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Zaragozic Acid
Zaragozic acids are a family of natural products produced by fungus, fungi. The first characterized zaragozic acids, A, B, and C were isolated from an unidentified sterile fungi, sterile fungal cell culture, culture, ''Sporormiella intermedia'', and ''Leptodontidium elatius var. elatius, L. elatius'', respectively. just outside the European city Zaragoza, Spain on the Jalón (river), Jalón river. This family of natural products possesses a unique 4,8-dioxabicyclo[3.2.1]octane core, and vary in their 1-alkyl and their 6-acyl side chains. Uses Zaragozic acids are potent enzyme inhibitor, inhibitors of ''Saccharomyces cerevisiae, S. cervisiae'', fungal and mammalian farnesyl-diphosphate farnesyltransferase, squalene synthase and therefore inhibitors of mevalonate pathway, sterol synthesis. Squalene synthase is the first committed enzyme in sterol synthesis, catalyzing the reductive condensation of farnesyl pyrophosphate to form squalene. As a squalene synthase inhibitor, zaragozic ac ...
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Natural Product
A natural product is a natural compound or substance produced by a living organism—that is, found in nature. In the broadest sense, natural products include any substance produced by life. Natural products can also be prepared by chemical synthesis (both semisynthesis and total synthesis) and have played a central role in the development of the field of organic chemistry by providing challenging synthetic targets. The term natural product has also been extended for commercial purposes to refer to cosmetics, dietary supplements, and foods produced from natural sources without added artificial ingredients. Within the field of organic chemistry, the definition of natural products is usually restricted to organic compounds isolated from natural sources that are produced by the pathways of primary or secondary metabolism. Within the field of medicinal chemistry, the definition is often further restricted to secondary metabolites. Secondary metabolites (or specialized metabolites ...
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Saccharomyces Cerevisiae
''Saccharomyces cerevisiae'' () (brewer's yeast or baker's yeast) is a species of yeast (single-celled fungus microorganisms). The species has been instrumental in winemaking, baking, and brewing since ancient times. It is believed to have been originally isolated from the skin of grapes. It is one of the most intensively studied eukaryotic model organisms in molecular biology, molecular and cell biology, much like ''Escherichia coli'' as the model bacteria, bacterium. It is the microorganism behind the most common type of fermentation (biochemistry), fermentation. ''S. cerevisiae'' cells are round to ovoid, 5–10 micrometre, μm in diameter. It reproduces by budding. Many proteins important in human biology were first discovered by studying their Homology (biology), homologs in yeast; these proteins include cell cycle proteins, signaling proteins, and protein-processing enzymes. ''S. cerevisiae'' is currently the only yeast cell known to have Berkeley body, Berkeley bo ...
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Polyketide Synthase
Polyketides are a class of natural products derived from a precursor molecule consisting of a chain of alternating ketone (or reduced forms of a ketone) and methylene groups: (-CO-CH2-). First studied in the early 20th century, discovery, biosynthesis, and application of polyketides has evolved. It is a large and diverse group of secondary metabolites caused by its complex biosynthesis which resembles that of fatty acid synthesis. Because of this diversity, polyketides can have various medicinal, agricultural, and industrial applications. Many polyketides are medicinal or exhibit acute toxicity. Biotechnology has enabled discovery of more naturally-occurring polyketides and evolution of new polyketides with novel or improved bioactivity. History Naturally produced polyketides by various plants and organisms have been used by humans since before studies on them began in the 19th and 20th century. In 1893, J. Norman Collie synthesized detectable amounts of orcinol by heating dehy ...
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Farnesyl Transferase
Farnesyltransferase () is one of the three enzymes in the prenyltransferase group. Farnesyltransferase (FTase) adds a 15-carbon isoprenoid called a farnesol, farnesyl group to proteins bearing a CaaX Sequence motif, motif: a four-amino acid sequence at the carboxyl terminus of a protein. Farnesyltransferase's targets include members of the Ras superfamily of GTPase, small GTP-binding proteins critical to cell cycle progression. For this reason, several Farnesyltransferase inhibitor, FTase inhibitors are undergoing testing as anti-cancer agents. FTase inhibitors have shown efficacy as anti-parasitic agents, as well. FTase is also believed to play an important role in development of progeria and various forms of cancers. Farnesyltransferase catalysis, catalyzes the chemical reaction :farnesyl diphosphate + protein-cysteine \rightleftharpoons S-farnesyl protein + diphosphate Thus, the two substrate (biochemistry), substrates of this enzyme are farnesyl diphosphate and protein-cystei ...
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MRNA
In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of Protein biosynthesis, synthesizing a protein. mRNA is created during the process of Transcription (biology), transcription, where an enzyme (RNA polymerase) converts the gene into primary transcript mRNA (also known as pre-mRNA). This pre-mRNA usually still contains introns, regions that will not go on to code for the final amino acid sequence. These are removed in the process of RNA splicing, leaving only exons, regions that will encode the protein. This exon sequence constitutes mature mRNA. Mature mRNA is then read by the ribosome, and, utilising amino acids carried by transfer RNA (tRNA), the ribosome creates the protein. This process is known as Translation (biology), translation. All of these processes form part of the central dogma of molecular biology, which describes the flow of genet ...
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LDL Receptor
The low-density lipoprotein receptor (LDL-R) is a mosaic protein of 839 amino acids (after removal of 21-amino acid signal peptide) that mediates the endocytosis of cholesterol-rich low-density lipoprotein (LDL). It is a cell-surface receptor that recognizes apolipoprotein B100 (ApoB100), which is embedded in the outer phospholipid layer of very low-density lipoprotein (VLDL), their remnants—i.e. intermediate-density lipoprotein (IDL), and LDL particles. The receptor also recognizes apolipoprotein E (ApoE) which is found in chylomicron remnants and IDL. In humans, the LDL receptor protein is encoded by the gene on chromosome 19. It belongs to the low density lipoprotein receptor gene family. It is most significantly expressed in bronchial epithelial cells and adrenal gland and cortex tissue. Michael S. Brown and Joseph L. Goldstein were awarded the 1985 Nobel Prize in Physiology or Medicine for their identification of LDL-R and its relation to cholesterol metabolism ...
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Cholesterol
Cholesterol is any of a class of certain organic molecules called lipids. It is a sterol (or modified steroid), a type of lipid. Cholesterol is biosynthesized by all animal cells and is an essential structural component of animal cell membranes. When chemically isolated, it is a yellowish crystalline solid. Cholesterol also serves as a precursor for the biosynthesis of steroid hormones, bile acid and vitamin D. Cholesterol is the principal sterol synthesized by all animals. In vertebrates, hepatic cells typically produce the greatest amounts. It is absent among prokaryotes (bacteria and archaea), although there are some exceptions, such as '' Mycoplasma'', which require cholesterol for growth. François Poulletier de la Salle first identified cholesterol in solid form in gallstones in 1769. However, it was not until 1815 that chemist Michel Eugène Chevreul named the compound "cholesterine". Etymology The word "cholesterol" comes from the Ancient Greek ''chole-'' ...
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Mevalonate Pathway
The mevalonate pathway, also known as the isoprenoid pathway or HMG-CoA reductase pathway is an essential metabolic pathway present in eukaryotes, archaea, and some bacteria. The pathway produces two five-carbon building blocks called isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP), which are used to make isoprenoids, a diverse class of over 30,000 biomolecules such as cholesterol, vitamin K, coenzyme Q10, and all steroid hormones. The mevalonate pathway begins with acetyl-CoA and ends with the production of IPP and DMAPP. It is best known as the target of statins, a class of cholesterol lowering drugs. Statins inhibit HMG-CoA reductase within the mevalonate pathway. Upper mevalonate pathway The mevalonate pathway of eukaryotes, archaea, and eubacteria all begin the same way. The sole carbon feed stock of the pathway is acetyl-CoA. The first step condenses two acetyl-CoA molecules to yield acetoacetyl-CoA. This is followed by a second condensation to for ...
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Farnesyl-diphosphate Farnesyltransferase
Squalene synthase (SQS) or farnesyl-diphosphate:farnesyl-diphosphate farnesyl transferase is an enzyme localized to the membrane of the endoplasmic reticulum. SQS participates in the isoprenoid biosynthetic pathway, catalyzing a two-step reaction in which two identical molecules of farnesyl pyrophosphate (FPP) are converted into squalene, with the consumption of NADPH. Catalysis by SQS is the first committed step in sterol synthesis, since the squalene produced is converted exclusively into various sterols, such as cholesterol, via a complex, multi-step pathway. SQS belongs to squalene/phytoene synthase family of proteins. Diversity Squalene synthase has been characterized in animals, plants, and yeast. In terms of structure and mechanics, squalene synthase closely resembles phytoene synthase (PHS), another prenyltransferase. PHS serves a similar role to SQS in plants and bacteria, catalyzing the synthesis of phytoene, a precursor of carotenoid compounds. Structure Squalene ...
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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. Reve ...
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Fungus
A fungus ( : fungi or funguses) is any member of the group of eukaryotic organisms that includes microorganisms such as yeasts and molds, as well as the more familiar mushrooms. These organisms are classified as a kingdom, separately from the other eukaryotic kingdoms, which by one traditional classification include Plantae, Animalia, Protozoa, and Chromista. A characteristic that places fungi in a different kingdom from plants, bacteria, and some protists is chitin in their cell walls. Fungi, like animals, are heterotrophs; they acquire their food by absorbing dissolved molecules, typically by secreting digestive enzymes into their environment. Fungi do not photosynthesize. Growth is their means of mobility, except for spores (a few of which are flagellated), which may travel through the air or water. Fungi are the principal decomposers in ecological systems. These and other differences place fungi in a single group of related organisms, named the ''Eumycota'' (''true f ...
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Jalón (river)
The river Jalón ( la, Salo) is located in the northeast of Spain, and is one of the principal tributaries of the Ebro. It has a length of and drains a basin of . The flow rate in Calatayud is , but is highly irregular due to the great range of Mediterranean rainfall patterns. The course of the river forms the main communication route between the Castilian Plateau and the Ebro. Until the late twentieth century, roads and railways between Madrid and Zaragoza followed this path. Geography The Jalón rises in one of the springs at the foot of the Sierra Ministra, a hill in Esteras de Medinaceli, Medinaceli (Soria), and then runs through Arcos de Jalón, to Monreal de Ariza, province of Zaragoza, Aragón. The tributary river Nágima joins at Monreal de Ariza and the Henar at Cetina before the river enters a limestone gorge at Alhama de Aragón. The Jalón then meanders through the Paleozoic zones of the Cordillera Ibérica near Bubierca, being joined by the Piedra and ...
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