Oncometabolism
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Oncometabolism
Oncometabolism is the field of study that focuses on the metabolic changes that occur in cells that make up the tumor microenvironment (TME) and accompany oncogenesis and tumor progression toward a neoplastic state. Cells with increased growth and survivability differ from non-tumorigenic cells in terms of metabolism. The Warburg Effect, which describes how cancer cells change their metabolism to become more oncogenic in order to proliferate and eventually invade other tissues in a process known as metastasis. The chemical reactions associated with oncometabolism are triggered by the alteration of oncogenes, which are genes that have the potential to cause cancer. These genes can be functional and active during physiological conditions, producing normal amounts of metabolites. Their upregulation as a result of DNA damage can result in an overabundance of these metabolites, and lead to tumorigenesis. These metabolites are known as oncometabolites, and can act as biomarkers. Hi ...
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Metabolism
Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cellular processes; the conversion of food to building blocks for proteins, lipids, nucleic acids, and some carbohydrates; and the elimination of metabolic wastes. These enzyme-catalyzed reactions allow organisms to grow and reproduce, maintain their structures, and respond to their environments. The word metabolism can also refer to the sum of all chemical reactions that occur in living organisms, including digestion and the transportation of substances into and between different cells, in which case the above described set of reactions within the cells is called intermediary (or intermediate) metabolism. Metabolic reactions may be categorized as '' catabolic'' – the ''breaking down'' of compounds (for example, of glucose to pyruvate ...
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Warburg Effect (oncology)
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 fermentation, the last product of glycolysis, pyruvate, is converted into lactate ( lactic acid fermentation) or ethanol ( alcoholic fermentation). While fermentation produces adenosine triphosphate (ATP) only in low yield ...
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Oncogene
An oncogene is a gene that has the potential to cause cancer. In tumor cells, these genes are often mutated, or expressed at high levels.Kimball's Biology Pages.
"Oncogenes" Free full text
Most normal cells will undergo a programmed form of rapid cell death () when critical functions are altered and malfunctioning. Activated oncogenes can cause those cells designated for apoptosis to survive and proliferate instead. Most oncogenes began as proto-oncogenes: normal genes involved in cell growth and proliferation or inhibition of apoptosis. If, through mutation, normal genes promoting cellular growth are up-regulated (gain-of-function mutation), they will predis ...
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Succinic Acid
Succinic acid () is a dicarboxylic acid with the chemical formula (CH2)2(CO2H)2. The name derives from Latin ''succinum'', meaning amber. In living organisms, succinic acid takes the form of an anion, succinate, which has multiple biological roles as a metabolic intermediate being converted into fumarate by the enzyme succinate dehydrogenase in complex 2 of the electron transport chain which is involved in making ATP, and as a signaling molecule reflecting the cellular metabolic state. It is marketed as food additive E363. Succinate is generated in mitochondria via the tricarboxylic acid cycle (TCA). Succinate can exit the mitochondrial matrix and function in the cytoplasm as well as the extracellular space, changing gene expression patterns, modulating epigenetic landscape or demonstrating hormone-like signaling. As such, succinate links cellular metabolism, especially ATP formation, to the regulation of cellular function. Dysregulation of succinate synthesis, and therefore ...
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Isocitrate Dehydrogenase
Isocitrate dehydrogenase (IDH) () and () is an enzyme that catalyzes the oxidative decarboxylation of isocitrate, producing alpha-ketoglutarate (α-ketoglutarate) and CO2. This is a two-step process, which involves oxidation of isocitrate (a secondary alcohol) to oxalosuccinate (a ketone), followed by the decarboxylation of the carboxyl group beta to the ketone, forming alpha-ketoglutarate. In humans, IDH exists in three isoforms: IDH3 catalyzes the third step of the citric acid cycle while converting NAD+ to NADH in the mitochondria. The isoforms IDH1 and IDH2 catalyze the same reaction outside the context of the citric acid cycle and use NADP+ as a cofactor instead of NAD+. They localize to the cytosol as well as the mitochondrion and peroxisome. Isozymes The following is a list of human isocitrate dehydrogenase isozymes: NADP+ dependent Each NADP+-dependent isozyme functions as a homodimer: See also * Isocitrate/isopropylmalate dehydrogenase family NAD+ depen ...
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Otto Heinrich Warburg
Otto Heinrich Warburg (, ; 8 October 1883 – 1 August 1970), son of physicist Emil Warburg, was a German physiologist, medical doctor, and Nobel laureate. He served as an officer in the elite Uhlan (cavalry regiment) during the First World War, and was awarded the Iron Cross (1st Class) for bravery. He was the sole recipient of the Nobel Prize in Physiology or Medicine in 1931. In total, he was nominated for the award 47 times over the course of his career. Biography Otto Heinrich Warburg was born in Freiburg im Breisgau in 1883, close to the Swiss border. Otto's mother was the daughter of a Protestant family of bankers and civil servants from Baden. His father, Emil Warburg, had converted to Protestantism as an adult, although Emil's parents were Orthodox Jews. Emil was a member of the illustrious Warburg family of Altona. Emil was also president of the ''Physikalische Reichsanstalt, Wirklicher Geheimer Oberregierungsrat'' (True Senior Privy Counselor). Otto Warburg studied c ...
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Oncogene
An oncogene is a gene that has the potential to cause cancer. In tumor cells, these genes are often mutated, or expressed at high levels.Kimball's Biology Pages.
"Oncogenes" Free full text
Most normal cells will undergo a programmed form of rapid cell death () when critical functions are altered and malfunctioning. Activated oncogenes can cause those cells designated for apoptosis to survive and proliferate instead. Most oncogenes began as proto-oncogenes: normal genes involved in cell growth and proliferation or inhibition of apoptosis. If, through mutation, normal genes promoting cellular growth are up-regulated (gain-of-function mutation), they will predis ...
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Metabolite
In biochemistry, a metabolite is an intermediate or end product of metabolism. The term is usually used for small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, catalytic activity of their own (usually as a cofactor to an enzyme), defense, and interactions with other organisms (e.g. pigments, odorants, and pheromones). A primary metabolite is directly involved in normal "growth", development, and reproduction. Ethylene exemplifies a primary metabolite produced large-scale by industrial microbiology. A secondary metabolite is not directly involved in those processes, but usually has an important ecological function. Examples include antibiotics and pigments such as resins and terpenes etc. Some antibiotics use primary metabolites as precursors, such as actinomycin, which is created from the primary metabolite tryptophan. Some sugars are metabolites, such as fructose or glucose, which a ...
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Biomolecule
A biomolecule or biological molecule is a loosely used term for molecules present in organisms that are essential to one or more typically biological processes, such as cell division, morphogenesis, or developmental biology, development. Biomolecules include large macromolecules (or polyelectrolytes) such as proteins, carbohydrates, lipids, and nucleic acids, as well as small molecules such as primary metabolites, secondary metabolites and natural products. A more general name for this class of material is biological materials. Biomolecules are an important element of living organisms, those biomolecules are often endogeny (biology), endogenous, produced within the organism but organisms usually need exogeny, exogenous biomolecules, for example certain nutrients, to survive. Biology and its subfields of biochemistry and molecular biology study biomolecules and their organic reaction, reactions. Most biomolecules are organic compounds, and just four chemical element, elements ...
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Amino Acid
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha amino acids appear in the genetic code. Amino acids can be classified according to the locations of the core structural functional groups, as Alpha and beta carbon, alpha- , beta- , gamma- or delta- amino acids; other categories relate to Chemical polarity, polarity, ionization, and side chain group type (aliphatic, Open-chain compound, acyclic, aromatic, containing hydroxyl or sulfur, etc.). In the form of proteins, amino acid '' residues'' form the second-largest component (water being the largest) of human muscles and other tissues. Beyond their role as residues in proteins, amino acids participate in a number of processes such as neurotransmitter transport and biosynthesis. It is thought that they played a key role in enabling l ...
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Lipid
Lipids are a broad group of naturally-occurring molecules which includes fats, waxes, sterols, fat-soluble vitamins (such as vitamins A, D, E and K), monoglycerides, diglycerides, phospholipids, and others. The functions of lipids include storing energy, signaling, and acting as structural components of cell membranes. Lipids have applications in the cosmetic and food industries, and in nanotechnology. Lipids may be broadly defined as hydrophobic or amphiphilic small molecules; the amphiphilic nature of some lipids allows them to form structures such as vesicles, multilamellar/unilamellar liposomes, or membranes in an aqueous environment. Biological lipids originate entirely or in part from two distinct types of biochemical subunits or "building-blocks": ketoacyl and isoprene groups. Using this approach, lipids may be divided into eight categories: fatty acyls, glycerolipids, glycerophospholipids, sphingolipids, saccharolipids, and polyketides (derived from cond ...
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Tumor Microenvironment
The tumor microenvironment (TME) is the environment around a tumor, including the surrounding blood vessels, immune cells, fibroblasts, signaling molecules and the extracellular matrix (ECM). The tumor and the surrounding microenvironment are closely related and interact constantly. Tumors can influence the microenvironment by releasing extracellular signals, promoting tumor angiogenesis and inducing peripheral immune tolerance, while the immune cells in the microenvironment can affect the growth and evolution of cancerous cells. History The importance of a stromal microenvironment, especially "wound" or regenerating tissue, has been recognized since the late 1800s. The interplay between the tumor and its microenvironment was part of Stephen Paget's 1889 "seed and soil" theory, in which he postulated that metastases of a particular type of cancer ("the seed") often metastasizes to certain sites ("the soil") based on the similarity of the original and secondary tumor site ...
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