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Cell Physiology
Published in Wei-Shou Hu, Cell Culture Bioprocess Engineering, 2020
Even fast-growing cells can be guided to a low flux state by controlling glucose at low levels. Such a glucose flux control in yeast has been known for decades as the Crabtree effect. Even with plenty of oxygen, Saccharomyces cerevisiae ferments glucose to ethanol if glucose is kept at high levels. By controlling glucose at low levels to reduce its consumption, cells return to an oxidative metabolism with a reduced glucose flux and without ethanol production. This approach of restricting glucose supply and controlling glucose at low levels to reduce glycolysis flux and thereby reduce lactate flux has been demonstrated in hybridoma and CHO cell culture. By controlling glucose at very low levels or by replacing glucose with another sugar such as galactose or fructose that is only taken up slowly, even fast-growing cells can be manipulated at a low flux state.1–4
Catabolite Regulation of the Main Metabolism
Published in Kazuyuki Shimizu, Metabolic Regulation and Metabolic Engineering for Biofuel and Biochemical Production, 2017
The increase in the glycolytic flux and the repression of the TCA cycle or the reduction in the respiratory capacity cause the formation of byproducts such as acetate in E. coli and ethanol in yeast, known as “overflow metabolism” (Wolfe 2005) or “Crabtree effect” (Crabtree 1929). In the case of yeast, the so-called Crabtree-positive species such as S. cerevisiae, S. bayanus, S. exiguous, Kluyveromyces thermotolerance show such phenomenon, while Crabtree-negative species such as Yarrowia lipolytica, Pichia angusta and Candida rugosa respire without overflow metabolism, where the glucose uptake rate for the latter species are all lower as compared to the former species (Christen and Sauer 2011). One of the short term events for Crabtree effect in yeast is an overflow through pyruvate decarboxylase (PDC), where the increased FBP in the upper glycolysis due to higher glucose consumption rate represses the mitochondrial oxidative phosphorylation, causing lower respiratory flux, where this phenomenon is also observed in the rat liver mitochondria (Diaz-Ruiz et al. 2008).
Outdoor Air Pollution
Published in William J. Rea, Kalpana D. Patel, Reversibility of Chronic Disease and Hypersensitivity, Volume 4, 2017
William J. Rea, Kalpana D. Patel
In 1929, Herbert Crabtree used mouse cancer cells to show that when glucose was added to a medium, oxygen consumption decreased.253 Mitochondria were not yet identified as the oxygen-consuming particles, but the iron and cytochrome-containing respiratory catalyst to describe the site of oxygen consumption in cells254 which was later discovered to be mitochondria. The Crabtree effect has been called the inverted Pasteur effect because in the Pasteur effect, exposure to oxygen was found to inhibit anaerobic glycolysis. The magnitude of the respiratory inhibition by glucose caused by the Crabtree effect varies between 5% and 50%255 depending on the cell type and the concentration of glucose added. The Crabtree effect plays an important role in many conditions, including chemical sensitivity and diabetes, in which persistently high levels of calories and glucose produce a relative decrease in mitochondrial oxygen consumption, resulting in weakness and fatigue. There are several biochemical mechanisms that combine to produce the Crabtree effect under conditions of nutrient loading.256 The most significant is the inhibitory effect of the cytosolically produced [ATP]/[ADP][Pk] ratio on mitochondrial ATP synthesis. This happens because mitochondrial oxidative phosphorylation requires cytosolic ADP and Pi to make ATP. When cytosolic ATP rises and ADFP falls, ADP becomes limiting in mitochondria and the excesses of cytosolic ATP inhibits the forward action of mitochondrial ATP synthase (complex V) by classic mechanisms of product inhibition. This induces a chemiosmotic backpressure of protons in the mitochondrial inner membrane space and hyperpolarizes the mitochondrial membrane, that is, makes the mitochondrial membrane potential (Δψm) more negative. Excess electrons that enter mitochondria under these conditions cannot be used to make ATP because of the backpressure. The partial reduction of oxygen to superoxide and peroxide serves as a pressure release valve257 that permits excess electrons to be dissipated and oxygen to be exported from the cell in the form of soluble hydrogen peroxide. All of these biophysical and thermodynamic consequences of nutrient loading result in a net decrease in mitochondrial oxygen consumption that we call the Crabtree effect. This effect explains why fasting periodically for 4–5 days helps right the metabolism's restoring energy to the chemically sensitive or chronic degenerative disease individual. With periodic fasting, even in skipping a meal or fasting for 1–2 days results in a return of energy and sharp brain function and elimination of weakness and fatigue.
Production and characterization of yeast extracts produced by Saccharomyces cerevisiae, Saccharomyces boulardii and Kluyveromyces marxianus
Published in Preparative Biochemistry & Biotechnology, 2022
Furkan Demirgül, Ömer Şimşek, Fatih Bozkurt, Enes Dertli, Osman Sağdıç
Yeasts convert sugar into CO2, energy and biomass if there is enough oxygen in the environment. However, high carbon (glucose and sucrose) concentration in the medium causes catabolite repression in yeasts known as Crabtree effect, resulting in less biomass production. For this reason, it is necessary to work in aerobic conditions and low sugar concentrations in order to produce high amounts of biomass.[29] In light of this information, wet yeast biomasses obtained as a result of fed-batch molasses fermentation performed under aerobic conditions for 42 h are shown in Table 1.