pharmacological inhibition of CBS affects these parameters. Methods: 8 human control and 8 human DS fibroblast cell lines have been subjected to bioenergetic and fluxomic and proteomic analysis with and without treatment with a pharmacological inhibitor of CBS. Results: DS cells exhibited a significantly higher CBS expression than control cells, and produced more H2S. They also exhibited suppressed mitochondrial electron transport and oxygen consumption and suppressed Complex IV activity, impaired cell proliferation and increased ROS generation. Inhibition of H2S biosynthesis with aminooxyacetic acid reduced cellular H2S, improved cellular bioenergetics, attenuated ROS and improved proliferation. C-13 glucose fluxomic analysis revealed that DS cells exhibit a suppression of the Krebs cycle activity with a compensatory increase in glycolysis. CBS inhibition restored the flux from glycolysis to the Krebs cycle and reactivated oxidative phosphorylation. Proteomic analysis revealed no CBS-dependent alterations in the expression level of the enzymes involved in glycolysis, oxidative phosphorylation and the pentose phosphate pathway. DS was associated with the dysregulation of several components of the autophagy network; CBS inhibition normalized several of these parameters. Conclusions: Increased H2S generation in DS promotes pseudohypoxia and contributes to cellular metabolic dysfunction by causing a shift from oxidative phosphorylation to glycolysis.

ELSEVIER2022

Mechanical Activation of Chemical Bonds at Polymer Interfaces

Julian Nicolas Bleich

Polymer brushes are a specific class of polymer thin films in which each chain is tethered to the underlying substrate via one chain end. In sufficiently densely grafted assemblies, the individual polymer chains are forced into an extended chain conformation and form a brush-like structure, colloquially referred to as polymer brush. Upon incubation in a good solvent, polymer brushes experience swelling which leads to a tension at the polymer brush - substrate interface. This tension is believed to mechanically facilitate cleaving reactions at the tethering point resulting in the detachment of polymer chains, a process which is known as degrafting. Degrafting, and in the case of crosslinked polymer brushes delamination, has been reported for a large variety of polymer brushes and surface materials. Even though this phenomenon is already known for more than two decades, in depth understanding of the underlying mechanism is lacking and quantitative description of the process is rare. This thesis aims to gain further understanding of the phenomenon by quantitative description of the degrafting process. Further, swelling induced mechanical activation at the tethering point of the polymer to the underlying substrate is discussed in the context of polymer mechanochemistry and presented as a tool to selectively facilitate mechanophore cleavage at the interface. Chapter 1 provides a short historical review on the development of polymer mechanochemistry and gives an overview of commonly applied techniques in the field. The concept of polymer mechanochemistry is then extended to polymer brushes and the discussion results in a number of issues and research questions which are addressed in the subsequent chapters. The preparation and characterization of polymer brushes is not trivial. In Chapter 2 limitations and challenges with focus on experimental reproducibility and thin film characterization are discussed. Chapter 3 discusses the influence of a number of factors, i.e. grafting density and molecular weight of the polymer brush, solvent quality and salt concentration in the incubation medium, on the degrafting process of hydrophilic brushes in aqueous media. Further, the degrafting behavior of polymer brushes prepared from different monomers is compared. It is attempted to correlate degrafting behavior with polymer brush swelling. Contradicting results concerning the actual cleaving point of chains in polymer brushes are found in literature. In Chapter 4 presents structures incorporating only one single potential cleaving point. However, non-specific degrafting could not completely be suppressed. Further, a disulfide bond and oxy-norbornene moiety, commonly used mechanophores, were introduced at the anchoring point. In Chapter 5 the limitation of unwanted background hydrolysis was circumvented by investigating degrafting processes in dry organic media. Specific cleavage of the two mechanophores, disulfide and oxy-norbornene, could be demonstrated.

EPFL2021

Mechanical Activation of Chemical Bonds at Polymer Interfaces

Julian Nicolas Bleich

EPFL2021