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Acetyl-CoA
Acetyl-CoA (acetyl coenzyme A) 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 (Krebs cycle) to be oxidized for energy production. Coenzyme A (CoASH or CoA) consists of a β-mercaptoethylamine group linked to the vitamin pantothenic acid (B5) through an amide linkage and 3'-phosphorylated ADP. The acetyl group (indicated in blue in the structural diagram on the right) 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). CoA is acetylated to acetyl-CoA by the breakdown of carbohydrates through glycolysis and by the breakdown of fatty acids through β-oxidation. Acetyl-CoA then enters the citric acid cycle, where the acetyl group is oxidized to carbon dioxide and ...
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Citric Acid Cycle
The citric acid cycle (CAC)—also known as the Krebs cycle or the TCA cycle (tricarboxylic acid cycle)—is a series of chemical reactions to release stored energy through the oxidation of acetyl-CoA derived from carbohydrates, fats, and proteins. The Krebs cycle is used by organisms that respire (as opposed to organisms that ferment) to generate energy, either by anaerobic respiration or aerobic respiration. 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 alternative segments of the citric acid cycle have been recognized. The name of this metabolic pathway is derived from the citric acid (a tricarboxy ...
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Coenzyme A
Coenzyme A (CoA, SHCoA, CoASH) is a coenzyme, notable for its role in the synthesis and oxidation of fatty acids, and the oxidation of pyruvate in the citric acid cycle. All genomes sequenced to date encode enzymes that use coenzyme A as a substrate, and around 4% of cellular enzymes use it (or a thioester) as a substrate. In humans, CoA biosynthesis requires cysteine, pantothenic acid, pantothenate (vitamin B5), and adenosine triphosphate (ATP). In acetyl-CoA, its acetyl form, coenzyme A is a highly versatile molecule, serving metabolic functions in both the Anabolism, anabolic and Catabolism, catabolic pathways. Acetyl-CoA is utilised in the post-translational regulation and allosteric regulation of pyruvate dehydrogenase and carboxylase to maintain and support the partition of Pyruvic acid, pyruvate synthesis and degradation. Discovery of structure Coenzyme A was identified by Fritz Lipmann in 1946, who also later gave it its name. Its structure was determined during the e ...
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Coenzyme A
Coenzyme A (CoA, SHCoA, CoASH) is a coenzyme, notable for its role in the synthesis and oxidation of fatty acids, and the oxidation of pyruvate in the citric acid cycle. All genomes sequenced to date encode enzymes that use coenzyme A as a substrate, and around 4% of cellular enzymes use it (or a thioester) as a substrate. In humans, CoA biosynthesis requires cysteine, pantothenic acid, pantothenate (vitamin B5), and adenosine triphosphate (ATP). In acetyl-CoA, its acetyl form, coenzyme A is a highly versatile molecule, serving metabolic functions in both the Anabolism, anabolic and Catabolism, catabolic pathways. Acetyl-CoA is utilised in the post-translational regulation and allosteric regulation of pyruvate dehydrogenase and carboxylase to maintain and support the partition of Pyruvic acid, pyruvate synthesis and degradation. Discovery of structure Coenzyme A was identified by Fritz Lipmann in 1946, who also later gave it its name. Its structure was determined during the e ...
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ATP Citrate Lyase
ATP citrate synthase (also ATP citrate lyase (ACLY)) is an enzyme that in animals represents an important step in fatty acid biosynthesis. By converting citrate to acetyl-CoA, the enzyme links carbohydrate metabolism, which yields citrate as an intermediate, with fatty acid biosynthesis, which consumes acetyl-CoA. In plants, ATP citrate lyase generates cytosolic acetyl-CoA precursors of thousands of specialized metabolites, including waxes, sterols, and polyketides. Function ATP citrate lyase is the primary enzyme responsible for the synthesis of cytosolic acetyl-CoA in many tissues. The enzyme is a tetramer of apparently identical subunits. In animals, the product, acetyl-CoA, is used in several important biosynthetic pathways, including lipogenesis and cholesterogenesis. It is activated by insulin. In plants, ATP citrate lyase generates acetyl-CoA for cytosolically-synthesized metabolites; Acetyl-CoA is not transported across subcellular membranes of plants. Such metabolite ...
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Acetyl
In organic chemistry, acetyl is a functional group with the chemical formula and the structure . It is sometimes represented by the symbol Ac (not to be confused with the element actinium). In IUPAC nomenclature, acetyl is called ethanoyl, although this term is barely heard. The acetyl group contains a methyl group () single-bonded to a carbonyl (). The carbonyl center of an acyl radical has one nonbonded electron with which it forms a chemical bond to the remainder ''R'' of the molecule. The acetyl moiety is a component of many organic compounds, including acetic acid, the neurotransmitter acetylcholine, acetyl-CoA, acetylcysteine, acetaminophen (also known as paracetamol), and acetylsalicylic acid (also known as aspirin). Acetylation In nature The introduction of an acetyl group into a molecule is called acetylation. In biological organisms, acetyl groups are commonly transferred from acetyl-CoA to other organic molecules. Acetyl-CoA is an intermediate both ...
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Beta Oxidation
In biochemistry and metabolism, beta-oxidation is the catabolic process by which fatty acid molecules are broken down in the cytosol in prokaryotes and in the mitochondria in eukaryotes to generate acetyl-CoA, which enters the citric acid cycle, and NADH and FADH2, which are co-enzymes used in the electron transport chain. It is named as such because the beta carbon of the fatty acid undergoes oxidation to a carbonyl group. Beta-oxidation is primarily facilitated by the mitochondrial trifunctional protein, an enzyme complex associated with the inner mitochondrial membrane, although very long chain fatty acids are oxidized in peroxisomes. The overall reaction for one cycle of beta oxidation is: :C''n''-acyl-CoA + FAD + + + CoA → C''n''-2-acyl-CoA + + NADH + + acetyl-CoA Activation and membrane transport Free fatty acids cannot penetrate any biological membrane due to their negative charge. Free fatty acids must cross the cell membrane through specific transport pro ...
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Thioester
In organic chemistry, thioesters are organosulfur compounds with the functional group . They are analogous to carboxylate esters () with the sulfur in the thioester playing the role of the linking oxygen in the carboxylate ester, as implied by the ''thio-'' prefix. They are the product of esterification between a carboxylic acid () and a thiol (). In biochemistry, the best-known thioesters are derivatives of coenzyme A, e.g., acetyl-CoA.Matthys J. Janssen "Carboxylic Acids and Esters" in PATAI's Chemistry of Functional Groups: Carboxylic Acids and Esters, Saul Patai, Ed. John Wiley, 1969, New York: pp. 705–764. Synthesis The most typical route to thioester involves the reaction of an acid chloride with an alkali metal salt of a thiol: :RSNa + R'COCl -> R'COSR + NaCl Another common route entails the displacement of halides by the alkali metal salt of a thiocarboxylic acid. For example, thioacetate esters are commonly prepared by alkylation of potassium thioacetate: :CH3COSK + ...
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Metabolism
Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cellular processes; the conversion of food 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 word metabolism can also refer to the sum of all chemical reactions that occur in living organisms, including digestion and the transportation of substances into and between different cells, in which case the above described set of reactions within the cells is called intermediary (or intermediate) metabolism. Metabolic reactions may be categorized as ''catabolic'' – the ''breaking down'' of compounds (for example, of glucose to pyruvate by ce ...
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Pantothenic Acid
Pantothenic acid, also called vitamin B5 is a water-soluble B vitamin and therefore an essential nutrient. All animals require pantothenic acid in order to synthesize coenzyme A (CoA) – essential for fatty acid metabolism – as well as to, in general, synthesize and metabolize proteins, carbohydrates, and fats. Pantothenic acid is the combination of pantoic acid and β-alanine. Its name derives from the Greek ''pantos'', meaning "from everywhere", as minimally, at least small quantities of pantothenic acid are found in nearly every food. Human deficiency is very rare. As a dietary supplement or animal feed ingredient, the form commonly used is calcium pantothenate because of chemical stability, and hence long product shelf life, compared to sodium pantothenate or free pantothenic acid. Definition Pantothenic acid is a water-soluble vitamin, one of the B vitamins. It is synthesized from the amino acid β-alanine and pantoic acid (see biosynthesis and structure of coenzyme ...
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Feodor Lynen
Feodor Felix Konrad Lynen (; 6 April 19116 August 1979) 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. Biography Feodor Lynen was born in Munich on 6 April 1911. He started his studies at the chemistry department of Munich University in 1930 and graduated in March 1937 under Heinrich Wieland with the work: "On the Toxic Substances in Amanita". Lynen remained in Germany throughout World War II. In 1942 he became a chemistry lecturer at the Munich University. In 1947 he became an assistant professor and in 1953 a professor of biochemistry. From 1954 onwards he was director of the Max-Planck Institute for Cellular Chemistry in Munich, a position which was created for him at the instigation of two senior scientists, Otto Warburg and Otto H ...
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Nobel Prize In Physiology And Medicine
The Nobel Prize in Physiology or Medicine is awarded yearly by the Nobel Assembly at the Karolinska Institute for outstanding discoveries in physiology or medicine. The Nobel Prize is not a single prize, but five separate prizes that, according to Alfred Nobel's 1895 will, are awarded "to those who, during the preceding year, have conferred the greatest benefit to humankind". Nobel Prizes are awarded in the fields of Physics, Chemistry, Physiology or Medicine, Literature, and Peace. The Nobel Prize is presented annually on the anniversary of Alfred Nobel's death, 10 December. As of 2022, 114 Nobel Prizes in Physiology or Medicine have been awarded to 226 laureates, 214 men and 12 women. The first one was awarded in 1901 to the German physiologist, Emil von Behring, for his work on serum therapy and the development of a vaccine against diphtheria. The first woman to receive the Nobel Prize in Physiology or Medicine, Gerty Cori, received it in 1947 for her role in elucidating the ...
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Fritz Lipmann
Fritz Albert Lipmann (; June 12, 1899 – July 24, 1986) was a German-American biochemist and a co-discoverer in 1945 of coenzyme A. For this, together with other research on coenzyme A, he was awarded the Nobel Prize in Physiology or Medicine in 1953 (shared with Hans Adolf Krebs). Early life and education Lipmann was born in Königsberg, Germany, to a Jewish family. His parents were Gertrud (Lachmanski) and Leopold Lipmann, an attorney. Lipmann studied medicine at the University of Königsberg, Berlin, and Munich, graduating in Berlin in 1924. He returned to Königsberg to study chemistry under Professor Hans Meerwein. In 1926 he joined Otto Meyerhof at the Kaiser Wilhelm Institute for Biology, Dahlem, Berlin, for his doctoral thesis. After that he followed Meyerhof to Heidelberg to the Kaiser Wilhelm Institute for Medical Research. Career From 1939 on, Lipmann lived and worked in the United States. He was a Research Associate in the Department of Biochemistry, Cornell Univer ...
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