Related Research Articles
Glycolysis is the metabolic pathway that converts glucose into pyruvate. The free energy released in this process is used to form the high-energy molecules adenosine triphosphate (ATP) and reduced nicotinamide adenine dinucleotide (NADH). Glycolysis is a sequence of ten reactions catalyzed by enzymes. Capture of bond energy of carbohydrates. Storage of ATP
In biochemistry, a metabolic pathway is a linked series of chemical reactions occurring within a cell. The reactants, products, and intermediates of an enzymatic reaction are known as metabolites, which are modified by a sequence of chemical reactions catalyzed by enzymes. In most cases of a metabolic pathway, the product of one enzyme acts as the substrate for the next. However, side products are considered waste and removed from the cell. These enzymes often require dietary minerals, vitamins, and other cofactors to function.
Primary nutritional groups are groups of organisms, divided in relation to the nutrition mode according to the sources of energy and carbon, needed for living, growth and reproduction. The sources of energy can be light or chemical compounds; the sources of carbon can be of organic or inorganic origin.
Cellular respiration is the process by which biological fuels are oxidised in the presence of an inorganic electron acceptor such as oxygen to produce large amounts of energy, to drive the bulk production of ATP. Cellular respiration may be described as a set of metabolic reactions and processes that take place in the cells of organisms to convert chemical energy from nutrients into adenosine triphosphate (ATP), and then release waste products.
Bioenergetics is a field in biochemistry and cell biology that concerns energy flow through living systems. This is an active area of biological research that includes the study of the transformation of energy in living organisms and the study of thousands of different cellular processes such as cellular respiration and the many other metabolic and enzymatic processes that lead to production and utilization of energy in forms such as adenosine triphosphate (ATP) molecules. That is, the goal of bioenergetics is to describe how living organisms acquire and transform energy in order to perform biological work. The study of metabolic pathways is thus essential to bioenergetics.
Metabolic engineering is the practice of optimizing genetic and regulatory processes within cells to increase the cell's production of a certain substance. These processes are chemical networks that use a series of biochemical reactions and enzymes that allow cells to convert raw materials into molecules necessary for the cell's survival. Metabolic engineering specifically seeks to mathematically model these networks, calculate a yield of useful products, and pin point parts of the network that constrain the production of these products. Genetic engineering techniques can then be used to modify the network in order to relieve these constraints. Once again this modified network can be modeled to calculate the new product yield.
In oncology, the Warburg effect is the observation that most cancer cells produce energy predominantly not through the 'usual' citric acid cycle and oxidative phosphorylation in the mitochondria as observed in normal cells, but through a less efficient process of 'aerobic glycolysis' consisting of high level of glucose uptake and glycolysis followed by lactic acid fermentation taking place in the cytosol, not the mitochondria, even in the presence of abundant oxygen. This observation was first published by Otto Heinrich Warburg, who was awarded the 1931 Nobel Prize in Physiology for his "discovery of the nature and mode of action of the respiratory enzyme". The precise mechanism and therapeutic implications of the Warburg effect, however, remain unclear.
In biochemistry, mixed acid fermentation is the metabolic process by which a six-carbon sugar is converted into a complex and variable mixture of acids. It is an anaerobic (non-oxygen-requiring) fermentation reaction that is common in bacteria. It is characteristic for members of the Enterobacteriaceae, a large family of Gram-negative bacteria that includes E. coli.
Microbial metabolism is the means by which a microbe obtains the energy and nutrients it needs to live and reproduce. Microbes use many different types of metabolic strategies and species can often be differentiated from each other based on metabolic characteristics. The specific metabolic properties of a microbe are the major factors in determining that microbe's ecological niche, and often allow for that microbe to be useful in industrial processes or responsible for biogeochemical cycles.
Flux, or metabolic flux is the rate of turnover of molecules through a metabolic pathway. Flux is regulated by the enzymes involved in a pathway. Within cells, regulation of flux is vital for all metabolic pathways to regulate the pathway's activity under different conditions. Flux is therefore of great interest in metabolic network modelling, where it is analysed via flux balance analysis and metabolic control analysis.
The Warburg hypothesis, sometimes known as the Warburg theory of cancer, postulates that the driver of tumorigenesis is an insufficient cellular respiration caused by insult to mitochondria. The term Warburg effect in oncology describes the observation that cancer cells, and many cells grown in vitro, exhibit glucose fermentation even when enough oxygen is present to properly respire. In other words, instead of fully respiring in the presence of adequate oxygen, cancer cells ferment. The Warburg hypothesis was that the Warburg effect was the root cause of cancer. The current popular opinion is that cancer cells ferment glucose while keeping up the same level of respiration that was present before the process of carcinogenesis, and thus the Warburg effect would be defined as the observation that cancer cells exhibit glycolysis with lactate production and mitochondrial respiration even in the presence of oxygen.
The Pasteur effect describes how available oxygen inhibits ethanol fermentation, driving yeast to switch toward aerobic respiration for increased generation of the energy carrier adenosine triphosphate (ATP).
The Crabtree effect, named after the English biochemist Herbert Grace Crabtree, describes the phenomenon whereby the yeast, Saccharomyces cerevisiae, produces ethanol (alcohol) in aerobic conditions at high external glucose concentrations rather than producing biomass via the tricarboxylic acid (TCA) cycle, the usual process occurring aerobically in most yeasts e.g. Kluyveromyces spp. This phenomenon is observed in most species of the Saccharomyces, Schizosaccharomyces, Debaryomyces, Brettanomyces, Torulopsis, Nematospora, and Nadsonia genera. Increasing concentrations of glucose accelerates glycolysis which results in the production of appreciable amounts of ATP through substrate-level phosphorylation. This reduces the need of oxidative phosphorylation done by the TCA cycle via the electron transport chain and therefore decreases oxygen consumption. The phenomenon is believed to have evolved as a competition mechanism around the time when the first fruits on Earth fell from the trees. The Crabtree effect works by repressing respiration by the fermentation pathway, dependent on the substrate.
Fed-batch culture is, in the broadest sense, defined as an operational technique in biotechnological processes where one or more nutrients (substrates) are fed (supplied) to the bioreactor during cultivation and in which the product(s) remain in the bioreactor until the end of the run. An alternative description of the method is that of a culture in which "a base medium supports initial cell culture and a feed medium is added to prevent nutrient depletion". It is also a type of semi-batch culture. In some cases, all the nutrients are fed into the bioreactor. The advantage of the fed-batch culture is that one can control concentration of fed-substrate in the culture liquid at arbitrarily desired levels.
Metabolic flux analysis (MFA) is an experimental fluxomics technique used to examine production and consumption rates of metabolites in a biological system. At an intracellular level, it allows for the quantification of metabolic fluxes, thereby elucidating the central metabolism of the cell. Various methods of MFA, including isotopically stationary metabolic flux analysis, isotopically non-stationary metabolic flux analysis, and thermodynamics-based metabolic flux analysis, can be coupled with stoichiometric models of metabolism and mass spectrometry methods with isotopic mass resolution to elucidate the transfer of moieties containing isotopic tracers from one metabolite into another and derive information about the metabolic network. Metabolic flux analysis (MFA) has many applications such as determining the limits on the ability of a biological system to produce a biochemical such as ethanol, predicting the response to gene knockout, and guiding the identification of bottleneck enzymes in metabolic networks for metabolic engineering efforts.
Cofactor engineering, a subset of metabolic engineering, is defined as the manipulation of the use of cofactors in an organism’s metabolic pathways. In cofactor engineering, the concentrations of cofactors are changed in order to maximize or minimize metabolic fluxes. This type of engineering can be used to optimize the production of a metabolite product or to increase the efficiency of a metabolic network. The use of engineering single celled organisms to create lucrative chemicals from cheap raw materials is growing, and cofactor engineering can play a crucial role in maximizing production. The field has gained more popularity in the past decade and has several practical applications in chemical manufacturing, bioengineering and pharmaceutical industries.
Diauxic growth, diauxie or diphasic growth is any cell growth characterized by cellular growth in two phases. Diauxic growth, meaning double growth, is caused by the presence of two sugars on a culture growth media, one of which is easier for the target bacterium to metabolize. The preferred sugar is consumed first, which leads to rapid growth, followed by a lag phase. During the lag phase the cellular machinery used to metabolize the second sugar is activated and subsequently the second sugar is metabolized.
Aerobic fermentation or aerobic glycolysis is a metabolic process by which cells metabolize sugars via fermentation in the presence of oxygen and occurs through the repression of normal respiratory metabolism. It is referred to as the Crabtree effect in yeast. and is part of the Warburg effect in tumor cells. While aerobic fermentation does not produce adenosine triphosphate (ATP) in high yield, it allows proliferating cells to convert nutrients such as glucose and glutamine more efficiently into biomass by avoiding unnecessary catabolic oxidation of such nutrients into carbon dioxide, preserving carbon-carbon bonds and promoting anabolism.
Metabolite damage can occur through enzyme promiscuity or spontaneous chemical reactions. Many metabolites are chemically reactive and unstable and can react with other cell components or undergo unwanted modifications. Enzymatically or chemically damaged metabolites are always useless and often toxic. To prevent toxicity that can occur from the accumulation of damaged metabolites, organisms have damage-control systems that:
- Reconvert damaged metabolites to their original, undamaged form
- Convert a potentially harmful metabolite to a benign one
- Prevent damage from happening by limiting the build-up of reactive, but non-damaged metabolites that can lead to harmful products
Matthias Heinemann is a professor of molecular systems biology at the University of Groningen. Heinemann leads an interdisciplinary lab of approximately 12 graduate students and post-doctoral scholars. Until 2019, he served as the chairman of the Groningen Biomolecular Sciences and Biotechnology Institute, was a board member of the Dutch Origins Center and the coordinator of EU ITN project MetaRNA. Heinemann is a member of the Faculty of 1000.
References
- ↑ Vazquez, Alexei (2017-10-27). Overflow Metabolism: From Yeast to Marathon Runners. Academic Press. ISBN 9780128122082.
- ↑ Fernandez-de-Cossio-Diaz, Jorge; Vazquez, Alexei (2017-10-18). "Limits of aerobic metabolism in cancer cells". Scientific Reports. 7 (1): 13488. doi:10.1038/s41598-017-14071-y. ISSN 2045-2322. PMC 5647437 . PMID 29044214.
- ↑ Molenaar, Douwe; Berlo, Rogier van; Ridder, Dick de; Teusink, Bas (2009-01-01). "Shifts in growth strategies reflect tradeoffs in cellular economics". Molecular Systems Biology. 5 (1): 323. doi:10.1038/msb.2009.82. ISSN 1744-4292. PMC 2795476 . PMID 19888218.
- ↑ Basan, Markus; Hui, Sheng; Okano, Hiroyuki; Zhang, Zhongge; Shen, Yang; Williamson, James R.; Hwa, Terence (2015-12-03). "Overflow metabolism in Escherichia coli results from efficient proteome allocation". Nature. 528 (7580): 99–104. doi:10.1038/nature15765. ISSN 0028-0836. PMC 4843128 . PMID 26632588.
- 1 2 Heinemann, Matthias; Leupold, Simeon; Niebel, Bastian (January 2019). "An upper limit on Gibbs energy dissipation governs cellular metabolism" (PDF). Nature Metabolism. 1 (1): 125–132. doi:10.1038/s42255-018-0006-7. ISSN 2522-5812. PMID 32694810. S2CID 104433703.