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Discovery And Development Of Statins
The discovery of HMG-CoA (3-hydroxy-3-methylglutaryl-CoA) reductase inhibitors, called statins, was a breakthrough in the prevention of hypercholesterolemia and related diseases. Hypercholesterolemia is considered to be one of the major risk factors for atherosclerosis which often leads to cardiovascular, cerebrovascular and peripheral vascular diseases. The statins inhibit cholesterol synthesis in the body and that leads to reduction in blood cholesterol levels, which is thought to reduce the risk of atherosclerosis and diseases caused by it. History In the mid-19th century, a German pathologist named Rudolf Virchow discovered that cholesterol was to be found in the artery walls of people that died from occlusive vascular diseases, like myocardial infarction. The cholesterol was found to be responsible for the thickening of the arterial walls and thus decreasing the radius in the arteries which leads in most cases to hypertension and increased risk of occlusive vascular ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
HMG-CoA
β-Hydroxy β-methylglutaryl-CoA (HMG-CoA), also known as 3-hydroxy-3-methylglutaryl coenzyme A, is an intermediate in the mevalonate and ketogenesis pathways. It is formed from acetyl CoA and acetoacetyl CoA by HMG-CoA synthase. The research of Minor J. Coon and Bimal Kumar Bachhawat in the 1950s at University of Illinois led to its discovery. HMG-CoA is a metabolic intermediate in the metabolism of the branched-chain amino acids, which include leucine, isoleucine, and valine. Its immediate precursors are β-methylglutaconyl-CoA (MG-CoA) and β-hydroxy β-methylbutyryl-CoA (HMB-CoA). HMG-CoA reductase catalyzes the conversion of HMG-CoA to mevalonic acid, a necessary step in the biosynthesis of cholesterol. Biosynthesis Mevalonate pathway Mevalonate synthesis begins with the beta-ketothiolase-catalyzed Claisen condensation of two molecules of acetyl-CoA to produce acetoacetyl CoA. The following reaction involves the joining of acetyl-CoA and acetoacetyl-CoA to form HMG ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Enzyme
Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. Almost all metabolic processes in the cell need enzyme catalysis in order to occur at rates fast enough to sustain life. Metabolic pathways depend upon enzymes to catalyze individual steps. The study of enzymes is called ''enzymology'' and the field of pseudoenzyme analysis recognizes that during evolution, some enzymes have lost the ability to carry out biological catalysis, which is often reflected in their amino acid sequences and unusual 'pseudocatalytic' properties. Enzymes are known to catalyze more than 5,000 biochemical reaction types. Other biocatalysts are catalytic RNA molecules, called ribozymes. Enzymes' specificity comes from their unique three-dimensional structures. Like all catalysts, enzymes increase the reaction ra ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
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 ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Active Site
In biology and biochemistry, the active site is the region of an enzyme where substrate molecules bind and undergo a chemical reaction. The active site consists of amino acid residues that form temporary bonds with the substrate (binding site) and residues that catalyse a reaction of that substrate (catalytic site). Although the active site occupies only ~10–20% of the volume of an enzyme, it is the most important part as it directly catalyzes the chemical reaction. It usually consists of three to four amino acids, while other amino acids within the protein are required to maintain the tertiary structure of the enzymes. Each active site is evolved to be optimised to bind a particular substrate and catalyse a particular reaction, resulting in high specificity. This specificity is determined by the arrangement of amino acids within the active site and the structure of the substrates. Sometimes enzymes also need to bind with some cofactors to fulfil their function. The active si ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Endogenous
Endogenous substances and processes are those that originate from within a living system such as an organism, tissue, or cell. In contrast, exogenous substances and processes are those that originate from outside of an organism. For example, estradiol is an endogenous estrogen hormone produced within the body, whereas ethinylestradiol Ethinylestradiol (EE) is an estrogen medication which is used widely in birth control pills in combination with progestins. In the past, EE was widely used for various indications such as the treatment of menopausal symptoms, gynecological disord ... is an exogenous synthetic estrogen, commonly used in birth control pills. References External links *{{Wiktionary-inline, endogeny Biology ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Receptor Antagonist
A receptor antagonist is a type of receptor ligand or drug that blocks or dampens a biological response by binding to and blocking a receptor rather than activating it like an agonist. Antagonist drugs interfere in the natural operation of receptor proteins.Pharmacology Guide: In vitro pharmacology: concentration-response curves " '' GlaxoWellcome.'' Retrieved on December 6, 2007. They are sometimes called blockers; examples include alpha blockers, |
Lovastatin
Lovastatin, sold under the brand name Mevacor among others, is a statin medication, to treat hypercholesterolemia, high blood cholesterol and reduce the risk of cardiovascular disease. Its use is recommended together with lifestyle changes. It is taken by mouth. Common side effects include diarrhea, constipation, headache, muscles pains, rash, and trouble sleeping. Serious side effects may include liver problems, rhabdomyolysis, muscle breakdown, and kidney failure. Use during pregnancy may harm the baby and use during breastfeeding is not recommended. It works by decreasing the liver's ability to produce cholesterol by blocking the enzyme HMG-CoA reductase. Lovastatin was patented in 1979 and approved for medical use in 1987. It is on the WHO Model List of Essential Medicines, World Health Organization's List of Essential Medicines. It is available as a generic medication. In 2020, it was the 99th most commonly prescribed medication in the United States, with more than 7mill ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Aspergillus Terreus
''Aspergillus terreus'', also known as ''Aspergillus terrestris'', is a fungus (mold) found worldwide in soil. Although thought to be strictly asexual until recently, ''A. terreus'' is now known to be capable of sexual reproduction. This saprotrophic fungus is prevalent in warmer climates such as tropical and subtropical regions. Aside from being located in soil, ''A. terreus'' has also been found in habitats such as decomposing vegetation and dust. ''A. terreus'' is commonly used in industry to produce important organic acids, such as itaconic acid and ''cis''-aconitic acid, as well as enzymes, like xylanase. It was also the initial source for the drug mevinolin (lovastatin), a drug for lowering serum cholesterol. ''Aspergillus terreus'' can cause opportunistic infection in people with deficient immune systems. It is relatively resistant to amphotericin B, a common antifungal drug. ''Aspergillus terreus'' also produces aspterric acid and 6-hydroxymellein, inhibitors of pollen ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Clinical Trial
Clinical trials are prospective biomedical or behavioral research studies on human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel vaccines, drugs, dietary choices, dietary supplements, and medical devices) and known interventions that warrant further study and comparison. Clinical trials generate data on dosage, safety and efficacy. They are conducted only after they have received health authority/ethics committee approval in the country where approval of the therapy is sought. These authorities are responsible for vetting the risk/benefit ratio of the trial—their approval does not mean the therapy is 'safe' or effective, only that the trial may be conducted. Depending on product type and development stage, investigators initially enroll volunteers or patients into small pilot studies, and subsequently conduct progressively larger scale comparative studies. Clinical trials can vary i ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Animal Testing
Animal testing, also known as animal experimentation, animal research, and ''in vivo'' testing, is the use of non-human animals in experiments that seek to control the variables that affect the behavior or biological system under study. This approach can be contrasted with field studies in which animals are observed in their natural environments or habitats. Experimental research with animals is usually conducted in universities, medical schools, pharmaceutical companies, defense establishments, and commercial facilities that provide animal-testing services to the industry. The focus of animal testing varies on a continuum from pure research, focusing on developing fundamental knowledge of an organism, to applied research, which may focus on answering some questions of great practical importance, such as finding a cure for a disease. Examples of applied research include testing disease treatments, breeding, defense research, and toxicology, including cosmetics testing. In edu ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Mevastatin
Mevastatin (compactin, ML-236B) is a hypolipidemic agent that belongs to the statins class. It was isolated from the mold ''Penicillium citrinum'' by Akira Endo in the 1970s, and he identified it as a HMG-CoA reductase inhibitor, i.e., a statin. Mevastatin might be considered the first statin drug; clinical trials on mevastatin were performed in the late 1970s in Japan, but it was never marketed. The first statin drug available to the general public was lovastatin. Mevastatin has since been derivatized to the compound pravastatin, which is a pharmaceutical used in the lowering of cholesterol and preventing cardiovascular disease. ''In vitro'', it has antiproliferative properties. A British group isolated the same compound from ''Penicillium brevicompactum'', named it ''compactin'', and published their results in 1976. The British group mentions antifungal properties with no mention of HMG-CoA reductase inhibition. High doses inhibit growth and proliferation of melanoma cells ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Antimicrobial Agents And Chemotherapy
''Antimicrobial Agents and Chemotherapy'' is a peer-reviewed scientific journal published by the American Society for Microbiology. It covers antimicrobial, antiviral, antifungal, and antiparasitic agents and chemotherapy. The editor-in-chief is Cesar A. Arias (University of Texas Health Science Center at Houston). It was established in 1972 by Gladys Lounsbury Hobby. __TOC__ Abstracting and indexing The journal is abstracted and indexed in: According to the ''Journal Citation Reports'', its 2021 impact factor The impact factor (IF) or journal impact factor (JIF) of an academic journal is a scientometric index calculated by Clarivate that reflects the yearly mean number of citations of articles published in the last two years in a given journal, as i ... is 5.938, ranking it 51st out of 279 journals in the category ''Pharmacology & Pharmacy'' and 35th out of 137 journals in the category ''Microbiology''. References External links * Delayed open access journals Pu ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
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