Fritz Albert Lipmann
Fritz Albert Lipmann 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. Lipmann was born in Germany, to a Jewish family, his parents were Leopold Lipmann, an attorney. Lipmann studied medicine at the University of Königsberg 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 his Ph. D. thesis. After that he followed Meyerhof to Heidelberg to the Kaiser Wilhelm Institute for Medical Research. In 1931, Lipmann married Elfreda M. Hall, they had Steven. From 1939 on, Lipmann worked in the United States, he was a Research Associate in the Department of Biochemistry, Cornell University Medical College, New York from 1939 to 1941. He joined the research staff of the Massachusetts General Hospital in Boston in 1941, first as a Research Associate in the Department of Surgery heading his own group in the Biochemical Research Laboratory of the Hospital.
From 1949 to 1957 he was professor of biological chemistry at Harvard Medical School. From 1957 onwards, he conducted research at Rockefeller University, New York City, he was awarded the National Medal of Science in 1966. He died in New York in 1986, his widow Freda died in 2008 aged 101. List of Jewish Nobel laureates Hans Adolf Krebs Nobel Prize biography jewish virtual library biography Leibniz Institute for Age Research – Fritz Lipmann Institute National Academy of Sciences Biographical Memoir
Glycolysis is the metabolic pathway that converts glucose C6H12O6, into pyruvate, CH3COCOO− + H+. The free energy released in this process is used to form the high-energy molecules ATP and NADH. Glycolysis is a sequence of ten enzyme-catalyzed reactions. Most monosaccharides, such as fructose and galactose, can be converted to one of these intermediates; the intermediates may be directly useful. For example, the intermediate dihydroxyacetone phosphate is a source of the glycerol that combines with fatty acids to form fat. Glycolysis is an oxygen-independent metabolic pathway; the wide occurrence of glycolysis indicates. Indeed, the reactions that constitute glycolysis and its parallel pathway, the pentose phosphate pathway, occur metal-catalyzed under the oxygen-free conditions of the Archean oceans in the absence of enzymes. In most organisms, glycolysis occurs in the cytosol; the most common type of glycolysis is the Embden–Meyerhof–Parnas, discovered by Gustav Embden, Otto Meyerhof, Jakub Karol Parnas.
Glycolysis refers to other pathways, such as the Entner–Doudoroff pathway and various heterofermentative and homofermentative pathways. However, the discussion here will be limited to the Embden–Meyerhof–Parnas pathway; the glycolysis pathway can be separated into two phases: The Preparatory/Investment Phase – wherein ATP is consumed. The Pay Off Phase – wherein ATP is produced; the overall reaction of glycolysis is: The use of symbols in this equation makes it appear unbalanced with respect to oxygen atoms, hydrogen atoms, charges. Atom balance is maintained by the two phosphate groups: Each exists in the form of a hydrogen phosphate anion, dissociating to contribute 2 H+ overall Each liberates an oxygen atom when it binds to an ADP molecule, contributing 2 O overallCharges are balanced by the difference between ADP and ATP. In the cellular environment, all three hydroxyl groups of ADP dissociate into −O− and H+, giving ADP3−, this ion tends to exist in an ionic bond with Mg2+, giving ADPMg−.
ATP behaves identically except that it has four hydroxyl groups, giving ATPMg2−. When these differences along with the true charges on the two phosphate groups are considered together, the net charges of −4 on each side are balanced. For simple fermentations, the metabolism of one molecule of glucose to two molecules of pyruvate has a net yield of two molecules of ATP. Most cells will carry out further reactions to'repay' the used NAD+ and produce a final product of ethanol or lactic acid. Many bacteria use inorganic compounds as hydrogen acceptors to regenerate the NAD+. Cells performing aerobic respiration synthesize much more ATP, but not as part of glycolysis; these further aerobic reactions use pyruvate and NADH + H+ from glycolysis. Eukaryotic aerobic respiration produces 34 additional molecules of ATP for each glucose molecule, however most of these are produced by a vastly different mechanism to the substrate-level phosphorylation in glycolysis; the lower-energy production, per glucose, of anaerobic respiration relative to aerobic respiration, results in greater flux through the pathway under hypoxic conditions, unless alternative sources of anaerobically oxidizable substrates, such as fatty acids, are found.
The pathway of glycolysis as it is known today took 100 years to discover. The combined results of many smaller experiments were required in order to understand the pathway as a whole; the first steps in understanding glycolysis began in the nineteenth century with the wine industry. For economic reasons, the French wine industry sought to investigate why wine sometime turned distasteful, instead of fermenting into alcohol. French scientist Louis Pasteur researched this issue during the 1850s, the results of his experiments began the long road to elucidating the pathway of glycolysis, his experiments showed. While Pasteur's experiments were groundbreaking, insight into the component steps of glycolysis were provided by the non-cellular fermentation experiments of Eduard Buchner during the 1890s. Buchner demonstrated that the conversion of glucose to ethanol was possible using a non-living extract of yeast; this experiment not only revolutionized biochemistry, but allowed scientists to analyze this pathway in a more controlled lab setting.
In a series of experiments, scientists Arthur Harden and William Young discovered more pieces of glycolysis. They discovered the regulatory effects of ATP on glucose consumption during alcohol fermentation, they shed light on the role of one compound as a glycolysis intermediate: fructose 1,6-bisphosphate. The elucidation of fructose 1,6-bisphosphate was accomplished by measuring CO2 levels when yeast juice was incubated with glucose. CO2 production increased then slowed down. Harden and Young noted that this process would restart if an inorganic phosphate was added to the mixture. Harden and Young deduced that this process produced organic phosphate esters, further experiments allowed them to extract fructose diphosphate. Arthur Harden and William Young along with Nick Sheppard determined, in a second experiment, that a heat-sensitive high-molecular-weight subcellular fraction and a heat-insensitive low-molecular-weight cytoplasm fraction are required together for fermenta
In chemistry, phosphorylation of a molecule is the attachment of a phosphoryl group. Together with its counterpart, dephosphorylation, it is critical for many cellular processes in biology. Phosphorylation is important for protein function. Many proteins are phosphorylated temporarily, as are many sugars and other molecules. Protein phosphorylation is considered the most abundant post-translational modification in eukaryotes. Phosphorylation can occur on serine and tyrosine side chains through phosphoester bond formation, on histidine and arginine through phosphoramidate bonds, on aspartic acid and glutamic acid through mixed anhydride linkages. Recent evidence confirms widespread histidine phosphorylation at both the 1 and 3 N-atoms of the imidazole ring Recent work from 2017 suggests widespread human protein phosphorylation on multiple non-canonical amino acids, including motifs containing phosphorylated histidine, glutamate and lysine in HeLa cell extracts. Due to the chemical lability of these phosphorylated residues, in marked contrast to Ser and Tyr phosphorylation, the analysis of phosphorylated histidine using standard biochemical and mass spectrometric approaches is much more challenging and special procedures and separation techniques are required for their preservation alongside classical Ser and Tyr phosphorylation.
The prominent role of protein phosphorylation in biochemistry is illustrated by the huge body of studies published on the subject. Phosphorylation of sugars is the first stage in their catabolism. Phosphorylation allows cells to accumulate sugars because the phosphate group prevents the molecules from diffusing back across their transporter. Phosphorylation of glucose is a key reaction in sugar metabolism because many sugars are first converted to glucose before they are metabolized further; the chemical equation for the conversion of D-glucose to D-glucose-6-phosphate in the first step of glycolysis is given by D-glucose + ATP → D-glucose-6-phosphate + ADPΔG° = −16.7 kJ/mol Researcher D. G. Walker of the University of Birmingham determined the presence of two specific enzymes in adult guinea pig liver, both of which catalyze the phosphorylation of glucose to glucose 6 phosphate; the two enzymes have been identified as a specific non-specific hexokinase. Hepatic cell is permeable to glucose, the initial rate of phosphorylation of glucose is the rate-limiting step in glucose metabolism by the liver and non-specific hexokinase.
The role of glucose 6-phosphate in glycogen synthase: High blood glucose concentration causes an increase in intracellular levels of glucose 6 phosphate in liver, skeletal muscle and fat tissue. And non-specific hexokinase. In liver, synthesis of glycogen is directly correlated by blood glucose concentration and in skeletal muscle and adipocytes, glucose has a minor effect on glycogen synthase. High blood glucose releases insulin, stimulating the trans location of specific glucose transporters to the cell membrane; the liver’s crucial role in controlling blood sugar concentrations by breaking down glucose into carbon dioxide and glycogen is characterized by the negative delta G value, which indicates that this is a point of regulation with. The hexokinase enzyme has a low Km, indicating a high affinity for glucose, so this initial phosphorylation can proceed when glucose levels at nanoscopic scale within the blood; the phosphorylation of glucose can be enhanced by the binding of Fructose-6-phosphate, lessened by the binding fructose-1-phosphate.
Fructose consumed in the diet is converted to F1P in the liver. This negates the action of F6P on glucokinase, which favors the forward reaction; the capacity of liver cells to phosphorylate fructose exceeds capacity to metabolize fructose-1-phosphate. Consuming excess fructose results in an imbalance in liver metabolism, which indirectly exhausts the liver cell’s supply of ATP. Allosteric activation by glucose 6 phosphate, which acts as an effector, stimulates glycogen synthase, glucose 6 phosphate may inhibit the phosphorylation of glycogen synthase by cyclic AMP-stimulated protein kinase. Phosphorylation of glucose is imperative in processes within the body. For example, phosphorylating glucose is necessary for insulin-dependent mechanistic target of rapamycin pathway activity within the heart; this further suggests a link between cardiac growth. Reversible phosphorylation of proteins is an important regulatory mechanism that occurs in both prokaryotic and eukaryotic organisms, it is estimated that 230,000, 156,000 and 40,000 phosphorylation sites exist in human and yeast, respectively.
Kinases phosphorylate proteins and phosphatases dephosphorylate proteins. Many enzymes and receptors "off" by phosphorylation and dephosphorylation. Reversible phosphorylation results in a conformational change in the structure in many enzymes and receptors, causing them to become activated or deactivated. Phosphorylation occurs on serine, threonine and histidine residues in eukaryotic proteins. Histidine phosphorylation of eukaryotic proteins appears to be much more frequent than tyrosine phos
Solvation describes the interaction of solvent with dissolved molecules. Ionized and uncharged molecules interact with solvent, the strength and nature of this interaction influence many properties of the solute, including solubility and color, as well as influencing the properties of the solvent such as the viscosity and density. In the process of solvation, ions are surrounded by a concentric shell of solvent. Solvation is the process of reorganizing solute molecules into solvation complexes. Solvation involves bond formation, hydrogen bonding, van der Waals forces. Solvation of a solute by water is called hydration. Solubility of solid compounds depends on a competition between lattice energy and solvation, including entropy effects related to changes in the solvent structure. By an IUPAC definition, solvation is an interaction of a solute with the solvent, which leads to stabilization of the solute species in the solution. In the solvated state, an ion in a solution is complexed by solvent molecules.
Solvated species can be described by coordination number, the complex stability constants. The concept of the solvation interaction can be applied to an insoluble material, for example, solvation of functional groups on a surface of ion-exchange resin. Solvation is, in concept, distinct from solubility. Solvation or dissolution is quantified by its rate. Solubility quantifies the dynamic equilibrium state achieved when the rate of dissolution equals the rate of precipitation; the consideration of the units makes the distinction clearer. The typical unit for dissolution rate is mol/s; the units for solubility express a concentration: mass per volume, etc. Solvation involves different types of intermolecular interactions: hydrogen bonding, ion-dipole interactions, van der Waals forces. Which of these forces are at play depends on the molecular structure and properties of the solvent and solute; the similarity or complementary character of these properties between solvent and solute determines how well a solute can be solvated by a particular solvent.
Solvent polarity is the most important factor in determining how well it solvates a particular solute. Polar solvents have molecular dipoles, meaning that part of the solvent molecule has more electron density than another part of the molecule; the part with more electron density will experience a partial negative charge while the part with less electron density will experience a partial positive charge. Polar solvent molecules can solvate polar solutes and ions because they can orient the appropriate charged portion of the molecule towards the solute through electrostatic attraction; this creates a solvation shell around each particle of solute. The solvent molecules in the immediate vicinity of a solute particle have a much different ordering than the rest of the solvent, this area of differently ordered solvent molecules is called the cybotactic region. Water is the most common and well-studied polar solvent, but others exist, such as ethanol, acetone and dimethyl sulfoxide. Polar solvents are found to have a high dielectric constant, although other solvent scales are used to classify solvent polarity.
Polar solvents can be used to dissolve ionic compounds such as salts. The conductivity of a solution depends on the solvation of its ions. Nonpolar solvents cannot solvate ions, ions will be found as ion pairs. Hydrogen bonding among solvent and solute molecules depends on the ability of each to accept H-bonds, donate H-bonds, or both. Solvents that can donate H-bonds are referred to as protic, while solvents that do not contain a polarized bond to a hydrogen atom and cannot donate a hydrogen bond are called aprotic. H-bond donor ability is classified on a scale. Protic solvents can solvate solutes. Solvents that can accept a hydrogen bond can solvate H-bond-donating solutes; the hydrogen bond acceptor ability of a solvent is classified on a scale. Solvents such as water can both donate and accept hydrogen bonds, making them excellent at solvating solutes that can donate or accept H-bonds; some chemical compounds experience solvatochromism, a change in color due to solvent polarity. This phenomenon illustrates.
Other solvent effects include conformational or isomeric preferences and changes in the acidity of a solute. The solvation process will be thermodynamically favored only if the overall Gibbs energy of the solution is decreased, compared to the Gibbs energy of the separated solvent and solid; this means that the change in enthalpy minus the change in entropy is a negative value, or that the Gibbs energy of the system decreases. It is important to remember, that a negative Gibbs energy indicates a spontaneous process but does not provide information about the rate of dissolution. Solvation involves multiple steps with different energy consequences. First, a cavity must form in the solvent to make space for a solute; this is both entropically and enthalpically unfavorable, as solvent ordering increases and solvent-solvent interactions decrease. Stronger interactions among solvent molecules leads to a greater ethalpic penalty for cavity formation. Next, a particle of solute must separate from the bulk.
This is enthalpically unfavorable since solute-solute interactions decrease, but when the solute particle enters the cavity, the resulting solvent-solute interaction
International Standard Serial Number
An International Standard Serial Number is an eight-digit serial number used to uniquely identify a serial publication, such as a magazine. The ISSN is helpful in distinguishing between serials with the same title. ISSN are used in ordering, interlibrary loans, other practices in connection with serial literature; the ISSN system was first drafted as an International Organization for Standardization international standard in 1971 and published as ISO 3297 in 1975. ISO subcommittee TC 46/SC 9 is responsible for maintaining the standard; when a serial with the same content is published in more than one media type, a different ISSN is assigned to each media type. For example, many serials are published both in electronic media; the ISSN system refers to these types as electronic ISSN, respectively. Conversely, as defined in ISO 3297:2007, every serial in the ISSN system is assigned a linking ISSN the same as the ISSN assigned to the serial in its first published medium, which links together all ISSNs assigned to the serial in every medium.
The format of the ISSN is an eight digit code, divided by a hyphen into two four-digit numbers. As an integer number, it can be represented by the first seven digits; the last code digit, which may be 0-9 or an X, is a check digit. Formally, the general form of the ISSN code can be expressed as follows: NNNN-NNNC where N is in the set, a digit character, C is in; the ISSN of the journal Hearing Research, for example, is 0378-5955, where the final 5 is the check digit, C=5. To calculate the check digit, the following algorithm may be used: Calculate the sum of the first seven digits of the ISSN multiplied by its position in the number, counting from the right—that is, 8, 7, 6, 5, 4, 3, 2, respectively: 0 ⋅ 8 + 3 ⋅ 7 + 7 ⋅ 6 + 8 ⋅ 5 + 5 ⋅ 4 + 9 ⋅ 3 + 5 ⋅ 2 = 0 + 21 + 42 + 40 + 20 + 27 + 10 = 160 The modulus 11 of this sum is calculated. For calculations, an upper case X in the check digit position indicates a check digit of 10. To confirm the check digit, calculate the sum of all eight digits of the ISSN multiplied by its position in the number, counting from the right.
The modulus 11 of the sum must be 0. There is an online ISSN checker. ISSN codes are assigned by a network of ISSN National Centres located at national libraries and coordinated by the ISSN International Centre based in Paris; the International Centre is an intergovernmental organization created in 1974 through an agreement between UNESCO and the French government. The International Centre maintains a database of all ISSNs assigned worldwide, the ISDS Register otherwise known as the ISSN Register. At the end of 2016, the ISSN Register contained records for 1,943,572 items. ISSN and ISBN codes are similar in concept. An ISBN might be assigned for particular issues of a serial, in addition to the ISSN code for the serial as a whole. An ISSN, unlike the ISBN code, is an anonymous identifier associated with a serial title, containing no information as to the publisher or its location. For this reason a new ISSN is assigned to a serial each time it undergoes a major title change. Since the ISSN applies to an entire serial a new identifier, the Serial Item and Contribution Identifier, was built on top of it to allow references to specific volumes, articles, or other identifiable components.
Separate ISSNs are needed for serials in different media. Thus, the print and electronic media versions of a serial need separate ISSNs. A CD-ROM version and a web version of a serial require different ISSNs since two different media are involved. However, the same ISSN can be used for different file formats of the same online serial; this "media-oriented identification" of serials made sense in the 1970s. In the 1990s and onward, with personal computers, better screens, the Web, it makes sense to consider only content, independent of media; this "content-oriented identification" of serials was a repressed demand during a decade, but no ISSN update or initiative occurred. A natural extension for ISSN, the unique-identification of the articles in the serials, was the main demand application. An alternative serials' contents model arrived with the indecs Content Model and its application, the digital object identifier, as ISSN-independent initiative, consolidated in the 2000s. Only in 2007, ISSN-L was defined in the
Hydrolysis is a term used for both an electro-chemical process and a biological one. The hydrolysis of water is the separation of water molecules into hydrogen and oxygen atoms using electricity. Biological hydrolysis is the cleavage of biomolecules where a water molecule is consumed to effect the separation of a larger molecule into component parts; when a carbohydrate is broken into its component sugar molecules by hydrolysis, this is termed saccharification. Hydrolysis or saccharification is a step in the degradation of a substance. Hydrolysis can be the reverse of a condensation reaction in which two molecules join together into a larger one and eject a water molecule, thus hydrolysis adds water to break down, whereas condensation builds up by removing water and any other solvents. Some hydration reactions are hydrolysis. Hydrolysis is a chemical process in which a molecule of water is added to a substance. Sometimes this addition causes both water molecule to split into two parts. In such reactions, one fragment of the target molecule gains a hydrogen ion.
It breaks a chemical bond in the compound. A common kind of hydrolysis occurs when a salt of weak base is dissolved in water. Water spontaneously ionizes into hydroxide anions and hydronium cations; the salt dissociates into its constituent anions and cations. For example, sodium acetate dissociates in water into acetate ions. Sodium ions react little with the hydroxide ions whereas the acetate ions combine with hydronium ions to produce acetic acid. In this case the net result is a relative excess of hydroxide ions. Strong acids undergo hydrolysis. For example, dissolving sulfuric acid in water is accompanied by hydrolysis to give hydronium and bisulfate, the sulfuric acid's conjugate base. For a more technical discussion of what occurs during such a hydrolysis, see Brønsted–Lowry acid–base theory. Acid–base-catalysed hydrolyses are common, their hydrolysis occurs when the nucleophile attacks the carbon of the carbonyl group of the ester or amide. In an aqueous base, hydroxyl ions are better nucleophiles than polar molecules such as water.
In acids, the carbonyl group becomes protonated, this leads to a much easier nucleophilic attack. The products for both hydrolyses are compounds with carboxylic acid groups; the oldest commercially practiced example of ester hydrolysis is saponification. It is the hydrolysis of a triglyceride with an aqueous base such as sodium hydroxide. During the process, glycerol is formed, the fatty acids react with the base, converting them to salts; these salts are called soaps used in households. In addition, in living systems, most biochemical reactions take place during the catalysis of enzymes; the catalytic action of enzymes allows the hydrolysis of proteins, fats and carbohydrates. As an example, one may consider proteases, they catalyse the hydrolysis of interior peptide bonds in peptide chains, as opposed to exopeptidases. However, proteases do not catalyse the hydrolysis of all kinds of proteins, their action is stereo-selective: Only proteins with a certain tertiary structure are targeted as some kind of orienting force is needed to place the amide group in the proper position for catalysis.
The necessary contacts between an enzyme and its substrates are created because the enzyme folds in such a way as to form a crevice into which the substrate fits. Therefore, proteins that do not fit into the crevice will not undergo hydrolysis; this specificity preserves the integrity of other proteins such as hormones, therefore the biological system continues to function normally. Upon hydrolysis, an amide converts into an amine or ammonia. One of the two oxygen groups on the carboxylic acid are derived from a water molecule and the amine gains the hydrogen ion; the hydrolysis of peptides gives amino acids. Many polyamide polymers such as nylon 6,6 hydrolyse in the presence of strong acids; the process leads to depolymerization. For this reason nylon products fail by fracturing. Polyesters are susceptible to similar polymer degradation reactions; the problem is known as environmental stress cracking. Hydrolysis is related to energy storage. All living cells require a continual supply of energy for two main purposes: the biosynthesis of micro and macromolecules, the active transport of ions and molecules across cell membranes.
The energy derived from the oxidation of nutrients is not used directly but, by means of a complex and long sequence of reactions, it is channelled into a special energy-storage molecule, adenosine triphosphate. The ATP molecule contains pyrophosphate linkages. ATP can undergo hydrolysis in two ways: the removal of terminal phosphate to form adenosine diphosphate and inorganic phosphate, or the removal of a terminal diphosphate to yield adenosine monophosphate and pyrophosphate; the latter undergoes further cleavage in