BROWN (Brown), Michael( The American geneticist, Nobel Prize in Physiology or Medicine, 1985)
Comments for BROWN (Brown), Michael
Biography BROWN (Brown), Michael
genus. April 13, 1941
American geneticist, Michael Stuart Brown was born in New York, the son of Harvey Brown and Evelyn Brown (Katz). He studied at the University of Pennsylvania, where he studied chemistry and worked in the university newspaper. In 1962. he received at this university bachelor's degree, and in 1966. - The degree of Doctor of Medicine. In the next two years B. worked as a medical intern at Massachusetts General Hospital in Boston. Here he became acquainted with Joseph Goldstein, who also worked as a doctor.
In 1968. B. graduated and began working as an intern assistant professor in the department of hereditary diseases and diseases of the digestive system of the National Institute of arthritis and metabolic diseases. Here he studied the metabolism of glutamine in the laboratory of biochemistry. In 1971, Mr.. B. became an assistant professor of medicine at Southwestern Medical School, University of Texas at Dallas. The following year he was joined by Goldstein, and researchers began to study cholesterol metabolism, in particular in hereditary familial hypercholesterolemia.
. Cholesterol - a substance from the group of sterols, available in the cell membranes of all mammals
. In addition, it is a precursor of bile acids and steroid hormones. Cholesterol is synthesized in the body, and also comes with food and tolerated the blood and lymph in the form of low density lipoprotein (LDL) - large spherical particles with a core of cholesterol esters and a shell of phospholipids and free cholesterol. Due to this hydrophilic (able to connect to water) shell LDL particles are soluble in the blood. In the outer envelope also contained a large protein - apoprotein B-100. When cholesterol accumulates in excessive amounts in the walls of blood vessels, it can block the blood flow, which leads to heart attack and stroke.
. Familial hypercholesterolemia - a genetic disorder inherited in autosomal dominant and characterized by extremely high levels of blood cholesterol and LDL and the deposition of cholesterol in the tissues
. In heterozygous patients (carriers of only one gene that causes the disease) aged between 30 and 40 years of developing coronary heart disease. Ill predominantly male. Heterozygous form hypercholesterolemia in America and Europe met at one of 500 men and 85% of patients by 60 years witnessed the development of myocardial infarction. More severe homozygous form, due to the presence of two mutant genes, occurs in one of a million people, and in her heart attacks tend to occur already in childhood.
Using the method of culturing tissue B. and Goldstein grew cells from patients with familial hypercholesterolemia, skin. In these cells, they found an unusually high level of the enzyme that determines the rate of synthesis of cholesterol. Much activity of this enzyme and lead to excess cholesterol. The researchers also showed that the cells of patients with poorly bind LDL. This led to the discovery of receptors for LDL molecules on the cell surface.
In studying the mechanisms by which receptors regulate the synthesis of LDL cholesterol. B., Goldstein and Officer Richard Anderson described how apoproteinovaya of LDL binds to a specific cell surface receptors. Turned out that there is a process called receptor mediated endocytosis. This binding complex LDL - cholesterol is in the pits of the cell membrane, which then turn into bubbles, separated from the membrane and carry the complex into the cell. It later turned out that a similar mechanism and provides insight into the cell of other large molecules - insulin, iron, vitamin B12, growth factors, transferrin, and immune complexes
. In the cell disintegrate and release LDL cholesterol, under the influence of which decreases the activity of the enzyme responsible for the synthesis of new cholesterol, and increases the activity of another enzyme, providing the deposit of the substance
. Increased amounts of cholesterol in the cell also leads to inhibition of the formation of new LDL receptors. Thus, in normal cells possess a mechanism to ensure a balance between the absorption of cholesterol from food and the synthesis of this substance in the cells.
In 1984. using methods of molecular cloning B. and Goldstein determined the nucleotide sequence of the gene responsible for the synthesis of LDL receptors. They described several gene mutations that lead to familial hypercholesterolemia. Some of them lead to a breach of the synthesis of LDL receptors, while others - the fact that these receptors lost their ability to bind to LDL, and others - to ensure that the necessary signal to the binding of LDL to the enzyme systems of cells did not arise.
. Job B
. and Goldstein already yielded tangible clinical results. Appointment of patients heterozygous form of familial hypercholesterolemia (with a normal LDL receptor gene) of such drugs, . as kompaktin, . mevipolin etc., . may lead to an increase in the number of these receptors, . synthesized under the control of the intact gene, . and reducing LDL cholesterol and,
. However, such treatments are ineffective for patients with homozygous form, as they have generally not acting LDL receptor gene. In 1984. was an experimental liver transplant six years a child with this form of the disease, and, as might be the theory of B. and Goldstein, due to the presence of a transplanted liver receptors LDL cholesterol plummeted.
In 1985, Mr.. B. and Goldstein were awarded the Nobel Prize in Physiology or Medicine for his outstanding discoveries concerning the exchange of cholesterol and treatment of cholesterol in the blood.
In 80-ies. B. served as professor of medicine and genetics and also director of the Center of genetic diseases in South-Western Medical School, University of Texas. In addition, he was a member of the Scientific Council of Clinical Foundation, Jane Coffin and consultant in the trust Lucille Marks. He was a member of the editorial board of the journals 'Atherosclerosis' ( 'Atheriosclerosis') and 'Science' ( 'Science'). B. - By more than 200 scientific articles and chapters in textbooks and co-editor of Labor 'metabolic basis of inherited diseases' ( 'The Metabolic Basis of Inherited Disease').
In 1964, Mr.. B. married Alice Lapen. In the family they have two daughters. B. - An avid sailor and lover of pop music.
B. with Pfitserovskoy Goldstein won awards in the field of chemistry of enzymes of the American Chemical Society (1976), . Awards Launsberi National Academy of Sciences (1979), . international award Gardner Fund (1981), . Mattia Award of the Institute of Molecular Biology (1984) and Louise Gross Prize-Horvitz of Columbia University (1984),
. He is a member of the National Academy of Sciences, the American Academy of Arts and Sciences. American Biochemical Society and the Association of American Physicians.