|Richard Tecwyn Williams|
|Born||February 20, 1909|
|Died||December 29, 1979 70)(aged|
|Awards||Fellow of the Royal Society|
Richard Tecwyn Williams FRS(20 February 1909 – 29 December 1979) was a Welsh biochemist who founded the systematic study of xenobiotic metabolism with the publication of his book Detoxication mechanisms in 1947. This seminal book built on his earlier work on the role of glucuronic acid in the metabolism of borneol.
Fellowship of the Royal Society is an award granted to individuals that the Royal Society of London judges to have made a 'substantial contribution to the improvement of natural knowledge, including mathematics, engineering science and medical science'.
The Welsh are a Celtic nation and ethnic group native to, or otherwise associated with, Wales, Welsh culture, Welsh history and the Welsh language. Wales is a country that is part of the United Kingdom, and the majority of people living in Wales are British citizens.
Biochemists are scientists that are trained in biochemistry.
He was born in Abertillery, Wales in 1909 and educated at the Gelli Crug Junior School and Secondary School, Abertillery. He then went on to University College, Cardiff to study chemistry and physiology and was awarded his B.Sc. degree in 1928. In 1931, he published the structure of glucuronic acid in the leading scientific journal, Nature.
Abertillery Comprehensive School is a comprehensive school in Abertillery, Wales.
In 1949 he took up the chair of biochemistry at St Mary's Hospital Medical School in London where, in the 1950s, he worked on the metabolism of thalidomide.
St Mary's is the youngest of the constituent schools of Imperial College London, founded in 1854 as part of the new hospital in Paddington. During its existence in the 1980s and 1990s, it was the most popular medical school in the country, with an application to place ratio of 27:1 in 1996.
He was elected a Fellow of the Royal Society in March 1967.His application citation read: "The researches of Williams have been largely responsible for laying the foundations of biochemical toxicology. He has worked on the metabolism of aliphatic alcohols, alicyclic hydrocarbons, benzenes and alkylbenzenes, sulphonamides, drugs of a wide variety, heterocycles, and organotin compounds. He is especially known for his work on fluorescence and his studies on thalidomide in which he has shown that none of the twelve breakdown products which he identified is teratogenic. Williams has also defined the structural factors required for a compound to be excreted through the bile. He has discovered species differences which may have an application in primate classification. His work is of immediate relevance to an understanding of drug metabolism and action and that of the biological effects of food additives, pesticides, and other compounds foreign to the body".
He died of cancer in 1979. He married Josephine Sullivan in 1937; they had five children.
Metabolism is the set of life-sustaining chemical reactions in organisms. The three main purposes of metabolism are: the conversion of food to energy to run cellular processes; the conversion of food/fuel to building blocks for proteins, lipids, nucleic acids, and some carbohydrates; and the elimination of nitrogenous wastes. These enzyme-catalyzed reactions allow organisms to grow and reproduce, maintain their structures, and respond to their environments..
Frederick Sanger was a British biochemist who twice won the Nobel Prize in Chemistry, one of only two people to have done so in the same category, the fourth person overall with two Nobel Prizes, and the third person overall with two Nobel Prizes in the sciences. In 1958, he was awarded a Nobel Prize in Chemistry "for his work on the structure of proteins, especially that of insulin". In 1980, Walter Gilbert and Sanger shared half of the chemistry prize "for their contributions concerning the determination of base sequences in nucleic acids". The other half was awarded to Paul Berg "for his fundamental studies of the biochemistry of nucleic acids, with particular regard to recombinant DNA".
Detoxification or detoxication is the physiological or medicinal removal of toxic substances from a living organism, including the human body, which is mainly carried out by the liver. Additionally, it can refer to the period of withdrawal during which an organism returns to homeostasis after long-term use of an addictive substance. In medicine, detoxification can be achieved by decontamination of poison ingestion and the use of antidotes as well as techniques such as dialysis and chelation therapy.
A xenobiotic is a chemical substance found within an organism that is not naturally produced or expected to be present within the organism. It can also cover substances that are present in much higher concentrations than are usual.
Feodor Felix Konrad Lynen was a German biochemist. In 1964 he won the Nobel Prize in Physiology or Medicine together with Konrad Bloch for their discoveries concerning the mechanism and regulation of cholesterol and fatty acid metabolism while he was director of the Max-Planck Institute for Cellular Chemistry in Munich.
Cytochrome P450 2E1 is a member of the cytochrome P450 mixed-function oxidase system, which is involved in the metabolism of xenobiotics in the body. This class of enzymes is divided up into a number of subcategories, including CYP1, CYP2, and CYP3, which as a group are largely responsible for the breakdown of foreign compounds in mammals.
Drug metabolism is the metabolic breakdown of drugs by living organisms, usually through specialized enzymatic systems. More generally, xenobiotic metabolism is the set of metabolic pathways that modify the chemical structure of xenobiotics, which are compounds foreign to an organism's normal biochemistry, such as any drug or poison. These pathways are a form of biotransformation present in all major groups of organisms, and are considered to be of ancient origin. These reactions often act to detoxify poisonous compounds. The study of drug metabolism is called pharmacokinetics.
A glucuronide, also known as glucuronoside, is any substance produced by linking glucuronic acid to another substance via a glycosidic bond. The glucuronides belong to the glycosides.
Glucuronidation is often involved in drug metabolism of substances such as drugs, pollutants, bilirubin, androgens, estrogens, mineralocorticoids, glucocorticoids, fatty acid derivatives, retinoids, and bile acids. These linkages involve glycosidic bonds.
Glucuronic acid is a uronic acid that was first isolated from urine. It is found in many gums such as gum arabic and xanthan, and is important for the metabolism of microorganisms, plants and animals.
Phenylacetone is an organic compound with the chemical formula C6H5CH2COCH3. It is a colorless oil that is soluble in organic solvents. This substance is used in the manufacture of methamphetamine and amphetamine, where it is commonly known as P2P. Due to the illicit uses in clandestine chemistry, it was declared a schedule II controlled substance in the United States in 1980. In humans, phenylacetone occurs as a metabolite of amphetamine and methamphetamine via FMO3-mediated oxidative deamination.
Uridine 5'-diphospho-glucuronosyltransferase is a cytosolic glycosyltransferase that catalyzes the transfer of the glucuronic acid component of UDP-glucuronic acid to a small hydrophobic molecule. This is a glucuronidation reaction.
Cytochrome P450, family 1, subfamily A, polypeptide 1 is a protein that in humans is encoded by the CYP1A1 gene. The protein is a member of the cytochrome P450 superfamily of enzymes.
In the field of molecular biology, the pregnane X receptor (PXR), also known as the steroid and xenobiotic sensing nuclear receptor (SXR) or nuclear receptor subfamily 1, group I, member 2 (NR1I2) is a protein that in humans is encoded by the NR1I2 gene.
UGT2B7 (UDP-Glucuronosyltransferase-2B7) is a phase II metabolism isoenzyme found to be active in the liver, kidneys, epithelial cells of the lower gastrointestinal tract and also has been reported in the brain. In humans, UDP-Glucuronosyltransferase-2B7 is encoded by the UGT2B7 gene.
Oswald Schmiedeberg was a Baltic German pharmacologist. He is sometimes referred to as the "Father of Modern Pharmacology."
Aldehyde oxidase (AO) is a metabolizing enzyme, located in the cytosolic compartment of tissues in many organisms. AO catalyzes the oxidation of aldehydes into carboxylic acid, and in addition, catalyzes the hydroxylation of some heterocycles. It can also catalyze the oxidation of both cytochrome P450 (CYP450) and monoamine oxidase (MAO) intermediate products. AO plays a very important role in the metabolization of numerous drugs.
Biotransformation is the chemical modification (or modifications) made by an organism on a chemical compound. If this modification ends in mineral compounds like CO2, NH4+, or H2O, the biotransformation is called mineralisation.
p-Hydroxynorephedrine, or 4-hydroxynorephedrine, is the para-hydroxy analog of norephedrine and an active sympathomimetic metabolite of amphetamine in humans. When it occurs as a metabolite of amphetamine, it is produced from both p-hydroxyamphetamine and norephedrine.
The flavin-containing monooxygenase (FMO) protein family specializes in the oxidation of xeno-substrates in order to facilitate the excretion of these compounds from living organisms. These enzymes can oxidize a wide array of heteroatoms, particularly soft nucleophiles, such as amines, sulfides, and phosphites. This reaction requires an oxygen, an NADPH cofactor, and an FAD prosthetic group. FMOs share several structural features, such as a NADPH binding domain, FAD binding domain, and a conserved arginine residue present in the active site. Recently, FMO enzymes have received a great deal of attention from the pharmaceutical industry both as a drug target for various diseases and as a means to metabolize pro-drug compounds into active pharmaceuticals. These monooxygenases are often misclassified because they share activity profiles similar to those of cytochrome P450 (CYP450), which is the major contributor to oxidative xenobiotic metabolism. However, a key difference between the two enzymes lies in how they proceed to oxidize their respective substrates; CYP enzymes make use of an oxygenated heme prosthetic group, while the FMO family utilizes FAD to oxidize its substrates.
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