1.
Jmol
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Jmol is computer software for molecular modelling chemical structures in 3-dimensions. Jmol returns a 3D representation of a molecule that may be used as a teaching tool and it is written in the programming language Java, so it can run on the operating systems Windows, macOS, Linux, and Unix, if Java is installed. It is free and open-source software released under a GNU Lesser General Public License version 2.0, a standalone application and a software development kit exist that can be integrated into other Java applications, such as Bioclipse and Taverna. A popular feature is an applet that can be integrated into web pages to display molecules in a variety of ways, for example, molecules can be displayed as ball-and-stick models, space-filling models, ribbon diagrams, etc. Jmol supports a range of chemical file formats, including Protein Data Bank, Crystallographic Information File, MDL Molfile. There is also a JavaScript-only version, JSmol, that can be used on computers with no Java, the Jmol applet, among other abilities, offers an alternative to the Chime plug-in, which is no longer under active development. While Jmol has many features that Chime lacks, it does not claim to reproduce all Chime functions, most notably, Chime requires plug-in installation and Internet Explorer 6.0 or Firefox 2.0 on Microsoft Windows, or Netscape Communicator 4.8 on Mac OS9. Jmol requires Java installation and operates on a variety of platforms. For example, Jmol is fully functional in Mozilla Firefox, Internet Explorer, Opera, Google Chrome, fast and Scriptable Molecular Graphics in Web Browsers without Java3D
2.
ChemSpider
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ChemSpider is a database of chemicals. ChemSpider is owned by the Royal Society of Chemistry, the database contains information on more than 50 million molecules from over 500 data sources including, Each chemical is given a unique identifier, which forms part of a corresponding URL. This is an approach to develop an online chemistry database. The search can be used to widen or restrict already found results, structure searching on mobile devices can be done using free apps for iOS and for the Android. The ChemSpider database has been used in combination with text mining as the basis of document markup. The result is a system between chemistry documents and information look-up via ChemSpider into over 150 data sources. ChemSpider was acquired by the Royal Society of Chemistry in May,2009, prior to the acquisition by RSC, ChemSpider was controlled by a private corporation, ChemZoo Inc. The system was first launched in March 2007 in a release form. ChemSpider has expanded the generic support of a database to include support of the Wikipedia chemical structure collection via their WiChempedia implementation. A number of services are available online. SyntheticPages is an interactive database of synthetic chemistry procedures operated by the Royal Society of Chemistry. Users submit synthetic procedures which they have conducted themselves for publication on the site and these procedures may be original works, but they are more often based on literature reactions. Citations to the published procedure are made where appropriate. They are checked by an editor before posting. The pages do not undergo formal peer-review like a journal article. The comments are moderated by scientific editors. The intention is to collect practical experience of how to conduct useful chemical synthesis in the lab, while experimental methods published in an ordinary academic journal are listed formally and concisely, the procedures in ChemSpider SyntheticPages are given with more practical detail. Comments by submitters are included as well, other publications with comparable amounts of detail include Organic Syntheses and Inorganic Syntheses
3.
PubChem
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PubChem is a database of chemical molecules and their activities against biological assays. The system is maintained by the National Center for Biotechnology Information, a component of the National Library of Medicine, PubChem can be accessed for free through a web user interface. Millions of compound structures and descriptive datasets can be downloaded via FTP. PubChem contains substance descriptions and small molecules with fewer than 1000 atoms and 1000 bonds, more than 80 database vendors contribute to the growing PubChem database. PubChem consists of three dynamically growing primary databases, as of 28 January 2016, Compounds,82.6 million entries, contains pure and characterized chemical compounds. Substances,198 million entries, contains also mixtures, extracts, complexes, bioAssay, bioactivity results from 1.1 million high-throughput screening programs with several million values. PubChem contains its own online molecule editor with SMILES/SMARTS and InChI support that allows the import and export of all common chemical file formats to search for structures and fragments. In the text search form the database fields can be searched by adding the name in square brackets to the search term. A numeric range is represented by two separated by a colon. The search terms and field names are case-insensitive, parentheses and the logical operators AND, OR, and NOT can be used. AND is assumed if no operator is used, example,0,5000,50,10 -5,5 PubChem was released in 2004. The American Chemical Society has raised concerns about the publicly supported PubChem database and they have a strong interest in the issue since the Chemical Abstracts Service generates a large percentage of the societys revenue. To advocate their position against the PubChem database, ACS has actively lobbied the US Congress, soon after PubChems creation, the American Chemical Society lobbied U. S. Congress to restrict the operation of PubChem, which they asserted competes with their Chemical Abstracts Service
4.
International Chemical Identifier
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Initially developed by IUPAC and NIST from 2000 to 2005, the format and algorithms are non-proprietary. The continuing development of the standard has supported since 2010 by the not-for-profit InChI Trust. The current version is 1.04 and was released in September 2011, prior to 1.04, the software was freely available under the open source LGPL license, but it now uses a custom license called IUPAC-InChI Trust License. Not all layers have to be provided, for instance, the layer can be omitted if that type of information is not relevant to the particular application. InChIs can thus be seen as akin to a general and extremely formalized version of IUPAC names and they can express more information than the simpler SMILES notation and differ in that every structure has a unique InChI string, which is important in database applications. Information about the 3-dimensional coordinates of atoms is not represented in InChI, the InChI algorithm converts input structural information into a unique InChI identifier in a three-step process, normalization, canonicalization, and serialization. The InChIKey, sometimes referred to as a hashed InChI, is a fixed length condensed digital representation of the InChI that is not human-understandable. The InChIKey specification was released in September 2007 in order to facilitate web searches for chemical compounds and it should be noted that, unlike the InChI, the InChIKey is not unique, though collisions can be calculated to be very rare, they happen. In January 2009 the final 1.02 version of the InChI software was released and this provided a means to generate so called standard InChI, which does not allow for user selectable options in dealing with the stereochemistry and tautomeric layers of the InChI string. The standard InChIKey is then the hashed version of the standard InChI string, the standard InChI will simplify comparison of InChI strings and keys generated by different groups, and subsequently accessed via diverse sources such as databases and web resources. Every InChI starts with the string InChI= followed by the version number and this is followed by the letter S for standard InChIs. The remaining information is structured as a sequence of layers and sub-layers, the layers and sub-layers are separated by the delimiter / and start with a characteristic prefix letter. The six layers with important sublayers are, Main layer Chemical formula and this is the only sublayer that must occur in every InChI. The atoms in the formula are numbered in sequence, this sublayer describes which atoms are connected by bonds to which other ones. Describes how many hydrogen atoms are connected to each of the other atoms, the condensed,27 character standard InChIKey is a hashed version of the full standard InChI, designed to allow for easy web searches of chemical compounds. Most chemical structures on the Web up to 2007 have been represented as GIF files, the full InChI turned out to be too lengthy for easy searching, and therefore the InChIKey was developed. With all databases currently having below 50 million structures, such duplication appears unlikely at present, a recent study more extensively studies the collision rate finding that the experimental collision rate is in agreement with the theoretical expectations. Example, Morphine has the structure shown on the right, as the InChI cannot be reconstructed from the InChIKey, an InChIKey always needs to be linked to the original InChI to get back to the original structure
5.
Simplified molecular-input line-entry system
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The simplified molecular-input line-entry system is a specification in form of a line notation for describing the structure of chemical species using short ASCII strings. SMILES strings can be imported by most molecule editors for conversion back into two-dimensional drawings or three-dimensional models of the molecules, the original SMILES specification was initiated in the 1980s. It has since modified and extended. In 2007, a standard called OpenSMILES was developed in the open-source chemistry community. Other linear notations include the Wiswesser Line Notation, ROSDAL and SLN, the original SMILES specification was initiated by David Weininger at the USEPA Mid-Continent Ecology Division Laboratory in Duluth in the 1980s. The Environmental Protection Agency funded the project to develop SMILES. It has since modified and extended by others, most notably by Daylight Chemical Information Systems. In 2007, a standard called OpenSMILES was developed by the Blue Obelisk open-source chemistry community. Other linear notations include the Wiswesser Line Notation, ROSDAL and SLN, in July 2006, the IUPAC introduced the InChI as a standard for formula representation. SMILES is generally considered to have the advantage of being slightly more human-readable than InChI, the term SMILES refers to a line notation for encoding molecular structures and specific instances should strictly be called SMILES strings. However, the term SMILES is also used to refer to both a single SMILES string and a number of SMILES strings, the exact meaning is usually apparent from the context. The terms canonical and isomeric can lead to confusion when applied to SMILES. The terms describe different attributes of SMILES strings and are not mutually exclusive, typically, a number of equally valid SMILES strings can be written for a molecule. For example, CCO, OCC and CC all specify the structure of ethanol, algorithms have been developed to generate the same SMILES string for a given molecule, of the many possible strings, these algorithms choose only one of them. This SMILES is unique for each structure, although dependent on the algorithm used to generate it. These algorithms first convert the SMILES to a representation of the molecular structure. A common application of canonical SMILES is indexing and ensuring uniqueness of molecules in a database, there is currently no systematic comparison across commercial software to test if such flaws exist in those packages. SMILES notation allows the specification of configuration at tetrahedral centers, and these are structural features that cannot be specified by connectivity alone and SMILES which encode this information are termed isomeric SMILES
6.
Chemical formula
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These are limited to a single typographic line of symbols, which may include subscripts and superscripts. A chemical formula is not a name, and it contains no words. Although a chemical formula may imply certain simple chemical structures, it is not the same as a full chemical structural formula. Chemical formulas can fully specify the structure of only the simplest of molecules and chemical substances, the simplest types of chemical formulas are called empirical formulas, which use letters and numbers indicating the numerical proportions of atoms of each type. Molecular formulas indicate the numbers of each type of atom in a molecule. For example, the formula for glucose is CH2O, while its molecular formula is C6H12O6. This is possible if the relevant bonding is easy to show in one dimension, an example is the condensed molecular/chemical formula for ethanol, which is CH3-CH2-OH or CH3CH2OH. For reasons of structural complexity, there is no condensed chemical formula that specifies glucose, chemical formulas may be used in chemical equations to describe chemical reactions and other chemical transformations, such as the dissolving of ionic compounds into solution. A chemical formula identifies each constituent element by its chemical symbol, in empirical formulas, these proportions begin with a key element and then assign numbers of atoms of the other elements in the compound, as ratios to the key element. For molecular compounds, these numbers can all be expressed as whole numbers. For example, the formula of ethanol may be written C2H6O because the molecules of ethanol all contain two carbon atoms, six hydrogen atoms, and one oxygen atom. Some types of compounds, however, cannot be written with entirely whole-number empirical formulas. An example is boron carbide, whose formula of CBn is a variable non-whole number ratio with n ranging from over 4 to more than 6.5. When the chemical compound of the consists of simple molecules. These types of formulas are known as molecular formulas and condensed formulas. A molecular formula enumerates the number of atoms to reflect those in the molecule, so that the formula for glucose is C6H12O6 rather than the glucose empirical formula. However, except for very simple substances, molecular chemical formulas lack needed structural information, for simple molecules, a condensed formula is a type of chemical formula that may fully imply a correct structural formula. For example, ethanol may be represented by the chemical formula CH3CH2OH
7.
Glycolysis
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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, glycolysis is a determined sequence of ten enzyme-catalyzed reactions. The intermediates provide entry points to glycolysis, for example, most monosaccharides, such as fructose and galactose, can be converted to one of these intermediates. The intermediates may also 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, meaning that it not use molecular oxygen for any of its reactions. However the products of glycolysis are sometimes metabolized using atmospheric oxygen, when molecular oxygen is used for the metabolism of the products of glycolysis the process is usually referred to as aerobic, whereas if no oxygen is used the process is said to be anaerobic. Thus, glycolysis occurs, with variations, in all organisms. The wide occurrence of glycolysis indicates that it is one of the most ancient metabolic pathways, glycolysis could thus have originated from chemical constraints of the prebiotic world. Glycolysis occurs in most organisms in the cytosol of the cell, the most common type of glycolysis is the Embden–Meyerhof–Parnas, which was discovered by Gustav Embden, Otto Meyerhof, and Jakub Karol Parnas. Glycolysis also refers to other pathways, such as the Entner–Doudoroff pathway, however, the discussion here will be limited to the Embden–Meyerhof–Parnas pathway. The overall reaction of glycolysis is, The use of symbols in this equation makes it appear unbalanced with respect to oxygen atoms, hydrogen atoms, and charges. In the cellular environment, all three groups of ADP dissociate into −O− and H+, giving ADP3−, and this ion tends to exist in an ionic bond with Mg2+. ATP behaves identically except that it has four groups, giving ATPMg2−. When these differences along with the 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 then 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, the pathway of glycolysis as it is known today took almost 100 years to fully discover. The combined results of many experiments were required in order to understand the pathway as a whole
8.
Cellular respiration
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Respiration is one of the key ways a cell releases chemical energy to fuel cellular activity. Cellular respiration is considered an exothermic reaction which releases heat. The overall reaction occurs in a series of steps, most of which are redox reactions themselves. Nutrients that are used by animal and plant cells in respiration include sugar, amino acids and fatty acids. The chemical energy stored in ATP can then be used to drive processes requiring energy, including biosynthesis, aerobic respiration requires oxygen in order to create ATP. The potential of NADH and FADH2 is converted to more ATP through a transport chain with oxygen as the terminal electron acceptor. Most of the ATP produced by cellular respiration is made by oxidative phosphorylation. This works by the released in the consumption of pyruvate being used to create a chemiosmotic potential by pumping protons across a membrane. This potential is used to drive ATP synthase and produce ATP from ADP. Biology textbooks often state that 38 ATP molecules can be made per oxidised glucose molecule during cellular respiration, aerobic metabolism is up to 15 times more efficient than anaerobic metabolism. They share the pathway of glycolysis but aerobic metabolism continues with the Krebs cycle. The post-glycolytic reactions take place in the mitochondria in eukaryotic cells, glycolysis is a metabolic pathway that takes place in the cytosol of cells in all living organisms. This pathway can function with or without the presence of oxygen, in humans, aerobic conditions produce pyruvate and anaerobic conditions produce lactate. In aerobic conditions, the process converts one molecule of glucose into two molecules of pyruvate, generating energy in the form of two net molecules of ATP, four molecules of ATP per glucose are actually produced, however, two are consumed as part of the preparatory phase. The initial phosphorylation of glucose is required to increase the reactivity in order for the molecule to be cleaved into two molecules by the enzyme aldolase. During the pay-off phase of glycolysis, four groups are transferred to ADP by substrate-level phosphorylation to make four ATP. Glycogen can be converted into glucose 6-phosphate as well with the help of glycogen phosphorylase, during energy metabolism, glucose 6-phosphate becomes fructose 6-phosphate. An additional ATP is used to phosphorylate fructose 6-phosphate into fructose 1, fructose 1, 6-diphosphate then splits into two phosphorylated molecules with three carbon chains which later degrades into pyruvate
9.
Light-independent reactions
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The Carbon reactions of photosynthesis are chemical reactions that convert carbon dioxide and other compounds into glucose. These reactions occur in the stroma, the area of a chloroplast outside of the thylakoid membranes. These reactions take the products of light-dependent reactions and perform further chemical processes on them, there are three phases to the light-independent reactions, collectively called the Calvin cycle, carbon fixation, reduction reactions, and ribulose 1, 5-bisphosphate regeneration. This process occurs only when light is available, plants do not carry out the Calvin cycle during nighttime. They instead release sucrose into the phloem from their starch reserves. They are also known as dark reactions and these reactions are closely coupled to the thylakoid electron transport chain as reducing power provided by NADPH produced in the photosystem I is actively needed. The cycle was discovered by Melvin Calvin, James Bassham, and Andrew Benson at the University of California, photosynthesis occurs in two stages in a cell. In the first stage, light-dependent reactions capture the energy of light and use it to make the energy-storage and transport molecules ATP, the Calvin cycle uses the energy from short-lived electronically excited carriers to convert carbon dioxide and water into organic compounds that can be used by the organism. This set of reactions is called carbon fixation. The key enzyme of the cycle is called RuBisCO, in the following biochemical equations, the chemical species exist in equilibria among their various ionized states as governed by the pH. They are activated in the light, and also by products of the light-dependent reaction and these regulatory functions prevent the Calvin cycle from being respired to carbon dioxide. Energy would be wasted in carrying out these reactions that have no net productivity, although many texts list a product of photosynthesis as C 6H 12O6, this is mainly a convenience to counter the equation of respiration, where six-carbon sugars are oxidized in mitochondria. The carbohydrate products of the Calvin cycle are three-carbon sugar phosphate molecules, or triose phosphates, namely, the three steps involved are, The enzyme RuBisCO catalyses the carboxylation of ribulose-1, 5-bisphosphate, RuBP, a 5-carbon compound, by carbon dioxide in a two-step reaction. The product of the first step is enediol-enzyme complex that can capture CO2 or O2, thus, enediol-enzyme complex is the real carboxylase/oxygenase. The enzyme phosphoglycerate kinase catalyses the phosphorylation of 3-PGA by ATP,1, 3-Bisphosphoglycerate and ADP are the products. The enzyme glyceraldehyde 3-phosphate dehydrogenase catalyses the reduction of 1, 3BPGA by NADPH, glyceraldehyde 3-phosphate is produced, and the NADPH itself is oxidized and becomes NADP+. Again, two NADPH are utilized per CO2 fixed, the next stage in the Calvin cycle is to regenerate RuBP. Five G3P molecules produce three RuBP molecules, using up three molecules of ATP, the regeneration stage can be broken down into steps. Triose phosphate isomerase converts all of the G3P reversibly into dihydroxyacetone phosphate, aldolase and fructose-1, 6-bisphosphatase convert a G3P and a DHAP into fructose 6-phosphate
10.
Photosynthesis
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Photosynthesis is a process used by plants and other organisms to convert light energy into chemical energy that can later be released to fuel the organisms activities. In most cases, oxygen is released as a waste product. Most plants, most algae, and cyanobacteria perform photosynthesis, such organisms are called photoautotrophs, in plants, these proteins are held inside organelles called chloroplasts, which are most abundant in leaf cells, while in bacteria they are embedded in the plasma membrane. In these light-dependent reactions, some energy is used to strip electrons from suitable substances, such as water, in the Calvin cycle, atmospheric carbon dioxide is incorporated into already existing organic carbon compounds, such as ribulose bisphosphate. Using the ATP and NADPH produced by the light-dependent reactions, the compounds are then reduced and removed to form further carbohydrates. Cyanobacteria appeared later, the oxygen they produced contributed directly to the oxygenation of the Earth. Today, the rate of energy capture by photosynthesis globally is approximately 130 terawatts. Photosynthetic organisms also convert around 100–115 thousand million tonnes of carbon into biomass per year. Photosynthetic organisms are photoautotrophs, which means that they are able to synthesize food directly from carbon dioxide, however, not all organisms that use light as a source of energy carry out photosynthesis, photoheterotrophs use organic compounds, rather than carbon dioxide, as a source of carbon. In plants, algae, and cyanobacteria, photosynthesis releases oxygen and this is called oxygenic photosynthesis and is by far the most common type of photosynthesis used by living organisms. Although there are differences between oxygenic photosynthesis in plants, algae, and cyanobacteria, the overall process is quite similar in these organisms. There are also varieties of anoxygenic photosynthesis, used mostly by certain types of bacteria. Carbon dioxide is converted into sugars in a process called carbon fixation, photosynthesis provides the energy in the form of free electrons that are used to split carbon from carbon dioxide that is then used to fix that carbon once again as carbohydrate. Carbon fixation is a redox reaction, so photosynthesis supplies the energy that drives both process. In the first stage, light-dependent reactions or light reactions capture the energy of light and use it to make the energy-storage molecules ATP, during the second stage, the light-independent reactions use these products to capture and reduce carbon dioxide. Most organisms that utilize oxygenic photosynthesis use visible light for the light-dependent reactions, some organisms employ even more radical variants of photosynthesis. Some archea use a method that employs a pigment similar to those used for vision in animals. The bacteriorhodopsin changes its configuration in response to sunlight, acting as a proton pump and this produces a proton gradient more directly, which is then converted to chemical energy
11.
3-Phosphoglyceric acid
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3-Phosphoglyceric acid, or glycerate 3-phosphate, is a biochemically significant 3-carbon molecule that is a metabolic intermediate in both glycolysis and the Calvin cycle. This chemical is often termed PGA when referring to the Calvin cycle, in the Calvin cycle, 3-Phosphoglycerate is the product of the spontaneous split of an unstable 6-carbon intermediate formed by CO2 fixation. Thus, two 3-phosphoglycerate molecules are produced for each molecule of CO2 fixed, compound C00236 at KEGG Pathway Database. Enzyme 2.7.2.3 at KEGG Pathway Database, compound C00197 at KEGG Pathway Database. Enzyme 5.4.2.1 at KEGG Pathway Database, compound C00631 at KEGG Pathway Database. Click on genes, proteins and metabolites below to link to respective articles and this is the first compound formed during the C3 or Calvin cycle. It is a biomolecule that is easily reduced. Glycerate 3-phosphate is also a precursor for serine, which, in turn, can create cysteine and glycine through the homocysteine cycle
12.
2,3-Bisphosphoglyceric acid
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2, 3-Bisphosphoglyceric acid, also known as 2, 3-diphosphoglyceric acid, is a three-carbon isomer of the glycolytic intermediate 1, 3-bisphosphoglyceric acid. 2, 3-BPG is present in red blood cells at approximately 5 mmol/L. 2, 3-BPG is thus an allosteric effector and its function was discovered in 1967 by Reinhold Benesch and Ruth Benesch. 2, 3-BPG is formed from 1, 3-BPG by the enzyme BPG mutase and it can then be broken down by 2, 3-BPG phosphatase to form 3-phosphoglycerate. 2, 3-BPG, the most concentrated organophosphate in the erythrocyte, the concentration of 2, 3-BPG varies proportionately to the, which is inhibitory to catalytic action of bisphosphoglycerate phosphatase. There is a balance between the need to generate ATP to support energy requirements for cell metabolism and the need to maintain appropriate oxygenation/deoxygenation status of hemoglobin. This balance is maintained by isomerisation of 1, 3-BPG to 2, 3-BPG, low pH activates the activity of biphosphoglyceromutase and inhibits bisphosphoglyerate phosphatase, which leads to increases in 2, 3-BPG. When 2, 3-BPG binds to deoxyhemoglobin, it acts to stabilize the low affinity state of the oxygen carrier. The R state, with oxygen bound to a group, has a different conformation. By itself, hemoglobin has sigmoid-like kinetics, in selectively binding to deoxyhemoglobin,2, 3-BPG stabilizes the T state conformation, making it harder for oxygen to bind hemoglobin and more likely to be released to adjacent tissues. 2, 3-BPG is part of a loop that can help prevent tissue hypoxia in conditions where it is most likely to occur. Ultimately, this mechanism increases oxygen release from RBCs under circumstances where it is needed most and this release is potentiated by the Bohr effect in tissues with high energetic demands. Bohr effect is another way to solve the affinity problem of the hemoglobin, and it is related to the pH. It’s important to highlight that the behaviour of myoglobin doesn’t work in the way, as 2. In pregnant women, there is a 30% increase in intracellular 2 and this lowers the maternal hemoglobin affinity for oxygen, and therefore allows more oxygen to be offloaded to the fetus in the maternal uterine arteries. The foetus has a low sensitivity to 2, 3-BPG, so its hemoglobin has an affinity for oxygen. Therefore although the pO2 in the arteries is low, the foetal umbilical arteries can still get oxygenated from them. It is interesting to note that fetal hemoglobin exhibits a low affinity for 2, 3-BPG and this increased oxygen-binding affinity relative to that of adult hemoglobin is due to HbFs having two α/γ dimers as opposed to the two α/β dimers of HbA
13.
Conjugate acid
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A conjugate acid, within the Brønsted–Lowry acid–base theory, is a species formed by the reception of a proton by a base—in other words, it is a base with a hydrogen ion added to it. On the other hand, a base is merely what is left after an acid has donated a proton in a chemical reaction. Hence, a base is a species formed by the removal of a proton from an acid. A proton is a particle with a unit positive electrical charge, it is represented by the symbol H+ because it constitutes the nucleus of a hydrogen atom, that is. A cation can be an acid, and an anion can be a conjugate base, depending on which substance is involved. In an acid-base reaction, an acid plus a base reacts to form a conjugate base plus a conjugate acid, refer to the following figure, We say that the water molecule is the conjugate acid of the hydroxide ion after the latter received the hydrogen proton donated by ammonium. On the other hand, ammonia is the base for the acid ammonium after ammonium has donated a hydrogen ion towards the production of the water molecule. The strength of an acid is directly proportional to its dissociation constant. If a conjugate acid is strong, its dissociation will have an equilibrium constant. The strength of a base can be seen as the tendency of the species to pull hydrogen protons towards itself. If a conjugate base is classified as strong, it will hold on to the hydrogen proton when in solution, if a chemical species is classified as a weak acid, its conjugate base will be strong in nature. This can be observed in ammonias reaction with water, the reaction proceeds until most of the ammonia has been transformed to ammonium. This shift to the right in the equilibrium of the reaction means that ammonium does not dissociate easily in water. On the other hand, if a species is classified as a strong acid, an example of this case would be the dissociation of Hydrochloric acid HCl in water. Since HCl is an acid, its conjugate base will be a weak conjugate base. Therefore, in system, most H+ will be in the form of a Hydronium ion H 3O+ instead of attached to a Cl anion. To summarize, the stronger the acid or base, the weaker the conjugate, the acid and conjugate base as well as the base and conjugate acid are known as conjugate pairs. When finding a conjugate acid or base, it is important to look at the reactants of the chemical equation, to identify the conjugate acid, look for the pair of compounds that are related
14.
Adenosine diphosphate
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Adenosine pyrophosphate is an important organic compound in metabolism and is essential to the flow of energy in living cells. A molecule of APP/ADP consists of three important structural components, a sugar backbone attached to a molecule of adenine and two phosphate groups bonded to the 5 carbon atom of ribose. The two phosphate groups of APP are added in series to the 5’ carbon of the sugar backbone, the two phosphates in APP can be correlated with ATP and AMP. Energy transfer used by all living things is a result of dephosphorylation of ATP by enzymes known as ATPases, the cleavage of a phosphate group from ATP results in the coupling of energy to metabolic reactions and a by-product, a molecule of APP. Being the molecular unit of currency, ATP is continually being formed from molecules of APP. APP-ATP cycling supplies the energy needed to do work in a biological system, there are two types of energy, potential energy and kinetic energy. Potential energy can be thought of as stored energy, or usable energy that is available to do work, kinetic energy is the energy of an object as a result of its motion. The significance of ATP is in its ability to potential energy within the phosphate bonds. The energy stored between these bonds can then be transferred to do work, for example, the transfer of energy from ATP to the protein myosin causes a conformational change when connecting to actin during muscle contraction. For this reason, biological processes have evolved to produce efficient ways to replenishment the potential energy of ATP from APP, breaking one of ATP’s phosphorus bonds generates approximately 30.5 kilojoules per Mole of ATP. Plants use photosynthetic pathways to convert and store energy from sunlight, animals use the energy released in the breakdown of glucose and other molecules to convert APP to ATP, which can then be used to fuel necessary growth and cell maintenance. The ten-step catabolic pathway of glycolysis is the phase of free-energy release in the breakdown of glucose. APP and phosphate are needed as precursors to synthesize ATP in the reactions of the TCA cycle. During the payoff phase of glycolysis, the enzymes phosphoglycerate kinase, glycolysis is performed by all living organisms and consists of 10 steps. The net reaction for the process of glycolysis is, Glucose + 2NAD+ +2 Pi +2 APP =2 pyruvate +2 ATP +2 NADH +2 H2O. Steps 1 and 3 require the input of energy derived from the hydrolysis of ATP to APP and Pi, whereas steps 7 and 10 require the input of an APP molecule, each yielding an ATP molecule. The enzymes necessary to break down glucose are found in the cytoplasm, the fluid that fills living cells. It is only in step 5, where GTP is generated, by succinyl-CoA synthetase, and then converted to ATP, oxidative phosphorylation produces 26 of the 30 molecules of ATP generated in cellular respiration by transferring electrons from NADH or FADH2 to O2 through electron carriers
15.
Glyceraldehyde 3-phosphate dehydrogenase
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Glyceraldehyde 3-phosphate dehydrogenase is an enzyme of ~37kDa that catalyzes the sixth step of glycolysis and thus serves to break down glucose for energy and carbon molecules. In sperm, a testis-specific isoenzyme GAPDHS is expressed, under normal cellular conditions, cytoplasmic GAPDH exists primarily as a tetramer. This form is composed of four identical 37-kDa subunits containing a single catalytic thiol group each, nuclear GAPDH has increased isoelectric point of pH8. 3–8.7. Of note, the cysteine residue C152 in the active site is required for the induction of apoptosis by oxidative stress. Notably, post-translational modifications of cytoplasmic GAPDH contribute to its functions outside of glycolysis, compound C00118 at KEGG Pathway Database. Enzyme 1.2.1.12 at KEGG Pathway Database, reaction R01063 at KEGG Pathway Database. Compound C00236 at KEGG Pathway Database and this is an example of phosphorylation coupled to oxidation, and the overall reaction is somewhat endergonic. Energy coupling here is possible by GAPDH. GAPDH uses covalent catalysis and general base catalysis to decrease the very large, first, a cysteine residue in the active site of GAPDH attacks the carbonyl group of GAP, creating a hemithioacetal intermediate. Next, an adjacent, tightly bound molecule of NAD+ accepts a hydride ion from GAP, forming NADH and this thioester species is much higher in energy than the carboxylic acid species that would result in the absence of GAPDH. Donation of the ion by the hemithioacetal is facilitated by its deprotonation by a histidine residue in the enzymes active site. Deprotonation encourages the reformation of the group in the thioester intermediate. This protein may use the model of allosteric regulation. As its name indicates, glyceraldehyde 3-phosphate dehydrogenase catalyses the conversion of glyceraldehyde 3-phosphate to D-glycerate 1 and this is the 6th step in the glycolytic breakdown of glucose, an important pathway of energy and carbon molecule supply which takes place in the cytosol of eukaryotic cells. The conversion occurs in two coupled steps, the first is favourable and allows the second unfavourable step to occur. The OCA-S transcriptional coactivator complex contains GAPDH and lactate dehydrogenase, two proteins previously thought to be involved in metabolism. GAPDH moves between the cytosol and the nucleus and may link the metabolic state to gene transcription. In 2005, Hara et al. showed that GAPDH initiates apoptosis and this is not a third function, but can be seen as an activity mediated by GAPDH binding to DNA like in transcription activation, discussed above
16.
1,3-Bisphosphoglyceric acid
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1, 3-Bisphosphoglyceric acid is a 3-carbon organic molecule present in most, if not all, living organisms. It primarily exists as an intermediate in both glycolysis during respiration and the Calvin cycle during photosynthesis. 1, 3BPG is a stage between glycerate 3-phosphate and glyceraldehyde 3-phosphate during the fixation/reduction of CO2. 1, 3BPG is also a precursor to 2, 3-bisphosphoglycerate which in turn is an intermediate in the glycolytic pathway. 1, 3-Bisphosphoglycerate is the base of 1, 3-bisphosphoglyceric acid. It is phosphorylated at the number 1 and 3 carbons, the result of this phosphorylation gives 1, 3BPG important biological properties such as the ability to phosphorylate ADP to form the energy storage molecule ATP. Compound C00118 at KEGG Pathway Database, enzyme 1.2.1.12 at KEGG Pathway Database. Compound C00236 at KEGG Pathway Database, enzyme 2.7.2.3 at KEGG Pathway Database. Compound C00197 at KEGG Pathway Database, as previously mentioned 1, 3BPG is a metabolic intermediate in the glycolytic pathway. It is created by the oxidation of the aldehyde in G3P. The result of oxidation is the conversion of the aldehyde group into a carboxylic acid group which drives the formation of an acyl phosphate bond. This is incidentally the only step in the pathway in which NAD+ is converted into NADH. The formation reaction of 1, 3BPG requires the presence of an enzyme called glyceraldehyde-3-phosphate dehydrogenase, the high-energy acyl phosphate bond of 1, 3BPG is important in respiration as it assists in the formation of ATP. The molecule of ATP created during the reaction is the first molecule produced during respiration. This is as a result of one acyl phosphate bond being cleaved whilst another is created and this reaction is not naturally spontaneous and requires the presence of a catalyst. This role is performed by the enzyme phosphoglycerate kinase, during the reaction phosphoglycerate kinase undergoes a substrate induced conformational change similar to another metabolic enzyme called hexokinase. Glycolysis also uses two molecules of ATP in its initial stages as a committed and irreversible step, for this reason glycolysis is not reversible and has a net produce of 2 molecules of ATP and two of NADH. The two molecules of NADH themselves go on to produce approximately 3 molecules of ATP each, click on genes, proteins and metabolites below to link to respective articles
17.
Phosphoglycerate kinase
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Phosphoglycerate kinase is an enzyme that catalyzes the reversible transfer of a phosphate group from 1, 3-bisphosphoglycerate to ADP producing 3-phosphoglycerate and ATP. Like all kinases it is a transferase, PGK is a major enzyme used in glycolysis, in the first ATP-generating step of the glycolytic pathway. In gluconeogenesis, the reaction catalyzed by PGK proceeds in the direction, generating ADP and 1. In humans, two isozymes of PGK have been so far identified, PGK1 and PGK2, PGK is present in all living organisms as one of the two ATP-generating enzymes in glycolysis. In the gluconeogenic pathway, PGK catalyzes the reverse reaction, under biochemical standard conditions, the glycolytic direction is favored. In the Calvin cycle in photosynthetic organisms, PGK catalyzes the phosphorylation of 3-PG, producing 1, 3-BPG and ADP, as part of the reactions that regenerate ribulose-1, 5-bisphosphate. PGK has been reported to exhibit thiol reductase activity on plasmin, leading to angiostatin formation, the enzyme was also shown to participate in DNA replication and repair in mammal cell nuclei. The human isozyme PGK2, which is expressed during spermatogenesis, was shown to be essential for sperm function in mice. Click on genes, proteins and metabolites below to link to respective articles, PGK is found in all living organisms and its sequence has been highly conserved throughout evolution. The enzyme exists as a 415-residue monomer containing two nearly equal-sized domains that correspond to the N- and C-termini of the protein, 3-phosphoglycerate binds to the N-terminal, while the nucleotide substrates, MgATP or MgADP, bind to the C-terminal domain of the enzyme. This extended two-domain structure is associated with large-scale hinge-bending conformational changes, the two domains of the protein are separated by a cleft and linked by two alpha-helices. At the core of each domain is a 6-stranded parallel beta-sheet surrounded by alpha helices, the two lobes are capable of folding independently, consistent with the presence of intermediates on the folding pathway with a single domain folded. Though the binding of either substrate triggers a change, only through the binding of both substrates does domain closure occur, leading to the transfer of the phosphate group. Magnesium ions are complexed to the phosphate groups the nucleotide substrates of PGK. It is known that in the absence of magnesium, no enzyme activity occurs and it is theorized that the ion may also encourage domain closure when PGK has bound both substrates. Without either substrate bound, PGK exists in an open conformation, then, in the case of the forward glycolytic reaction, the beta-phosphate of ADP initiates a nucleophilic attack on the 1-phosphate of 1, 3-BPG. The Lys219 on the enzyme guides the group to the substrate. In the glycolytic pathyway,1, 3-BPG is the donor and has a high phosphoryl-transfer potential
18.
Adenosine triphosphate
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Adenosine triphosphate is a nucleotide, also called a nucleoside triphosphate, is a small molecule used in cells as a coenzyme. It is often referred to as the unit of currency of intracellular energy transfer. ATP transports chemical energy within cells for metabolism, most cellular functions need energy in order to be carried out, synthesis of proteins, synthesis of membranes, movement of the cell, cellular division, transport of various solutes etc. The ATP is the molecule that carries energy to the place where the energy is needed, when ATP breaks into ADP and Pi, the breakdown of the last covalent link of phosphate liberates energy that is used in reactions where it is needed. Substrate-level phosphorylation, oxidative phosphorylation in cellular respiration, and photophosphorylation in photosynthesis are three mechanisms of ATP biosynthesis. Metabolic processes that use ATP as an energy source convert it back into its precursors, ATP is therefore continuously recycled in organisms, the human body, which on average contains only 250 grams of ATP, turns over its own body weight equivalent in ATP each day. ATP is used as a substrate in signal transduction pathways by kinases that phosphorylate proteins and it is also used by adenylate cyclase, which uses ATP to produce the second messenger molecule cyclic AMP. The ratio between ATP and AMP is used as a way for a cell to sense how much energy is available and control the metabolic pathways that produce and consume ATP. Apart from its roles in signaling and energy metabolism, ATP is also incorporated into nucleic acids by polymerases in the process of transcription, ATP is the neurotransmitter believed to signal the sense of taste. The structure of this consists of a purine base attached by the 9′ nitrogen atom to the 1′ carbon atom of a pentose sugar. Three phosphate groups are attached at the 5′ carbon atom of the pentose sugar and it is the addition and removal of these phosphate groups that inter-convert ATP, ADP and AMP. When ATP is used in DNA synthesis, the sugar is first converted to deoxyribose by ribonucleotide reductase. ATP was discovered in 1929 by Karl Lohmann, and independently by Cyrus Fiske and Yellapragada Subbarow of Harvard Medical School and it was proposed to be the intermediary molecule between energy-yielding and energy-requiring reactions in cells by Fritz Albert Lipmann in 1941. It was first artificially synthesized by Alexander Todd in 1948, ATP consists of adenosine – composed of an adenine ring and a ribose sugar – and three phosphate groups. The phosphoryl groups, starting with the group closest to the ribose, are referred to as the alpha, beta, consequently, it is closely related to the adenosine nucleotide, a monomer of RNA. ATP is highly soluble in water and is stable in solutions between pH6.8 and 7.4, but is rapidly hydrolysed at extreme pH. Consequently, ATP is best stored as an anhydrous salt, ATP is an unstable molecule in unbuffered water, in which it hydrolyses to ADP and phosphate. This is because the strength of the bonds between the groups in ATP is less than the strength of the hydrogen bonds, between its products, and water
19.
Redox
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Redox is a chemical reaction in which the oxidation states of atoms are changed. Any such reaction involves both a process and a complementary oxidation process, two key concepts involved with electron transfer processes. Redox reactions include all chemical reactions in which atoms have their oxidation state changed, in general, the chemical species from which the electron is stripped is said to have been oxidized, while the chemical species to which the electron is added is said to have been reduced. It can be explained in terms, Oxidation is the loss of electrons or an increase in oxidation state by a molecule, atom. Reduction is the gain of electrons or a decrease in state by a molecule, atom. As an example, during the combustion of wood, oxygen from the air is reduced, the reaction can occur relatively slowly, as in the case of rust, or more quickly, as in the case of fire. Redox is a portmanteau of reduction and oxidation, the word oxidation originally implied reaction with oxygen to form an oxide, since dioxygen was historically the first recognized oxidizing agent. Later, the term was expanded to encompass oxygen-like substances that accomplished parallel chemical reactions, ultimately, the meaning was generalized to include all processes involving loss of electrons. The word reduction originally referred to the loss in weight upon heating a metallic ore such as an oxide to extract the metal. In other words, ore was reduced to metal, antoine Lavoisier showed that this loss of weight was due to the loss of oxygen as a gas. Later, scientists realized that the atom gains electrons in this process. The meaning of reduction then became generalized to all processes involving gain of electrons. Even though reduction seems counter-intuitive when speaking of the gain of electrons, it help to think of reduction as the loss of oxygen. Since electrons are charged, it is also helpful to think of this as reduction in electrical charge. The electrochemist John Bockris has used the words electronation and deelectronation to describe reduction and oxidation processes respectively when they occur at electrodes and these words are analogous to protonation and deprotonation, but they have not been widely adopted by chemists. The term hydrogenation could be used instead of reduction, since hydrogen is the agent in a large number of reactions. But, unlike oxidation, which has been generalized beyond its root element, the word redox was first used in 1928. The processes of oxidation and reduction occur simultaneously and cannot happen independently of one another, the oxidation alone and the reduction alone are each called a half-reaction, because two half-reactions always occur together to form a whole reaction
20.
Aldehyde
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The group—without R—is the aldehyde group, also known as the formyl group. Aldehydes are common in organic chemistry, Aldehydes feature an sp2-hybridized, planar carbon center that is connected by a double bond to oxygen and a single bond to hydrogen. The C–H bond is not ordinarily acidic, because of resonance stabilization of the conjugate base, an α-hydrogen in an aldehyde is far more acidic, with a pKa near 15, compared to the acidity of a typical alkane. This acidification is attributed to the quality of the formyl center and the fact that the conjugate base. Related to, the group is somewhat polar. Aldehydes can exist in either the keto or the enol tautomer, keto-enol tautomerism is catalyzed by either acid or base. Usually the enol is the minority tautomer, but it is more reactive, the common names for aldehydes do not strictly follow official guidelines, such as those recommended by IUPAC, but these rules are useful. IUPAC prescribes the following nomenclature for aldehydes, Acyclic aliphatic aldehydes are named as derivatives of the longest carbon chain containing the aldehyde group, thus, HCHO is named as a derivative of methane, and CH3CH2CH2CHO is named as a derivative of butane. The name is formed by changing the suffix -e of the parent alkane to -al, so that HCHO is named methanal, in other cases, such as when a -CHO group is attached to a ring, the suffix -carbaldehyde may be used. Thus, C6H11CHO is known as cyclohexanecarbaldehyde, if the presence of another functional group demands the use of a suffix, the aldehyde group is named with the prefix formyl-. This prefix is preferred to methanoyl-, the word aldehyde was coined by Justus von Liebig as a contraction of the Latin alcohol dehydrogenatus. In the past, aldehydes were sometimes named after the corresponding alcohols, for example, the term formyl group is derived from the Latin word formica ant. This word can be recognized in the simplest aldehyde, formaldehyde, Aldehydes have properties that are diverse and that depend on the remainder of the molecule. Smaller aldehydes are more soluble in water, formaldehyde and acetaldehyde completely so, the volatile aldehydes have pungent odors. Aldehydes degrade in air via the process of autoxidation, the two aldehydes of greatest importance in industry, formaldehyde and acetaldehyde, have complicated behavior because of their tendency to oligomerize or polymerize. They also tend to hydrate, forming the geminal diol, the oligomers/polymers and the hydrates exist in equilibrium with the parent aldehyde. Aldehydes are readily identified by spectroscopic methods, using IR spectroscopy, they display a strong νCO band near 1700 cm−1. In their 1H NMR spectra, the formyl hydrogen center absorbs near δH =9 and this signal shows the characteristic coupling to any protons on the alpha carbon
21.
Carboxylic acid
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A carboxylic acid /ˌkɑːrbɒkˈsɪlɪk/ is an organic compound that contains a carboxyl group. The general formula of an acid is R–COOH, with R referring to the rest of the molecule. Carboxylic acids occur widely and include the amino acids and acetic acid, salts and esters of carboxylic acids are called carboxylates. When a carboxyl group is deprotonated, its conjugate base forms a carboxylate anion, carboxylate ions are resonance-stabilized, and this increased stability makes carboxylic acids more acidic than alcohols. Carboxylic acids can be seen as reduced or alkylated forms of the Lewis acid carbon dioxide, carboxylic acids are commonly identified using their trivial names, and usually have the suffix -ic acid. IUPAC-recommended names also exist, in system, carboxylic acids have an -oic acid suffix. For example, butyric acid is butanoic acid by IUPAC guidelines, the -oic acid nomenclature detail is based on the name of the previously-known chemical benzoic acid. Alternately, it can be named as a carboxy or carboxylic acid substituent on another parent structure, for example, 2-carboxyfuran. The carboxylate anion of an acid is usually named with the suffix -ate, in keeping with the general pattern of -ic acid and -ate for a conjugate acid and its conjugate base. For example, the base of acetic acid is acetate. The radical •COOH has only a fleeting existence. The acid dissociation constant of •COOH has been measured using electron paramagnetic resonance spectroscopy, the carboxyl group tends to dimerise to form oxalic acid. Because they are both hydrogen-bond acceptors and hydrogen-bond donors, they participate in hydrogen bonding. Together the hydroxyl and carbonyl group forms the functional group carboxyl, carboxylic acids usually exist as dimeric pairs in nonpolar media due to their tendency to self-associate. Smaller carboxylic acids are soluble in water, whereas higher carboxylic acids are less due to the increasing hydrophobic nature of the alkyl chain. These longer chain acids tend to be soluble in less-polar solvents such as ethers. Carboxylic acids tend to have higher boiling points than water, not only because of their surface area. Carboxylic acids tend to evaporate or boil as these dimers, for boiling to occur, either the dimer bonds must be broken or the entire dimer arrangement must be vaporised, both of which increase the enthalpy of vaporization requirements significantly
22.
Nicotinamide adenine dinucleotide
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Nicotinamide adenine dinucleotide is a coenzyme found in all living cells. The compound is a dinucleotide, because it consists of two nucleotides joined through their phosphate groups, one nucleotide contains an adenine base and the other nicotinamide. Nicotinamide adenine dinucleotide exists in two forms, an oxidized and reduced form abbreviated as NAD+ and NADH respectively, in metabolism, nicotinamide adenine dinucleotide is involved in redox reactions, carrying electrons from one reaction to another. The coenzyme is, therefore, found in two forms in cells, NAD+ is an oxidizing agent – it accepts electrons from other molecules and becomes reduced and this reaction forms NADH, which can then be used as a reducing agent to donate electrons. These electron transfer reactions are the function of NAD. However, it is used in other cellular processes, the most notable one being a substrate of enzymes that add or remove chemical groups from proteins. Because of the importance of these functions, the involved in NAD metabolism are targets for drug discovery. In organisms, NAD can be synthesized from simple building-blocks from the amino acids tryptophan or aspartic acid, in an alternative fashion, more complex components of the coenzymes are taken up from food as the vitamin called niacin. Similar compounds are released by reactions that break down the structure of NAD and these preformed components then pass through a salvage pathway that recycles them back into the active form. Some NAD is also converted into nicotinamide adenine dinucleotide phosphate, the chemistry of this related coenzyme is similar to that of NAD, nicotinamide adenine dinucleotide, like all dinucleotides, consists of two nucleosides joined by a pair of bridging phosphate groups. The nucleosides each contain a ring, one with adenine attached to the first carbon atom. The nicotinamide moiety can be attached in two orientations to this carbon atom. Because of these two structures, the compound exists as two diastereomers. It is the diastereomer of NAD+ that is found in organisms. These nucleotides are joined together by a bridge of two groups through the 5 carbons. In metabolism, the compound accepts or donates electrons in redox reactions, such reactions involve the removal of two hydrogen atoms from the reactant, in the form of a hydride ion, and a proton. The proton is released into solution, while the reductant RH2 is oxidized, the midpoint potential of the NAD+/NADH redox pair is −0.32 volts, which makes NADH a strong reducing agent. The reaction is reversible, when NADH reduces another molecule and is re-oxidized to NAD+
23.
Gibbs free energy
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Just as in mechanics, where the decrease in potential energy is defined as maximum useful work that can be performed, similarly different potentials have different meanings. The Gibbs energy is also the potential that is minimized when a system reaches chemical equilibrium at constant pressure and temperature. Its derivative with respect to the coordinate of the system vanishes at the equilibrium point. As such, a reduction in G is a condition for the spontaneity of processes at constant pressure and temperature. The Gibbs free energy, originally called available energy, was developed in the 1870s by the American scientist Josiah Willard Gibbs. The initial state of the body, according to Gibbs, is supposed to be such that the body can be made to pass from it to states of dissipated energy by reversible processes. In his 1876 magnum opus On the Equilibrium of Heterogeneous Substances, according to the second law of thermodynamics, for systems reacting at STP, there is a general natural tendency to achieve a minimum of the Gibbs free energy. A quantitative measure of the favorability of a reaction at constant temperature and pressure is the change ΔG in Gibbs free energy that is caused by the reaction. As a necessary condition for the reaction to occur at constant temperature and pressure, ΔG must be smaller than the non-PV work, ΔG equals the maximum amount of non-PV work that can be performed as a result of the chemical reaction for the case of reversible process. The equation can be seen from the perspective of the system taken together with its surroundings. First assume that the reaction at constant temperature and pressure is the only one that is occurring. Then the entropy released or absorbed by the system equals the entropy that the environment must absorb or release, the reaction will only be allowed if the total entropy change of the universe is zero or positive. This is reflected in a negative ΔG, and the reaction is called exergonic, if we couple reactions, then an otherwise endergonic chemical reaction can be made to happen. In traditional use, the term free was included in Gibbs free energy to mean available in the form of useful work, the characterization becomes more precise if we add the qualification that it is the energy available for non-volume work. However, a number of books and journal articles do not include the attachment free. This is the result of a 1988 IUPAC meeting to set unified terminologies for the scientific community. This standard, however, has not yet been universally adopted. Further, Gibbs stated, In this description, as used by Gibbs, ε refers to the energy of the body, η refers to the entropy of the body
24.
Catalysis
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Catalysis is the increase in the rate of a chemical reaction due to the participation of an additional substance called a catalyst. In most cases, reactions occur faster with a catalyst because they require less activation energy, furthermore, since they are not consumed in the catalyzed reaction, catalysts can continue to act repeatedly. Often only tiny amounts are required in principle, in the presence of a catalyst, less free energy is required to reach the transition state, but the total free energy from reactants to products does not change. A catalyst may participate in multiple chemical transformations, the effect of a catalyst may vary due to the presence of other substances known as inhibitors or poisons or promoters. Catalyzed reactions have an activation energy than the corresponding uncatalyzed reaction, resulting in a higher reaction rate at the same temperature. However, the mechanics of catalysis is complex. Usually, the catalyst participates in this slowest step, and rates are limited by amount of catalyst, in heterogeneous catalysis, the diffusion of reagents to the surface and diffusion of products from the surface can be rate determining. A nanomaterial-based catalyst is an example of a heterogeneous catalyst, analogous events associated with substrate binding and product dissociation apply to homogeneous catalysts. Although catalysts are not consumed by the reaction itself, they may be inhibited, deactivated, in heterogeneous catalysis, typical secondary processes include coking where the catalyst becomes covered by polymeric side products. Additionally, heterogeneous catalysts can dissolve into the solution in a system or sublimate in a solid–gas system. The production of most industrially important chemicals involves catalysis, similarly, most biochemically significant processes are catalysed. Research into catalysis is a field in applied science and involves many areas of chemistry, notably organometallic chemistry. Catalysis is relevant to aspects of environmental science, e. g. the catalytic converter in automobiles. Many transition metals and transition metal complexes are used in catalysis as well, Catalysts called enzymes are important in biology. A catalyst works by providing a reaction pathway to the reaction product. The rate of the reaction is increased as this route has a lower activation energy than the reaction route not mediated by the catalyst. The disproportionation of hydrogen peroxide creates water and oxygen, as shown below,2 H2O2 →2 H2O + O2 This reaction is preferable in the sense that the reaction products are more stable than the starting material, though the uncatalysed reaction is slow. In fact, the decomposition of hydrogen peroxide is so slow that hydrogen peroxide solutions are commercially available and this reaction is strongly affected by catalysts such as manganese dioxide, or the enzyme peroxidase in organisms
25.
Enzyme
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Enzymes /ˈɛnzaɪmz/ are macromolecular biological catalysts. Enzymes accelerate, or catalyze, chemical reactions, the molecules at the beginning of the process upon which enzymes may act are called substrates and the enzyme converts these into different molecules, called products. Almost all metabolic processes in the cell need enzymes in order to occur at rates fast enough to sustain life, the set of enzymes made in a cell determines which metabolic pathways occur in that cell. The study of enzymes is called enzymology, enzymes are known to catalyze more than 5,000 biochemical reaction types. Most enzymes are proteins, although a few are catalytic RNA molecules, enzymes specificity comes from their unique three-dimensional structures. Like all catalysts, enzymes increase the rate of a reaction by lowering its activation energy, some enzymes can make their conversion of substrate to product occur many millions of times faster. An extreme example is orotidine 5-phosphate decarboxylase, which allows a reaction that would take millions of years to occur in milliseconds. Chemically, enzymes are like any catalyst and are not consumed in chemical reactions, enzymes differ from most other catalysts by being much more specific. Enzyme activity can be affected by other molecules, inhibitors are molecules that decrease enzyme activity, many drugs and poisons are enzyme inhibitors. An enzymes activity decreases markedly outside its optimal temperature and pH, some enzymes are used commercially, for example, in the synthesis of antibiotics. French chemist Anselme Payen was the first to discover an enzyme, diastase and he wrote that alcoholic fermentation is an act correlated with the life and organization of the yeast cells, not with the death or putrefaction of the cells. In 1877, German physiologist Wilhelm Kühne first used the term enzyme, the word enzyme was used later to refer to nonliving substances such as pepsin, and the word ferment was used to refer to chemical activity produced by living organisms. Eduard Buchner submitted his first paper on the study of yeast extracts in 1897, in a series of experiments at the University of Berlin, he found that sugar was fermented by yeast extracts even when there were no living yeast cells in the mixture. He named the enzyme that brought about the fermentation of sucrose zymase, in 1907, he received the Nobel Prize in Chemistry for his discovery of cell-free fermentation. Following Buchners example, enzymes are usually named according to the reaction they carry out, the biochemical identity of enzymes was still unknown in the early 1900s. Sumner showed that the enzyme urease was a protein and crystallized it. These three scientists were awarded the 1946 Nobel Prize in Chemistry, the discovery that enzymes could be crystallized eventually allowed their structures to be solved by x-ray crystallography. This high-resolution structure of lysozyme marked the beginning of the field of structural biology, an enzymes name is often derived from its substrate or the chemical reaction it catalyzes, with the word ending in -ase
26.
Hexokinase
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A hexokinase is an enzyme that phosphorylates hexoses, forming hexose phosphate. In most organisms, glucose is the most important substrate of hexokinases, scientists have discovered and demonstrated that Hexokinase posses the ability to transfer a inorganic phosphate group from ATP to a substrate. Hexokinases should not be confused with glucokinase, which is an isoform of hexokinase. While other hexokinases are capable of phosphorylating several hexoses, glucokinase acts with a 50-fold lower substrate affinity and its only hexose substrate is glucose. Genes that encode hexokinase have been discovered in every domain of life, and exist among a variety of species range from bacteria, yeast. They are categorized as actin fold proteins, sharing a common ATP binding site core that is surrounded by more variable sequences which determine substrate affinities, several hexokinase isoforms or isozymes that provide different functions can occur in a single species. Phosphorylation of a such as glucose often limits it to a number of intracellular metabolic processes. This is because phosphorylated hexoses are charged, and thus difficult to transport out of a cell. Most bacterial hexokinases are approximately 50 kD in size, multicellular organisms including plants and animals often have more than one hexokinase isoform. Most are about 100 kD in size and consist of two halves, which share much sequence homology and this suggests an evolutionary origin by duplication and fusion of a 50kD ancestral hexokinase similar to those of bacteria. There are four important mammalian hexokinase isozymes that vary in subcellular locations and kinetics with respect to different substrates and conditions, and physiological function. They are designated hexokinases I, II, III, and IV or hexokinases A, B, C, and D. Hexokinases I, II, Hexokinases I and II follow Michaelis-Menten kinetics at physiologic concentrations of substrates. All three are strongly inhibited by their product, glucose-6-phosphate, molecular weights are around 100 kD. Each consists of two similar 50kD halves, but only in hexokinase II do both halves have functional active sites, Hexokinase I/A is found in all mammalian tissues, and is considered a housekeeping enzyme, unaffected by most physiological, hormonal, and metabolic changes. Hexokinase II/B constitutes the principal regulated isoform in many types and is increased in many cancers. It is the hexokinase found in muscle and heart, Hexokinase II is also located at the mitochondria outer membrane so it can have direct access to ATP. Hexokinase III/C is substrate-inhibited by glucose at physiologic concentrations, little is known about the regulatory characteristics of this isoform. Mammalian hexokinase IV, also referred to as glucokinase, differs from other hexokinases in kinetics, the location of the phosphorylation on a subcellular level occurs when glucokinase translocates between the cytoplasm and nucleus of liver cells
27.
Committed step
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In enzymology, the committed step is an effectively irreversible enzymatic reaction that occurs at a branch point during the biosynthesis of some molecules. As the name implies, after this step, the molecules are committed to the pathway, the first committed step should not be confused with the rate-determining step, which is the slowest step in a reaction or pathway. However, it is sometimes the case that the first committed step is in fact the rate-determining step as well, metabolic pathways require tight regulation so that the proper compounds get produced in the proper amounts. Often, the first committed step is regulated by processes such as feedback inhibition and activation, such regulation ensures that pathway intermediates do not accumulate, a situation that can be wasteful or even harmful to the cell. Phosphofructokinase 1 catalyzes the first committed step of glycolysis, lpxC catalyzes the first committed step of lipid A biosynthesis. 8-amino-7-oxononanoate synthase catalyzes the first committed step in plant biotin synthesis, murA catalyzes the first committed step of peptidoglycan biosynthesis. Aspartate transcarbamoylase catalyzes the committed step in the biosynthetic pathway in E. coli. The term has also applied to other processes that involve a series of steps. For example, the binding of egg and sperm can be thought of as the first committed step in metazoan fertilization, enzyme catalysis Negative feedback Glycolysis Regulation at Cliffsnotes. com
28.
2-Phosphoglyceric acid
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2-Phosphoglyceric acid, or 2-phosphoglycerate, is a glyceric acid which serves as the substrate in the ninth step of glycolysis. It is catalyzed by enolase into phosphoenolpyruvate, the step in the conversion of glucose to pyruvate. Compound C00197 at KEGG Pathway Database, enzyme 5.4.2.1 at KEGG Pathway Database. Compound C00631 at KEGG Pathway Database, enzyme 4.2.1.11 at KEGG Pathway Database. Compound C00074 at KEGG Pathway Database, click on genes, proteins and metabolites below to link to respective articles
29.
Dihydrolipoyl transacetylase
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Dihydrolipoyl transacetylase is an enzyme component of the multienzyme pyruvate dehydrogenase complex. The pyruvate dehydrogenase complex is responsible for the decarboxylation step that links glycolysis to the citric acid cycle. This involves the transformation of pyruvate from glycolysis into acetyl-CoA which is used in the citric acid cycle to carry out cellular respiration. There are three different enzyme components in the pyruvate dehydrogenase complex, pyruvate dehydrogenase is responsible for the oxidation of pyruvate, dihydrolipoyl transacetylase transfers the acetyl group to coenzyme A, and dihydrolipoyl dehydrogenase regenerates the lipoamide. In humans, dihydrolipoyl transacetylase enzymatic activity resides in the pyruvate dehydrogenase complex component E2 that is encoded by the DLAT gene, the systematic name of this enzyme class is acetyl-CoA, enzyme N6-lysine S-acetyltransferase. Other names in use include, All dihydrolipoyl transacetylases have a unique multidomain structure consisting of,3 lipoyl domains, an interaction domain. Interestingly all the domains are connected by disordered, low complexity linker regions, depending on the species, multiple subunits of dihydrolipoyl transacetylase enzymes can arrange together into either a cubic or dodecahedral shape. The cubic core structure, found in such as Azotobacter vinelandii, is made up of 24 subunits total. The catalytic domains are assembled into trimers with the site located at the subunit interface. The topology of this active site is identical to that of chloramphenicol acetyltransferase. Eight of these trimers are then arranged into a truncated cube. The two main substrates, CoA and the lipoamide, are found at two opposite entrances of a 30 Å long channel which runs between the subunits and forms the catalytic center, CoA enters from the inside of the cube, and the lipoamide enters from the outside. The subunits are arranged in sets of three, similar to the trimers in the cubic shape, with each set making up one of the 20 dodecahedral vertices. Dihydrolipoyl transacetylase participates in the decarboxylation reaction that links glycolysis to the citric acid cycle. The various parts of cellular respiration take place in different parts of the cell, thus pyruvate dehydrogenase complexes are found in the mitochondria of eukaryotes. Pyruvate decarboxylation requires a few cofactors in addition to the enzymes that make up the complex, the first is thiamine pyrophosphate, which is used by pyruvate dehydrogenase to oxidize pyruvate and to form a hydroxyethyl-TPP intermediate. This intermediate is taken up by dihydrolipoyl transacetylase and reacted with a second lipoamide cofactor to generate an acetyl-dihydrolipoyl intermediate and this second intermediate can then be attacked by the nucleophilic sulfur attached to Coenzyme A, and the dihydrolipoamide is released. This results in the production of acetyl CoA, which is the end goal of pyruvate decarboxylation, the dihydrolipoamide is taken up by dihydrolipoyl dehydrogenase, and with the additional cofactors FAD and NAD+, regenerates the original lipoamide
30.
Malic acid
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Malic acid is an organic compound with the molecular formula C4H6O5. It is an acid that is made by all living organisms, contributes to the pleasantly sour taste of fruits. Malic acid has two forms, though only the L-isomer exists naturally. The salts and esters of malic acid are known as malates, the malate anion is an intermediate in the citric acid cycle. L-Malic acid is the naturally occurring form, whereas a mixture of L-, malate plays an important role in biochemistry. In the C4 carbon fixation process, malate is a source of CO2 in the Calvin cycle, in the citric acid cycle, -malate is an intermediate, formed by the addition of an -OH group on the si face of fumarate. It can also be formed from pyruvate via anaplerotic reactions, malate is also synthesized by the carboxylation of phosphoenolpyruvate in the guard cells of plant leaves. Malate, as an anion, often accompanies potassium cations during the uptake of solutes into the guard cells in order to maintain electrical balance in the cell. The accumulation of these solutes within the cell decreases the solute potential, allowing water to enter the cell. Malic acid was first isolated from apple juice by Carl Wilhelm Scheele in 1785, antoine Lavoisier in 1787 proposed the name acide malique, which is derived from the Latin word for apple, mālum—as is its genus name Malus. In German it is named Äpfelsäure after plural or singular of the fruit apple, Malic acid contributes to the sourness of green apples. It is present in grapes and in most wines with concentrations sometimes as high as 5 g/l and it confers a tart taste to wine, although the amount decreases with increasing fruit ripeness. The taste of malic acid is very clear and pure in rhubarb and it is also a component of some artificial vinegar flavors, such as salt and vinegar flavored potato chips. The process of malolactic fermentation converts malic acid to much milder lactic acid, Malic acid occurs naturally in all fruits and many vegetables, and is generated in fruit metabolism. Malic acid, when added to products, is denoted by E number E296. Malic acid is the source of extreme tartness in United States-produced confectionery and it is also used with or in place of the less sour citric acid in sour sweets. These sweets are sometimes labeled with a warning stating that excessive consumption can cause irritation of the mouth and it is approved for use as a food additive in the EU, US and Australia and New Zealand. Malic acid provides 10 kJ of energy per gram during digestion, racemic malic acid is produced industrially by the double hydration of maleic anhydride
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Malate dehydrogenase
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Malate dehydrogenase is an enzyme that reversibly catalyzes the oxidation of malate to oxaloacetate using the reduction of NAD+ to NADH. This reaction is part of metabolic pathways, including the citric acid cycle. Other malate dehydrogenases, which have other EC numbers and catalyze other reactions oxidizing malate, have qualified names like malate dehydrogenase, several isozymes of malate dehydrogenase exist. There are two main isoforms in eukaryotic cells, one is found in the mitochondrial matrix, participating as a key enzyme in the citric acid cycle that catalyzes the oxidation of malate. Humans and most other mammals express the following two malate dehydrogenases, The malate dehydrogenase family contains L-lactate dehydrogenase and L-2-hydroxyisocaproate dehydrogenases, L-lactate dehydrogenases catalyzes the conversion of L-lactate to pyruvate, the last step in anaerobic glycolysis. The N-terminus is a Rossmann NAD-binding fold and the C-terminus is an unusual alpha+beta fold, in most organisms, malate dehydrogenase exists as a homodimeric molecule and is closely related to lactate dehydrogenase in structure. It is a protein molecule with subunits weighing between 30 and 35 kDa. Based on the amino acid sequences, it seems that MDH has diverged into two main groups that closely resemble either mitochondrial isozymes or cytoplasmic/chloroplast isozymes. The amino acid sequences of archaeal MDH are more similar to that of LDH than that of MDH of other organisms and this indicates that there is a possible evolutionary linkage between lactate dehydrogenase and malate dehydrogenase. Each subunit of the malate dehydrogenase dimer has two domains that vary in structure and functionality. A parallel β-sheet structure makes up the NAD+ binding domain, while four β-sheets, the subunits are held together through extensive hydrogen-bonding and hydrophobic interactions. Malate dehydrogenase has also shown to have a mobile loop region that plays a crucial role in the enzymes catalytic activity. Studies have also indicated that this region is highly conserved in malate dehydrogenase. The active site of malate dehydrogenase is a cavity within the protein complex that has specific binding sites for the substrate and its coenzyme. In its active state, MDH undergoes a change that encloses the substrate to minimize solvent exposure. The three residues in particular that comprise a catalytic triad are histidine, aspartate, both of work together as a proton transfer system, and arginines, which secure the substrate. Mechanistically, malate dehydrogenase catalyzes the oxidation of the group of malate by utilizing NAD+ as an electron acceptor. This oxidation step results in the elimination of a proton and an ion from the substrate
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Dihydroxyacetone phosphate
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Dihydroxyacetone phosphate is a biochemical compound involved in many metabolic pathways, including the Calvin cycle in plants and glycolysis. Dihydroxyacetone phosphate lies in the metabolic pathway, and is one of the two products of breakdown of fructose 1, 6-bisphosphate, along with glyceraldehyde 3-phosphate. It is rapidly and reversibly isomerised to glyceraldehyde 3-phosphate, Compound C05378 at KEGG Pathway Database. Enzyme 4.1.2.13 at KEGG Pathway Database, Compound C00111 at KEGG Pathway Database. Compound C00118 at KEGG Pathway Database, the numbering of the carbon atoms indicates the fate of the carbons according to their position in fructose 6-phosphate. Compound C00111 at KEGG Pathway Database. Enzyme 5.3.1.1 at KEGG Pathway Database. Compound C00118 at KEGG Pathway Database, click on genes, proteins and metabolites below to link to respective articles. In the Calvin cycle, DHAP is one of the products of the reduction of 1. It is also used in the synthesis of sedoheptulose 1, 7-bisphosphate and fructose 1, 6-bisphosphate, DHAP is also the product of the dehydrogenation of L-glycerol-3-phosphate, which is part of the entry of glycerol into the glycolytic pathway. Conversely, reduction of glycolysis-derived DHAP to L-glycerol-3-phosphate provides adipose cells with the glycerol backbone they require to synthesize new triglycerides. Both reactions are catalyzed by the enzyme glycerol 3-phosphate dehydrogenase with NAD+/NADH as cofactor, DHAP also has a role in the ether-lipid biosynthesis process in the protozoan parasite Leishmania mexicana
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Pyruvic acid
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Pyruvic acid is the simplest of the alpha-keto acids, with a carboxylic acid and a ketone functional group. Pyruvate, the base, CH3COCOO−, is a key intermediate in several metabolic pathways. Pyruvic acid can be made from glucose through glycolysis, converted back to carbohydrates via gluconeogenesis and it can also be used to construct the amino acid alanine and can be converted into ethanol or lactic acid via fermentation. Pyruvic acid supplies energy to cells through the citric acid cycle when oxygen is present, pyruvic acid is a colorless liquid with a smell similar to that of acetic acid and is miscible with water. It is the output of the metabolism of known as glycolysis. One molecule of glucose breaks down into two molecules of pyruvate, which are used to provide further energy, in one of two ways. Pyruvate is converted into acetyl-coenzyme A, which is the input for a series of reactions known as the Krebs cycle. Pyruvate is also converted to oxaloacetate by an reaction, which replenishes Krebs cycle intermediates, also. These reactions are named after Hans Adolf Krebs, the biochemist awarded the 1953 Nobel Prize for physiology, jointly with Fritz Lipmann, for research into metabolic processes. The cycle is known as the citric acid cycle or tricarboxylic acid cycle. If insufficient oxygen is available, the acid is broken down anaerobically, creating lactate in animals and ethanol in plants, Pyruvate is a key intersection in the network of metabolic pathways. Pyruvate can be converted into carbohydrates via gluconeogenesis, to fatty acids or energy through acetyl-CoA, to the amino acid alanine, therefore, it unites several key metabolic processes. In glycolysis, phosphoenolpyruvate is converted to pyruvate by pyruvate kinase and this reaction is strongly exergonic and irreversible, in gluconeogenesis, it takes two enzymes, pyruvate carboxylase and PEP carboxykinase, to catalyze the reverse transformation of pyruvate to PEP. Compound C00074 at KEGG Pathway Database, enzyme 2.7.1.40 at KEGG Pathway Database. Compound C00022 at KEGG Pathway Database, click on genes, proteins and metabolites below to link to respective articles. Pyruvate decarboxylation by the pyruvate dehydrogenase complex produces acetyl-CoA, carboxylation by pyruvate carboxylase produces oxaloacetate. Transamination by alanine transaminase produces alanine, reduction by lactate dehydrogenase produces lactate. Pyruvate is sold as a supplement, though evidence supporting this use is lacking
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GLUT2
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Glucose transporter 2 also known as solute carrier family 2, member 2 is a transmembrane carrier protein that enables protein facilitated glucose movement across cell membranes. It is the transporter for transfer of glucose between liver and blood, and has a role in renal glucose reabsorption. It is also capable of transporting fructose, unlike GLUT4, it does not rely on insulin for facilitated diffusion. In humans, this protein is encoded by the SLC2A2 gene, GLUT2 is found in cellular membranes of, liver pancreatic β cell hypothalamus basolateral membrane of small intestine and apical GLUT2 is also suggested. Basolateral membrane of renal tubular cells GLUT2 has high capacity for glucose but low affinity and it is a very efficient carrier for glucose. Basolateral GLUT2 in enterocytes also aids in the transport of fructose into the bloodstream through glucose-dependent cotransport, defects in the SLC2A2 gene are associated with a particular type of glycogen storage disease called Fanconi-Bickel syndrome. Maintaining a regulated osmotic balance of sugar concentration between the circulation and the interstitial spaces is critical in some cases of edema including cerebral edema. GLUT2 appears to be important to osmoregulation, and preventing edema-induced stroke, transient ischemic attack or coma. GLUT2 could reasonably be referred to as the glucose transporter or a stress hyperglycemia glucose transporter. Click on genes, proteins and metabolites below to link to respective articles, Glucose transporter Glucose Transporter Type 2 at the US National Library of Medicine Medical Subject Headings
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Enolase 2
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Gamma-enolase, also known as enolase 2 or neuron specific enolase, is an enzyme that in humans is encoded by the ENO2 gene. Gamma-enolase is one of the three enolase isoenzymes found in mammals and this isoenzyme, a homodimer, is found in mature neurons and cells of neuronal origin. A switch from alpha enolase to gamma enolase occurs in tissue during development in rats. Click on genes, proteins and metabolites below to link to respective articles, detection of NSE with antibodies can be used to identify neuronal cells and cells with neuroendocrine differentiation. NSE is produced by small cell carcinomas which are neuroendocrine in origin, NSE is therefore a useful tumor marker for lung cancer patients
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Oxaloacetic acid
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Oxaloacetic acid is a crystalline organic compound with the chemical formula HO2CCCH2CO2H. Oxaloacetic acid, in the form of its conjugate base oxaloacetate, is an intermediate in many processes that occur in animals. It takes part in the gluconeogenesis, urea cycle, glyoxylate cycle, amino acid synthesis, fatty acid synthesis, oxaloacetate forms in several ways in nature. A principal route is upon oxidation of L-malate, catalysed by malate dehydrogenase, malate is also oxidized by succinate dehydrogenase in a slow reaction with the initial product being enol-oxaloacetate. Oxaloacetate can also arise from trans- or de- amination of aspartic acid, oxaloacetate is an intermediate of the citric acid cycle, where it reacts with Acetyl-CoA to form citrate, catalysed by citrate synthase. It is also involved in gluconeogenesis, urea cycle, glyoxylate cycle, amino acid synthesis, oxaloacetate is also a potent inhibitor of Complex II. Gluconeogenesis is a pathway consisting of a series of eleven enzyme-catalyzed reactions. The beginning of this takes place in the mitochondrial matrix. A pyruvate molecule is carboxylated by a pyruvate carboxylase enzyme, activated by a molecule each of ATP and this reaction results in the formation of oxaloacetate. This transformation is needed to transport the molecule out of the mitochondria, once in the cytosol, malate is oxidized to oxaloacetate again using NAD+. Then oxaloacetate remains in the cytosol, where the rest of reactions take place. Oxaloacetate is later decarboxylated and phosphorylated by phosphoenolpyruvate carboxykinase and becomes 2-phosphoenolpyruvate using guanosine triphosphate as phosphate source, glucose is obtained after further downstream processing. The urea cycle is a pathway that results in the formation of urea using two ammonium molecules and one bicarbonate molecule. This route commonly occurs in hepatocytes, the reactions related to the urea cycle produce NADH), and NADH can be produced in two different ways. In the cytosol there are fumarate molecules, fumarate can be transformed into malate by the actions of the enzyme fumarase. Malate is acted on by malate dehydrogenase to become oxaloacetate, producing a molecule of NADH, after that, oxaloacetate will be recycled to aspartate, as transaminases prefer these keto acids over the others. This recycling maintains the flow of nitrogen into the cell, the glyoxylate cycle is a variant of the citric acid cycle. It is a pathway occurring in plants and bacteria utilizing the enzymes isocitrate lyase
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Fructose 1,6-bisphosphatase
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Fructose bisphosphatase is an enzyme that converts fructose-1, 6-bisphosphate to fructose 6-phosphate in gluconeogenesis and the Calvin cycle which are both anabolic pathways. Fructose bisphosphatase catalyses the reverse of the reaction which is catalysed by phosphofructokinase in glycolysis, more specifically, fructose 2, 6-bisphosphate allosterically inhibits fructose 1, 6-bisphosphatase, but activates phosphofructokinase-I. Fructose 1, 6-bisphosphatase is involved in many different metabolic pathways, FBPase requires metal ions for catalysis and the enzyme is potently inhibited by Li+. The fold of fructose-1, 6-bisphosphatase from pig was noted to be identical to that of inositol-1-phosphatase, inositol polyphosphate 1-phosphatase, IMPase and FBPase share a sequence motif which has been shown to bind metal ions and participate in catalysis. This motif is found in the distantly-related fungal, bacterial. Three different groups of FBPases have been identified in eukaryotes and bacteria, none of these groups have been found in archaea so far, though a new group of FBPases which also show inositol monophosphatase activity has recently been identified in archaea. A new group of FBPases is found in archaea and the hyperthermophilic bacterium Aquifex aeolicus. The characterised members of this group show strict substrate specificity for FBP and are suggested to be the true FBPase in these organisms, the arrangement of the catalytic side chains and metal ligands was found to be consistent with the three-metal ion assisted catalysis mechanism proposed for other FBPases. The fructose 1, 6-bisphosphatases found within the Firmicutes do not show any significant sequence similarity to the enzymes from other organisms, the Bacillus subtilis enzyme is inhibited by AMP, though this can be overcome by phosphoenolpyruvate, and is dependent on Mn. Mutants lacking this enzyme are still able to grow on gluconeogenic growth substrates such as malate. Click on genes, proteins and metabolites below to link to respective articles, during hibernation, an animal’s metabolic rate may decrease to around 1/25 of its euthermic resting metabolic rate. Studies have found that FBPase is modified in hibernating animals to be much more sensitive than it is in euthermic animals. In one study, FBPase in the liver of a hibernating bat showed a 75% decrease in Km for its substrate FBP at 5°C than at 37°C, however, in a euthermic bat this decrease was only 25%, demonstrating the difference in temperature sensitivity between hibernating and euthermic bats. During hibernation, respiration also dramatically decreases, resulting in conditions of relative anoxia in the tissues, anoxic conditions inhibit gluconeogenesis, and therefore FBPase, while stimulating glycolysis, and this is another reason for reduced FBPase activity in hibernating animals. In addition to hibernation, there is evidence that FBPase activity varies significantly between warm and cold even for animals that do not hibernate. In rabbits exposed to temperatures, FBPase activity decreased throughout the duration of cold exposure. The mechanism of this FBPase inhibition is thought to be digestion of FBPase by lysosomal proteases, inhibition of FBPase through proteolytic digestion decreases gluconeogenesis relative to glycolysis during cold periods, similar to hibernation. Fructose 1, 6-bisphosphate aldolase is another temperature dependent enzyme that plays an important role in the regulation of glycolysis and gluconeogenesis during hibernation
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G6PC
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Glucose-6-phosphatase, catalytic subunit is an enzyme that in humans is encoded by the G6PC gene. Glucose-6-phosphatase is a membrane protein of the endoplasmic reticulum that catalyzes the hydrolysis of D-glucose 6-phosphate to D-glucose. It is a key enzyme in glucose homeostasis, functioning in gluconeogenesis and glycogenolysis, defects in the enzyme cause glycogen storage disease type I. Click on genes, proteins and metabolites below to link to respective articles, g6PC2 G6PC3 glucose 6-phosphatase glycogen storage disease type I
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GLUT5
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GLUT5 is a fructose transporter expressed on the apical border of enterocytes in the small intestine. GLUT5 allows for fructose to be transported from the lumen into the enterocyte by facilitated diffusion due to fructoses high concentration in the intestinal lumen. GLUT5 is also expressed in muscle, testis, kidney, fat tissue. Fructose malabsorption or Dietary Fructose Intolerance is a disability of the small intestine. In humans the GLUT5 protein is encoded by the SLC2A5 gene, Fructose uptake rate by GLUT5 is significantly affected by diabetes mellitus, hypertension, obesity, fructose malabsorption, and inflammation. However, age-related changes in fructose intake capability are not explained by the rate of expression of GLUT5, the absorption of fructose in the simultaneous presence of glucose is improved, while sorbitol is inhibitory. Click on genes, proteins and metabolites below to link to respective articles, GLUT5 Protein at the US National Library of Medicine Medical Subject Headings
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