Sir Hans Adolf Krebs
|Died||22 November 1981 81) (aged|
|Citizenship||Naturalised British (from 1939)|
|Alma mater|| University of Göttingen |
University of Freiburg
University of Berlin
University of Hamburg
|Known for|| Citric acid cycle |
Margaret Cicely Fieldhouse
|Children||Paul, John, and Helen|
|Awards|| Albert Lasker Award for Basic Medical Research (1953)|
Nobel Prize in Physiology or Medicine (1953)
Royal Medal (1954)
Copley Medal (1961)
|Fields||Internal medicine, biochemistry|
|Institutions|| Kaiser Wilhelm Institute for Biology |
University of Hamburg
University of Cambridge
University of Sheffield
University of Oxford
Sir Hans Adolf Krebs ( /, / ; 25 August 1900 – 22 November 1981) was a German-born British biologist, physician and biochemist. He was a pioneer scientist in the study of cellular respiration, a biochemical process in living cells that extracts energy from food and oxygen and makes it available to drive the processes of life. He is best known for his discoveries of two important sequences of chemical reactions that take place in the cells of humans and many other organisms, namely the citric acid cycle and the urea cycle. The former, often eponymously known as the "Krebs cycle", is the key sequence of metabolic reactions that provides energy in the cells of humans and other oxygen-respiring organisms; and its discovery earned Krebs a Nobel Prize in Physiology or Medicine in 1953. With Hans Kornberg, he also discovered the glyoxylate cycle, which is a slight variation of the citric acid cycle found in plants, bacteria, protists, and fungi. Krebs died in 1981 in Oxford, where he had spent 13 years of his career from 1954 until his retirement in 1967 at the University of Oxford.
Krebs was born in Hildesheim, Germany, to Georg Krebs, an ear, nose, and throat surgeon, and Alma Krebs (née Davidson). He descended from Jewish-Silesian ancestry and was the middle of three children, older sister Elisabeth and younger brother Wolfgang.
Krebs attended the famous old Gymnasium Andreanum in his home town. Near the end of World War I, in September 1918, six months short of completing his secondary school education, he was conscripted into the Imperial German Army. He was allowed to take an emergency examination for his high school diploma, which he passed with such a high score that he suspected the examiners of being "unduly lenient and sympathetic".With the end of the war two months later, his conscription ended.
Krebs decided to follow his father's profession and entered the University of Göttingen in December 1918 to study medicine. In 1919 he transferred to the University of Freiburg. In 1923 he published his first scientific paper on a tissue staining technique. He did this work under the guidance of Wilhelm von Mollendorf starting it in 1920. He completed his medical course in December 1923. To obtain a Doctor of Medicine degree, and a medical license, he spent one year at the Third Medical Clinic in the University of Berlin. By then he had turned his professional goal from becoming a practising physician to becoming a medical researcher, particularly in biochemistry. In 1924 he studied at the Department of Chemistry at the Pathological Institute of the Charité Hospital, in Berlin, for training in chemistry and biochemistry. He earned his MD degree in 1925 from the University of Hamburg.
In 1926 Krebs joined Otto Heinrich Warburg as a research assistant at the Kaiser Wilhelm Institute for Biology in Dahlem, Berlin. He was paid a modest 4800 marks per year. After four years in 1930, with 16 publications to his credit, his mentor Warburg urged him to move on and he took up the position of Assistant in the Department of Medicine at the Municipal Hospital in Altona (now part of Hamburg). The next year he moved to the Medical Clinic of the University of Freiburg. At Freiburg he was in charge of about 40 patients, and was at liberty to do his own research. Before a year was over at Freiburg, he, with research student Kurt Henseleit, published their discovery of the ornithine cycle of urea synthesis, which is the metabolic pathway for urea formation. It is now known as the urea cycle, and is sometimes also referred to as the Krebs–Henseleit cycle. Together they also developed a complex aqueous solution (a buffer), or perfusion ex vivo, for studying blood flow in arteries, which is now called the Krebs–Henseleit buffer.)In 1932 he published the basic chemical reactions of the urea cycle, which established his scientific reputation.
Krebs's life as a respected German scientist came to an abrupt halt in 1933 because of his Jewish ancestry. With the rise of Hitler's Nazi Party to power, Germany decreed the Law for the Restoration of the Professional Civil Service, which decreed the removal of all non-Germans, and anti-Nazis, from professional occupations. Krebs received his official dismissal from his job in April 1933, and his service was terminated on 1 July 1933. An admirer, Sir Frederick Gowland Hopkins at the University of Cambridge, immediately came to his rescue, and persuaded the university to recruit Krebs to work with him in the Department of Biochemistry.By July 1933 he was settled in Cambridge with financial support from the Rockefeller Foundation. Although Germany restricted him to bringing only his personal belongings, he was fortunate that the government agents allowed him to take his equipment and research samples to England. They proved to be pivotal to his later discoveries, especially the manometer developed by Warburg specifically for the measurement of oxygen consumption in thin slices of tissues; it was the basis for his research. He was appointed as Demonstrator in biochemistry in 1934 and in 1935 the University of Sheffield offered him a post of Lecturer in Pharmacology, with a more spacious laboratory and double the salary. He worked there for 19 years. University of Sheffield opened a Department of Biochemistry, now Department of Molecular Biology and Biotechnology, in 1938 and Krebs became its first Head, and eventually a Professor in 1945. Krebs took over the running of the Sorby Research Institute in 1943. In 1944, the British Medical Research Council established the MRC Unit for Cell Metabolism Research at Sheffield, and Krebs was appointed the Director. With this his laboratory became so large that the locals jokingly nicknamed it "Krebs's Empire". He moved with his MRC unit to the University of Oxford in 1954 as Whitley Professor of Biochemistry, the post he held till his retirement in 1967. The editorial board of Biochemical Journal extended their good wishes on his retirement, but in return he promised to keep them busy, by producing scientific papers. He continued his research, and took his MRC unit to the Nuffield Department of Clinical Medicine at the Radcliffe Infirmary, Oxford. From there he published over 100 research papers.
Krebs met Margaret Cicely Fieldhouse (30 October 1913 – May 1993)when he moved to Sheffield in 1935. They married on 22 March 1938. Krebs later described his life in Sheffield as "19 happy years". They had two sons, Paul (born 1939) and John (born 1945), and a daughter, Helen (born 1942). John (Sir John Krebs, and later Baron Krebs) became a renowned ornithologist, Professor at the University of Oxford, Principal of Jesus College, Oxford, and Member of the British House of Lords.
After a brief illness, Krebs died on 22 November 1981 in Oxford.
In 1932 Krebs worked out the outlines of the urea cycle with a medical student Kurt Henseleit at the university of Freiburg. While working at the Medical Clinic of the University of Freiburg, Krebs met Kurt Henseleit, with whom he investigated the chemical process of urea formation. In 1904, two Germans A. Kossel and H. D. Dakin had shown that arginine could be hydrolysed by the enzyme arginase to form ornithine and urea in inorganic reaction.Based on this reaction, Krebs and Henseleit postulated that in living cells, similar reaction could occur, and that ornithine and citrulline could be the intermediate reactions. Krebs started working on the possible method for the synthesis of arginine. Using his Warburg manometer, he mixed a slice of liver with purified ornithine and citrulline. He found that citrulline acted as a catalyst in the metabolic reactions of urea from ammonia and carbon dioxide. He and Henseleit published their discovery in 1932. Thus the urea cycle (or "ornithine cycle") was established, and it was the first metabolic cycle to be discovered.
At the University of Sheffield, Krebs and William Johnson investigated cellular respiration by which oxygen was consumed to produce energy from the breakdown of glucose. Krebs had earlier suggested to Warburg while they worked together in Germany that by using a manometer it could be possible to detect the oxygen consumption and identify the chemical reaction in glucose metabolism. Warburg had flatly rejected the idea. In Sheffield Krebs vigorously worked to identify a possible chemical reaction and came up with numerous hypothetical pathways. Using the manometer he tested those hypotheses one by one. One hypothesis involving succinate, fumarate, and malate proved to be useful because all these molecules increased oxygen consumption in the pigeon breast muscle. In 1937 German biochemists Franz Koop and Carl Martinus had demonstrated a series of reactions using citrate that produced oxaloacetate. Krebs realised that these molecules could be the missing intermediates for such reaction. After four months of experimental works to fill in the gaps, Krebs and Johnson succeeded in establishing the sequence of the chemical cycle, which they called the "citric acid cycle".It is also known as the "Krebs cycle" or "tricarboxylic acid (TCA) cycle".
Krebs sent a short manuscript account of the discovery to Nature on 10 June 1937. On 14 June he received a rejection letter from the editor, saying that the journal had "already sufficient letters to fill correspondence columns for seven or eight weeks", and encouraging Krebs to "submit it for early publication to another periodical."Krebs immediately prepared a longer version titled "The Role of Citric Acid in Intermediate Metabolism in Animal Tissues", which he sent to the Dutch journal Enzymologia after two weeks and was published in two months. It was followed by a series of papers in different journals.
Krebs continued to add more details to his citric acid cycle. The discovery of acetyl-CoA in 1947 by Fritz Albert Lipmann was another major contribution.However, this new discovery posed a problem in his classic reaction. In 1957 he, with Hans Kornberg, found that there were additional crucial enzymes. One was malate synthase, which condenses acetate with glyoxylate to form malate, and the other was isocitrate lyase, which provides glyoxylate for the reaction by cleaving it from isocitrate. These two reactions did not follow the normal citric acid cycle, and hence the pathway was named the glyoxylate bypass of the citric acid cycle, but is now known as the glyoxylate cycle.
Krebs became a naturalised British citizen in 1939. He was elected Fellow of Trinity College, Oxford, 1954–1967. He was elected to the Royal Society in 1947. In 1953 he received the Nobel Prize in Physiology or Medicine for his "discovery of the citric acid cycle." (He shared the Nobel Prize with Fritz Lipmann.) For the same reason he was given the Albert Lasker Award for Basic Medical Research in 1953.The Royal Society awarded him its Royal Medal in 1954, and Copley Medal in 1961. In 1958 he received the Gold Medal of the Netherlands Society for Physics, Medical Science and Surgery. He was knighted in 1958 and was elected Honorary Fellow of Girton College, Cambridge University in 1979. He was the Original Member of the Society for General Microbiology, which conferred him Honorary Membership in 1980. He received an honorary doctorate from 21 universities.
In July 2015, Krebs's Nobel Prize medal was auctioned off for £225,000 (around $351,225).The proceeds were used to found the Sir Hans Krebs Trust, which provides funding for doctoral students in the biomedical field and support chemists who had to flee their home countries.
The University of Oxford had a building named Hans Krebs Tower, which was occupied by the Department of Biochemistry. In 2008 a new building for the Department of Biochemistry was constructed, on which a plaque was placed on 20 May 2013 by the Association of Jewish Refugees.The plaque was unveiled by John, Lord Krebs, and the inscription reads:
Professor Sir Hans Krebs FRS 1900 – 1981 Biochemist & discoverer of the Krebs cycle Nobel Prize Winner 1953 worked here 1954 – 1967
The University of Sheffield has The Krebs Institute, founded in 1988. It is a research centre covering interdisciplinary programmes in biochemical research.
In 1990 the Federation of European Biochemical Societies instituted the Sir Hans Krebs Lecture and Medal, which was endowed by the Lord Rank Centre for Research. It is awarded for outstanding achievements in biochemistry and molecular biology.
The Society of Friends of Hannover Medical School gives the Sir Hans Krebs Prize, which is worth 10,000 euros.
The Biochemical Society offers Krebs Memorial Scholarship to a postgraduate (PhD) student working in biochemistry or an allied biomedical science at any British university. As of 2014, the scholarship is worth £18,500 and is given for a year, but is extendable up to three years.
Biochemistry, sometimes called biological chemistry, is the study of chemical processes within and relating to living organisms. Biochemical processes give rise to the complexity of life.
The citric acid cycle (CAC) – also known as the TCA cycle or the Krebs cycle – is a series of chemical reactions used by all aerobic organisms to release stored energy through the oxidation of acetyl-CoA derived from carbohydrates, fats, and proteins. In addition, the cycle provides precursors of certain amino acids, as well as the reducing agent NADH, that are used in numerous other reactions. Its central importance to many biochemical pathways suggests that it was one of the earliest components of metabolism and may have originated abiogenically. Even though it is branded as a 'cycle', it is not necessary for metabolites to follow only one specific route; at least three segments of the citric acid cycle have been recognized.
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 metabolic wastes. These enzyme-catalyzed reactions allow organisms to grow and reproduce, maintain their structures, and respond to their environments..
The urea cycle (also known as the ornithine cycle) is a cycle of biochemical reactions that produces urea (NH2)2CO from ammonia (NH3). This cycle occurs in ureotelic organisms. The urea cycle converts highly toxic ammonia to urea for excretion. This cycle was the first metabolic cycle to be discovered (Hans Krebs and Kurt Henseleit, 1932), five years before the discovery of the TCA cycle. This cycle was described in more detail later on by Ratner and Cohen. The urea cycle takes place primarily in the liver and, to a lesser extent, in the kidneys.
Pyruvic acid (CH3COCOOH) is the simplest of the alpha-keto acids, with a carboxylic acid and a ketone functional group. Pyruvate, the conjugate base, CH3COCOO−, is a key intermediate in several metabolic pathways throughout the cell.
Acetyl-CoA is a molecule that participates in many biochemical reactions in protein, carbohydrate and lipid metabolism. Its main function is to deliver the acetyl group to the citric acid cycle to be oxidized for energy production. Coenzyme A consists of a β-mercaptoethylamine group linked to the vitamin pantothenic acid (B5) through an amide linkage and 3'-phosphorylated ADP. The acetyl group of acetyl-CoA is linked to the sulfhydryl substituent of the β-mercaptoethylamine group. This thioester linkage is a "high energy" bond, which is particularly reactive. Hydrolysis of the thioester bond is exergonic (−31.5 kJ/mol).
Otto Heinrich Warburg, son of physicist Emil Warburg, was a German physiologist, medical doctor, and Nobel laureate. He served as an officer in the elite Uhlan during the First World War, and was awarded the Iron Cross for bravery. He was the sole recipient of the Nobel Prize in Physiology or Medicine in 1931. In total, he was nominated for the award 47 times over the course of his career.
Arginase (EC 126.96.36.199, arginine amidinase, canavanase, L-arginase, arginine transamidinase) is a manganese-containing enzyme. The reaction catalyzed by this enzyme is: arginine + H2O → ornithine + urea. It is the final enzyme of the urea cycle. It is ubiquitous to all domains of life.
Oxaloacetic acid (also known as oxalacetic acid) is a crystalline organic compound with the chemical formula HO2CC(O)CH2CO2H. Oxaloacetic acid, in the form of its conjugate base oxaloacetate, is a metabolic intermediate in many processes that occur in animals. It takes part in gluconeogenesis, the urea cycle, the glyoxylate cycle, amino acid synthesis, fatty acid synthesis and the citric acid cycle.
Peter Dennis Mitchell, FRS was a British biochemist who was awarded the 1978 Nobel Prize for Chemistry for his discovery of the chemiosmotic mechanism of ATP synthesis.
In the mitochondrion, the matrix is the space within the inner membrane. The word "matrix" stems from the fact that this space is viscous, compared to the relatively aqueous cytoplasm. The mitochondrial matrix contains the mitochondria's DNA, ribosomes, soluble enzymes, small organic molecules, nucleotide cofactors, and inorganic ions. The enzymes in the matrix facilitate reactions responsible for the production of ATP, such as the citric acid cycle, oxidative phosphorylation, oxidation of pyruvate, and the beta oxidation of fatty acids.
Edwin Gerhard Krebs was an American biochemist. He received the Albert Lasker Award for Basic Medical Research and the Louisa Gross Horwitz Prize of Columbia University in 1989 together with Alfred Gilman and, together with his collaborator Edmond H. Fischer, was awarded the Nobel Prize in Physiology or Medicine in 1992 for describing how reversible phosphorylation works as a switch to activate proteins and regulate various cellular processes.
The glyoxylate cycle, a variation of the tricarboxylic acid cycle, is an anabolic pathway occurring in plants, bacteria, protists, and fungi. The glyoxylate cycle centers on the conversion of acetyl-CoA to succinate for the synthesis of carbohydrates. In microorganisms, the glyoxylate cycle allows cells to utilize two carbons, such as acetate, to satisfy cellular carbon requirements when simple sugars such as glucose or fructose are not available. The cycle is generally assumed to be absent in animals, with the exception of nematodes at the early stages of embryogenesis. In recent years, however, the detection of malate synthase (MS) and isocitrate lyase (ICL), key enzymes involved in the glyoxylate cycle, in some animal tissue has raised questions regarding the evolutionary relationship of enzymes in bacteria and animals and suggests that animals encode alternative enzymes of the cycle that differ in function from known MS and ICL in non-metazoan species.
Sir Hans Leo Kornberg, FRS was a British-American biochemist. He was Sir William Dunn Professor of Biochemistry in the University of Cambridge from 1975 to 1995, and Master of Christ's College, Cambridge from 1982 to 1995.
N-Acetylglutamate synthase (NAGS) is an enzyme that catalyses the production of N-acetylglutamate (NAG) from glutamate and acetyl-CoA.
Norman Lowther Edson, FRSNZ, FNZIC, was the first Professor of Biochemistry (1949–1967) in the University of New Zealand based at the University of Otago, Dunedin, New Zealand where he founded a department of biochemistry. Edson made contributions to the understanding of, ketone body metabolism in mammals and birds, metabolic pathways of Mycobacteria and specificity rules for polyol dehydrogenases.
The Department of Biochemistry of Oxford University is located in the Science Area in Oxford, England. It is one of the largest biochemistry departments in Europe. The Biochemistry Department is part of the University of Oxford's Medical Sciences Division, the largest of the University's four academic divisions, which has been ranked first in the world for biomedicine.
The history of biochemistry can be said to have started with the ancient Greeks who were interested in the composition and processes of life, although biochemistry as a specific scientific discipline has its beginning around the early 19th century. Some argued that the beginning of biochemistry may have been the discovery of the first enzyme, diastase, in 1833 by Anselme Payen, while others considered Eduard Buchner's first demonstration of a complex biochemical process alcoholic fermentation in cell-free extracts to be the birth of biochemistry. Some might also point to the influential work of Justus von Liebig from 1842, Animal chemistry, or, Organic chemistry in its applications to physiology and pathology, which presented a chemical theory of metabolism, or even earlier to the 18th century studies on fermentation and respiration by Antoine Lavoisier.
In enzymology, a malate synthase (EC 188.8.131.52) is an enzyme that catalyzes the chemical reaction
The Sir Hans Krebs Lecture and Medal is awarded annually by the Federation of European Biochemical Societies (FEBS) for outstanding achievements in Biochemistry and Molecular Biology or related sciences.