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Lethal Synthesis
Lethal synthesis, or suicide metabolism, is the biosynthesis of a toxin from a precursor which is not itself toxic, such as the synthesis of fluorocitrate from fluoroacetate or the synthesis of methylglyoxal from glycerol. The term was first publicised by Rudolph Peters in his Croonian Lecture of 1951. Lethal Synthesis of Methylglyoxal A 1971 study published by the Harvard Medical School identified methylglyoxal, a form of glycerol, as a product of lethal synthesis in a specific ''E.coli'' mutant. In ''E.coli,'' the synthesis of triose phosphate from glycerol is a reaction regulated by the synthesis rate of glycerol kinase and by feedback inhibition by fructose-1,6-bisphosphate. The study demonstrated that, in ''E.coli'' mutants that had lost both control mechanisms, glycerol kinase no longer reacted to feedback regulation and instead produced the cytotoxic methylglyoxal. A more recent review of research done on methylglyoxal metabolism concluded that the compound's cytotoxic na ...
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Compendium Of Chemical Terminology
The International Union of Pure and Applied Chemistry publishes many books which contain its complete list of definitions. The definitions are divided into seven "colour books": Gold, Green, Blue, Purple, Orange, White, and Red. There is also an eighth book—the "Silver Book". The eight ''colour books'' ''Blue Book'' ''Nomenclature of Organic Chemistry'', commonly referred to by chemists as the ''Blue Book'', is a collection of recommendations on organic chemical nomenclature published at irregular intervals by the International Union of Pure and Applied Chemistry (IUPAC). A full edition was published in 1979, an abridged and updated version of which was published in 1993 as ''A Guide to IUPAC Nomenclature of Organic Compounds''. Both of these are now out-of-print in their paper versions, but are available free of charge in electronic versions. After the release of a draft version for public comment in 2004 and the publication of several revised sections in the journal '' ...
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Escherichia Coli
''Escherichia coli'' (),Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. also known as ''E. coli'' (), is a Gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus '' Escherichia'' that is commonly found in the lower intestine of warm-blooded organisms. Most ''E. coli'' strains are harmless, but some serotypes ( EPEC, ETEC etc.) can cause serious food poisoning in their hosts, and are occasionally responsible for food contamination incidents that prompt product recalls. Most strains do not cause disease in humans and are part of the normal microbiota of the gut; such strains are harmless or even beneficial to humans (although these strains tend to be less studied than the pathogenic ones). For example, some strains of ''E. coli'' benefit their hosts by producing vitamin K2 or by preventing the colonization of the intestine by pathogenic bacteria. These mutually beneficial relationships between ''E. co ...
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Degenerative Disease
Degenerative disease is the result of a continuous process based on degenerative cell changes, affecting tissues or organs, which will increasingly deteriorate over time. In neurodegenerative diseases, cells of the central nervous system stop working or die via neurodegeneration. An example of this is Alzheimer's disease. The other two common groups of degenerative diseases are those that affect circulatory system (e.g. coronary artery disease) and neoplastic diseases (e.g. cancers). Many degenerative diseases exist and some are related to aging. Normal bodily wear or lifestyle choices (such as exercise or eating habits) may worsen degenerative diseases, but this depends on the disease. Sometimes the main or partial cause behind such diseases is genetic. Thus some are clearly hereditary like Huntington's disease. Sometimes the cause is viruses, poisons or other chemicals. The cause may also be unknown. Some degenerative diseases can be cured, but not always. It might still be ...
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Glycation
Glycation (sometimes called non-enzymatic glycosylation) is the covalent attachment of a sugar to a protein or lipid. Typical sugars that participate in glycation are glucose, fructose, and their derivatives. Glycation is the non-enzymatic process responsible for many (e.g. micro and macrovascular) complications in diabetes mellitus and is implicated in some diseases and in aging. Glycation end products are believed to play a causative role in the vascular complications of diabetes mellitus. In contrast with glycation, glycosylation is the enzyme-mediated ATP-dependent attachment of sugars to protein or lipid. Glycosylation occurs at defined sites on the target molecule. It is a common form of post-translational modification of proteins and is required for the functioning of the mature protein. Biochemistry Glycations occur mainly in the bloodstream to a small proportion of the absorbed simple sugars: glucose, fructose, and galactose. It appears that fructose has approximately ...
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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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Cytotoxicity
Cytotoxicity is the quality of being toxic to cells. Examples of toxic agents are an immune cell or some types of venom, e.g. from the puff adder (''Bitis arietans'') or brown recluse spider (''Loxosceles reclusa''). Cell physiology Treating cells with the cytotoxic compound can result in a variety of cell fates. The cells may undergo necrosis, in which they lose membrane integrity and die rapidly as a result of cell lysis. The cells can stop actively growing and dividing (a decrease in cell viability), or the cells can activate a genetic program of controlled cell death (apoptosis). Cells undergoing necrosis typically exhibit rapid swelling, lose membrane integrity, shut down metabolism, and release their contents into the environment. Cells that undergo rapid necrosis in vitro do not have sufficient time or energy to activate apoptotic machinery and will not express apoptotic markers. Apoptosis is characterized by well defined cytological and molecular events including a c ...
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Fructose 1,6-bisphosphate
Fructose 1,6-bisphosphate, also known as Harden-Young ester, is fructose sugar phosphorylated on carbons 1 and 6 (i.e., is a fructosephosphate). The β-D-form of this compound is common in cells. Upon entering the cell, most glucose and fructose is converted to fructose 1,6-bisphosphate. In glycolysis Fructose 1,6-bisphosphate lies within the glycolysis metabolic pathway and is produced by phosphorylation of fructose 6-phosphate. It is, in turn, broken down into two compounds: glyceraldehyde 3-phosphate and dihydroxyacetone phosphate. It is an allosteric activator of pyruvate kinase through distinct interactions of binding and allostery at the enzyme's catalytic site ''The numbering of the carbon atoms indicates the fate of the carbons according to their position in fructose 6-phosphate.'' Isomerism Fructose 1,6-bisphosphate has only one biologically active isomer, the β-D-form. There are many other isomers, analogous to those of fructose. Iron chelation Fru ...
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Enzyme Inhibitor
An enzyme inhibitor is a molecule that binds to an enzyme and blocks its activity. Enzymes are proteins that speed up chemical reactions necessary for life, in which substrate molecules are converted into products. An enzyme facilitates a specific chemical reaction by binding the substrate to its active site, a specialized area on the enzyme that accelerates the most difficult step of the reaction. An enzyme inhibitor stops ("inhibits") this process, either by binding to the enzyme's active site (thus preventing the substrate itself from binding) or by binding to another site on the enzyme such that the enzyme's catalysis of the reaction is blocked. Enzyme inhibitors may bind reversibly or irreversibly. Irreversible inhibitors form a chemical bond with the enzyme such that the enzyme is inhibited until the chemical bond is broken. By contrast, reversible inhibitors bind non-covalently and may spontaneously leave the enzyme, allowing the enzyme to resume its function. Rev ...
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Glycerol Kinase
Glycerol kinase, encoded by the gene ''GK'', is a phosphotransferase enzyme involved in triglycerides and glycerophospholipids synthesis. Glycerol kinase catalyzes the transfer of a phosphate from ATP to glycerol thus forming glycerol 3-phosphate: :ATP + glycerol ADP + ''sn''-glycerol 3-phosphate Adipocytes lack glycerol kinase so they cannot metabolize the glycerol produced during triacyl glycerol degradation. This glycerol is instead shuttled to the liver via the blood where it is: * Phosphorylated by glycerol kinase to glycerol 3-phosphate. * Converted from glycerol 3-phosphate to dihydroxyacetone phosphate (DHAP) via glycerol 3-phosphate dehydrogenase. DHAP can participate in glycolysis or gluconeogenesis. Enzyme regulation This protein may use the morpheein model of allosteric regulation. Structure Glycerol Kinase (alternative name, ATP:glycerol 3-phosphotransferase or Glycerokinase) adopts a ribonuclease H-like fold consisting of an alpha-beta 2-layer sandwich of ...
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Phosphate
In chemistry, a phosphate is an anion, salt, functional group or ester derived from a phosphoric acid. It most commonly means orthophosphate, a derivative of orthophosphoric acid . The phosphate or orthophosphate ion is derived from phosphoric acid by the removal of three protons . Removal of one or two protons gives the dihydrogen phosphate ion and the hydrogen phosphate ion ion, respectively. These names are also used for salts of those anions, such as ammonium dihydrogen phosphate and trisodium phosphate. File:3-phosphoric-acid-3D-balls.png, Phosphoricacid File:2-dihydrogenphosphate-3D-balls.png, Dihydrogenphosphate File:1-hydrogenphosphate-3D-balls.png, Hydrogenphosphate File:0-phosphate-3D-balls.png, Phosphate In organic chemistry, phosphate or orthophosphate is an organophosphate, an ester of orthophosphoric acid of the form where one or more hydrogen atoms are replaced by organic groups. An example is trimethyl phosphate, . The term also refers to the ...
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Mutant
In biology, and especially in genetics, a mutant is an organism or a new genetic character arising or resulting from an instance of mutation, which is generally an alteration of the DNA sequence of the genome or chromosome of an organism. It is a characteristic that would not be observed naturally in a specimen. The term mutant is also applied to a virus with an alteration in its nucleotide sequence whose genome is in the nuclear genome. The natural occurrence of genetic mutations is integral to the process of evolution. The study of mutants is an integral part of biology; by understanding the effect that a mutation in a gene has, it is possible to establish the normal function of that gene. Mutants arise by mutation Mutants arise by mutations occurring in pre-existing genomes as a result of errors of DNA replication or errors of DNA repair. Errors of replication often involve translesion synthesis by a DNA polymerase when it encounters and bypasses a damaged base in the t ...
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Harvard Medical School
Harvard Medical School (HMS) is the graduate medical school of Harvard University and is located in the Longwood Medical and Academic Area, Longwood Medical Area of Boston, Massachusetts. Founded in 1782, HMS is one of the oldest medical schools in the United States and is consistently ranked first for research among medical schools by ''U.S. News & World Report''. Unlike most other leading medical schools, HMS does not operate in conjunction with a single hospital but is directly affiliated with several teaching hospitals in the Boston area. Affiliated teaching hospitals and research institutes include Dana–Farber Cancer Institute, Massachusetts General Hospital, Brigham and Women's Hospital, Beth Israel Deaconess Medical Center, Boston Children's Hospital, McLean Hospital, Cambridge Health Alliance, The Baker Center for Children and Families, and Spaulding Rehabilitation Hospital. History Harvard Medical School was founded on September 19, 1782, after President Joseph Wi ...
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