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PCSK9
Proprotein convertase subtilisin/kexin type 9 (PCSK9) is an enzyme encoded by the ''PCSK9'' gene in humans on chromosome 1. It is the 9th member of the proprotein convertase family of proteins that activate other proteins. Similar genes ( orthologs) are found across many species. As with many proteins, PCSK9 is inactive when first synthesized, because a section of peptide chains blocks their activity; proprotein convertases remove that section to activate the enzyme. The ''PCSK9'' gene also contains one of 27 loci associated with increased risk of coronary artery disease. PCSK9 is ubiquitously expressed in many tissues and cell types. PCSK9 binds to and degrades the receptor for low-density lipoprotein particles (LDL), which typically transport 3,000 to 6,000 fat molecules (including cholesterol) per particle, within extracellular fluid. The LDL receptor (LDLR), on liver and other cell membranes, binds and initiates ingestion of LDL-particles from extracellular fluid into cel ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Alirocumab
Alirocumab, sold under the brand name Praluent, is a medication used as a second-line treatment for high cholesterol for adults whose cholesterol is not controlled by diet and statin treatment. It is a human monoclonal antibody that belongs to a novel class of anti-cholesterol drugs, known as PCSK9 inhibitors, and it was the first such agent to receive FDA approval. The FDA approval was contingent on the completion of further clinical trials to better determine efficacy and safety. Common side effects include nasopharyngitis (cold), injection site reactions, and influenza. It was approved for medical use in the United States and in the European Union in 2015. Medical uses Alirocumab is used as a second-line treatment to lower LDL cholesterol for adults who have a severe form of hereditary high cholesterol and people with atherosclerosis who require additional lowering of LDL cholesterol when diet and statin treatment have not worked. It is administered by subcutaneous inje ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Evolocumab
Evolocumab, sold under the brand name Repatha, is a monoclonal antibody that is an immunotherapy medication for the treatment of hyperlipidemia. Evolocumab is a fully human monoclonal antibody that inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9). PCSK9 is a protein that targets LDL receptors for degradation; its inhibition thereby enhances the liver's ability to remove LDL-C, often colloquially referred to as "bad" cholesterol, from the blood. Mechanism Evolocumab is designed to bind to PCSK9 and inhibit PCSK9 from binding to LDL receptors on the liver surface. In the absence of PCSK9, there are more LDL receptors on the surface of liver cells to remove LDL-C from the blood. Adverse effects Injection site reactions such as redness and pain are common and are reported in approximately 2.1–4.3% of cases. A reanalysis of the FOURIER trial based on regulatory data found that cardiac mortality with evolocumab was slightly higher than previously reported, however, ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Low-density Lipoprotein
Low-density lipoprotein (LDL) is one of the five major groups of lipoprotein that transport all fat molecules around the body in extracellular water. These groups, from least dense to most dense, are chylomicrons (aka ULDL by the overall density naming convention), very low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), low-density lipoprotein (LDL) and high-density lipoprotein (HDL). LDL delivers fat molecules to Cell (biology), cells. LDL has been associated with the progression of atherosclerosis. Overview Lipoproteins transfer lipids (fats) around the body in the extracellular fluid, making fats available to body cells for receptor-mediated endocytosis. Lipoproteins are complex particles composed of multiple proteins, typically 80–100 proteins per particle (organized by a single apolipoprotein B for LDL and the larger particles). A single LDL particle is about 22–27.5 nanometers in diameter, typically transporting 3,000 to 6,000 fat molecules per part ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Nabil Seidah
Nabil G. Seidah, (born 1949) is a Canadian Quebec, Québécois scientist. Born in Egypt, he was educated at Cairo University, and subsequently at Georgetown University where he obtained his Ph.D. in 1973. He emigrated to Canada and has been working at the Clinical Research Institute of Montreal (IRCM) since 1974. He is the director of the laboratory of Biochemical Neuroendocrinology. He discovered and cloned seven (PC1, PC2, PC4, PC5, PC7, SKI-1 and PCSK9) of the nine known enzymes belonging to the convertase family. During this period, he also greatly contributed to demonstrating that the proteolysis by the proprotein convertases is a wide mechanism that also concerns “non-neuropeptide” proteins such as growth factors, α-integrins, receptors, enzymes, membrane-bound transcription factors, and bacterial and viral proteins. In 2003, he discovered PCSK9 and showed that point mutations in the PCSK9 gene cause dominant familial hypercholesterolemia, likely because of a gain of f ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Proprotein Convertase
Proprotein convertases (PPCs) are a family of proteins that activate other proteins. Many proteins are inactive when they are first synthesized, because they contain chains of amino acids that block their activity. Proprotein convertases remove those chains and activate the protein. The prototypical proprotein convertase is furin. Proprotein convertases have medical significance, because they are involved in many important biological processes, such as cholesterol synthesis. Compounds called proprotein convertase inhibitors can block their action, and block the target proteins from becoming active. Many proprotein convertases, especially furin and PACE4, are involved in pathological processes such as viral infection, inflammation, hypercholesterolemia, and cancer, and have been postulated as therapeutic targets for some of these diseases. History The phenomenon of prohormone conversion was discovered by Donald F. Steiner while examining the biosynthesis of insulin in 1967. At ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Cholesterol
Cholesterol is the principal sterol of all higher animals, distributed in body Tissue (biology), tissues, especially the brain and spinal cord, and in Animal fat, animal fats and oils. Cholesterol is biosynthesis, biosynthesized by all animal Cell (biology)#Eukaryotic cells, cells and is an essential structural and cholesterol signaling, signaling component of animal cell membranes. In vertebrates, hepatocyte, hepatic cells typically produce the greatest amounts. In the brain, astrocytes produce cholesterol and transport it to neurons. It is absent among prokaryotes (bacteria and archaea), although there are some exceptions, such as ''Mycoplasma'', which require cholesterol for growth. Cholesterol also serves as a Precursor (chemistry), precursor for the biosynthesis of steroid hormones, bile acid and vitamin D. Elevated levels of cholesterol in the blood, especially when bound to low-density lipoprotein (LDL, often referred to as "bad cholesterol"), may increase the risk of ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
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 metaboli ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Enzyme
An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different molecules known as product (chemistry), products. Almost all metabolism, metabolic processes in the cell (biology), 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, 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 include Ribozyme, catalytic RNA molecules, also called ribozymes. They are sometimes descr ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Homeostasis
In biology, homeostasis (British English, British also homoeostasis; ) is the state of steady internal physics, physical and chemistry, chemical conditions maintained by organism, living systems. This is the condition of optimal functioning for the organism and includes many variables, such as body temperature and fluid balance, being kept within certain pre-set limits (homeostatic range). Other variables include the pH of extracellular fluid, the concentrations of sodium, potassium, and calcium ions, as well as the blood sugar level, and these need to be regulated despite changes in the environment, diet, or level of activity. Each of these variables is controlled by one or more regulators or homeostatic mechanisms, which together maintain life. Homeostasis is brought about by a natural resistance to change when already in optimal conditions, and equilibrium is maintained by many regulatory mechanisms; it is thought to be the central motivation for all organic action. All home ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Journal Of The American College Of Cardiology
The ''Journal of the American College of Cardiology'' is a peer-reviewed medical journal covering all aspects of cardiovascular disease, including original clinical studies, translational investigations with clear clinical relevance, state-of-the-art papers, review articles, and editorials interpreting and commenting on the research presented, published by the American College of Cardiology. Abstracting and indexing The journal is abstracted and indexed in Current Contents, EMBASE, MEDLINE, Science Citation Index, and Scopus. According to the ''Journal Citation Reports'', the journal has a 2020 impact factor of 24.094, ranking it 4th out of 141 journals in the category "Cardiac & Cardiovascular Systems". Associated journals * ''JACC: Basic to Translational Science'' (Impact Factor: 8.4) * ''JACC: CardioOncology'' (Impact Factor: 12) * '' JACC: Cardiovascular Imaging'' (Impact Factor: 12.8) * '' JACC: Cardiovascular Interventions'' (Impact Factor: 11.7) * ''JACC: Clinical Ele ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Statin
Statins (or HMG-CoA reductase inhibitors) are a class of medications that lower cholesterol. They are prescribed typically to people who are at high risk of cardiovascular disease. Low-density lipoprotein (LDL) carriers of cholesterol play a key role in the development of atherosclerosis and coronary heart disease via the mechanisms described by the lipid hypothesis. As lipid-lowering medications, statins are effective in lowering LDL cholesterol; they are widely used for primary prevention in people at high risk of cardiovascular disease, as well as in secondary prevention for those who have developed cardiovascular disease. Side effects of statins include muscle pain, increased risk of diabetes, and abnormal blood levels of certain liver enzymes. Additionally, they have rare but severe adverse effects, particularly muscle damage, and very rarely rhabdomyolysis. They act by inhibiting the enzyme HMG-CoA reductase, which plays a central role in the production of ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Journal Of Lipid Research
The ''Journal of Lipid Research'' is a monthly peer-reviewed open access scientific journal that was established in 1959. Since 2000, it has been published by the American Society for Biochemistry and Molecular Biology. It covers research on lipids in health and disease, including lipid function and the biochemical and genetic regulation of lipid metabolism. The journal also covers patient-oriented and epidemiological research. In its aim and scope, the journal "''aims to be on the forefront of the emerging areas of genomics, proteomics, metabolomics, and lipidomics as they relate to lipid metabolism and function.''" The journal is published in print and online. As of February 1, 2019, its editors-in-chief are Kerry-Anne Rye and Nick Davidson. The journal was established in response to the lack of published methodologies in lipid research as perceived by Edward H. Ahrens, Jr., Donald Zilversmit, and others, who founded Lipid Research Inc. to publish the journal. Prior to its c ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
