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Urate Transporter Inhibitor
Solute carrier family 22 (organic anion/cation transporter), member 12, also known as SLC22A12 and URAT1, is a protein which in humans is encoded by the ''SLC22A12'' gene. Function The protein encoded by this gene is a urate transporter and urate-anion exchanger which regulates the level of urate in the blood. This protein is an integral membrane protein primarily found in kidney. Two transcript variants encoding different isoforms have been found for this gene. Clinical significance Numerous single nucleotide polymorphisms of this gene are significantly associated with altered (increased or decreased) reabsorption of uric acid by the kidneys. Respectively, these altered rates of reabsorption contribute to hyperuricemia and hypouricemia. Interactions SLC22A12 has been shown to interact with PDZK1. Inhibition Lesinurad and dotinurad are urate transporter inhibitors that have been approved to treat gout. Lesinurad enhances urate excretion by inhibition the tubular re-abso ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, responding to stimuli, providing structure to cells and organisms, and transporting molecules from one location to another. Proteins differ from one another primarily in their sequence of amino acids, which is dictated by the nucleotide sequence of their genes, and which usually results in protein folding into a specific 3D structure that determines its activity. A linear chain of amino acid residues is called a polypeptide. A protein contains at least one long polypeptide. Short polypeptides, containing less than 20–30 residues, are rarely considered to be proteins and are commonly called peptides. The individual amino acid residues are bonded together by peptide bonds and adjacent amino acid residues. The sequence of amino acid residue ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a basic unit of heredity and the molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protein-coding genes and noncoding genes. During gene expression, the DNA is first copied into RNA. The RNA can be directly functional or be the intermediate template for a protein that performs a function. The transmission of genes to an organism's offspring is the basis of the inheritance of phenotypic traits. These genes make up different DNA sequences called genotypes. Genotypes along with environmental and developmental factors determine what the phenotypes will be. Most biological traits are under the influence of polygenes (many different genes) as well as gen ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Uric Acid
Uric acid is a heterocyclic compound of carbon, nitrogen, oxygen, and hydrogen with the formula C5H4N4O3. It forms ions and salts known as urates and acid urates, such as ammonium acid urate. Uric acid is a product of the metabolic breakdown of purine nucleotides, and it is a normal component of urine. High blood concentrations of uric acid can lead to gout and are associated with other medical conditions, including diabetes and the formation of ammonium acid urate kidney stones. Chemistry Uric acid was first isolated from kidney stones in 1776 by Swedish chemist Carl Wilhelm Scheele. In 1882, the Ukrainian chemist Ivan Horbaczewski first synthesized uric acid by melting urea with glycine. Uric acid displays lactam–lactim tautomerism (also often described as keto–enol tautomerism). Although the lactim form is expected to possess some degree of aromaticity, uric acid crystallizes in the lactam form, with computational chemistry also indicating that tautomer to be the most s ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Integral Membrane Protein
An integral, or intrinsic, membrane protein (IMP) is a type of membrane protein that is permanently attached to the biological membrane. All ''transmembrane proteins'' are IMPs, but not all IMPs are transmembrane proteins. IMPs comprise a significant fraction of the proteins encoded in an organism's genome. Proteins that cross the membrane are surrounded by annular lipids, which are defined as lipids that are in direct contact with a membrane protein. Such proteins can only be separated from the membranes by using detergents, nonpolar solvents, or sometimes denaturing agents. Structure Three-dimensional structures of ~160 different integral membrane proteins have been determined at atomic resolution by X-ray crystallography or nuclear magnetic resonance spectroscopy. They are challenging subjects for study owing to the difficulties associated with extraction and crystallization. In addition, structures of many water-soluble protein domains of IMPs are available in the Prote ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Single Nucleotide Polymorphism
In genetics, a single-nucleotide polymorphism (SNP ; plural SNPs ) is a germline substitution of a single nucleotide at a specific position in the genome. Although certain definitions require the substitution to be present in a sufficiently large fraction of the population (e.g. 1% or more), many publications do not apply such a frequency threshold. For example, at a specific base position in the human genome, the G nucleotide may appear in most individuals, but in a minority of individuals, the position is occupied by an A. This means that there is a SNP at this specific position, and the two possible nucleotide variations – G or A – are said to be the alleles for this specific position. SNPs pinpoint differences in our susceptibility to a wide range of diseases, for example age-related macular degeneration (a common SNP in the CFH gene is associated with increased risk of the disease) or nonalcoholic fatty liver disease (a SNP in the PNPLA3 gene is associated with incr ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Hyperuricemia
Hyperuricaemia or hyperuricemia is an abnormally high level of uric acid in the blood. In the pH conditions of body fluid, uric acid exists largely as urate, the ion form. Serum uric acid concentrations greater than 6 mg/dL for females, 7 mg/dL for men, and 5.5 mg/dL for youth (under 18 years old) are defined as hyperuricemia. The amount of urate in the body depends on the balance between the amount of purines eaten in food, the amount of urate synthesised within the body (e.g., through cell turnover), and the amount of urate that is excreted in urine or through the gastrointestinal tract. Hyperuricemia may be the result of increased production of uric acid, decreased excretion of uric acid, or both increased production and reduced excretion. Signs and symptoms Unless high blood levels of uric acid are determined in a clinical laboratory, hyperuricemia may not cause noticeable symptoms in most people. Development of gout which is a painful, short-term disorder is ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Hypouricemia
Hypouricemia or hypouricaemia is a level of uric acid in blood serum that is below normal. In humans, the normal range of this blood component has a lower threshold set variously in the range of 2 mg/dL to 4 mg/dL, while the upper threshold is 530 μmol/L (6 mg/dL) for women and 619 μmol/L (7 mg/dL) for men. Hypouricemia usually is benign and sometimes is a sign of a medical condition. Presentation Complications Although normally benign, idiopathic renal hypouricemia may increase the risk of exercise-induced acute kidney failure. There is also evidence that hypouricemia can worsen conditions such as rheumatoid arthritis, especially when combined with low Vitamin C uptake, due to free radical damage. Causes Hypouricemia is not a medical condition itself (i.e., it is benign), but it is a useful medical sign. Usually hypouricemia is due to drugs and toxic agents, sometimes it is due to diet or genetics, and rarely it is due to an underlying medical condition. ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
PDZK1
Na(+)/H(+) exchange regulatory cofactor NHE-RF3 is a protein that in humans is encoded by the ''PDZK1'' gene. Interactions PDZK1 has been shown to interact with: * AKAP10, * CLCN3, * Cystic fibrosis transmembrane conductance regulator * FARP2, * PDZK1IP1, * SLC22A12, * SLC22A4, * SLC34A3, * SLK, and * Sodium-hydrogen antiporter 3 regulator 1. Related gene problems *TAR syndrome *1q21.1 deletion syndrome *1q21.1 duplication syndrome 1q21.1 duplication syndrome or 1q21.1 (recurrent) microduplication is a rare aberration of chromosome 1. In a common situation a human cell has one pair of identical chromosomes on chromosome 1. With the 1q21.1 duplication syndrome one chromosome ... References Further reading * * * * * * * * * * * * * * * * {{protein-stub ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Lesinurad
Lesinurad (brand name Zurampic) is a urate transporter inhibitor for treating high blood uric acid levels associated with gout. It is only recommended together with either allopurinol or febuxostat when these medications are not sufficient. It received FDA approval on 22 December 2015. The European Commission granted a marketing authorisation valid throughout the European Union on 18 February 2016. In February 2019, it was discontinued in the United States by its manufacturer for business reasons, and was subsequently withdrawn in Europe in July 2020. Medical uses Lesinurad is used in combination with a xanthine oxidase inhibitor, such as allopurinol or febuxostat, for treating hyperuricemia (high levels of uric acid in the blood serum) associated with gout. It is approved only for patients who have not achieved target uric acid levels with a xanthine oxidase inhibitor alone. Contraindications The drug is contraindicated in people with tumour lysis syndrome or Lesch–Nyhan ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Dotinurad
Dotinurad (Urece) is a drug for the treatment of gout and hyperuricemia. It was developed by Fuji Yakuhin and approved for use in Japan in 2020. The drug is continuing clinical trials by Fortress Biotech and regulatory evaluation for approval in North America and Europe. Dotinurad acts as a selective urate reabsorption inhibitor that has uric acid Uric acid is a heterocyclic compound of carbon, nitrogen, oxygen, and hydrogen with the formula C5H4N4O3. It forms ions and salts known as urates and acid urates, such as ammonium acid urate. Uric acid is a product of the metabolic breakdown ... lowering activity. References {{reflist Antigout agents Phenols Chlorobenzenes Benzothiazoles ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Pharmaceuticals And Medical Devices Agency
The (PhMDA) is an Independent Administrative Institution responsible for ensuring the safety, efficacy and quality of pharmaceuticals and medical devices in Japan. It is similar in function to the Food and Drug Administration in the United States, the Medicines and Healthcare products Regulatory Agency in the United Kingdom or the Food and Drug Administration in the Philippines. The PhMDA has been eCTD compliant at least since December 2017. Tasks Among other things, the agency is tasked with the following: * Drug and medical device testing: ** Scientific review of market authorization applications based on Japanese pharmaceutical law ** Advice in clinical trials or in the preparation of dossiers for the registration procedure (New Drug Applications (NDA)) ** Inspection and conformity assessment of Good Clinical Practice (GCP), Good Laboratory Practice (GLP), and Good Practice Systems and Programs (GPSP) ** Auditing of manufacturers to ensure they conform to Good Manufacturin ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
