Low-carbohydrate diets or carbohydrate-restricted diets are diets that restrict carbohydrate consumption. Foods high in carbohydrates are limited or replaced with foods containing a higher percentage of fats and moderate protein and other foods low in carbohydrates, although other vegetables and fruits are allowed. There is a lack of standardization of how much carbohydrate low-carbohydrate diets must have, this has complicated research. One definition, from the American Academy of Family Physicians, specifies low-carbohydrate diets as having less than 20% carbohydrate content. Low-carbohydrate diets are associated with increased mortality, they can miss out on the health benefits afforded by high-quality carbohydrate such as is found in legumes including grain legumes or pulses, fruit and vegetables. Disadvantages of the diet might include halitosis and constipation, in general the potential adverse effects of the diet are under-researched for more serious possible risks such as for bone health and cancer incidence.
Carbohydrate-restricted diets can be as effective, or marginally more effective, than low-fat diets in helping achieve weight loss in the short term. In the long term, effective weight maintenance depends on calorie restriction, not the ratio of macronutrients in a diet; the hypothesis proposed by diet advocates that carbohydrate causes undue fat accumulation via the medium of insulin, that low-carbohydrate diets have a "metabolic advantage", has been falsified by experiment. It is not clear. Carbohydrate-restricted diets are no more effective than a conventional healthy diet in preventing the onset of type 2 diabetes, but for people with type 2 diabetes they are a viable option for losing weight or helping with glycemic control. There is little evidence; the American Diabetes Association recommends that people with diabetes should adopt a healthy diet, rather than a diet focused on carbohydrate or other macronutrients. An extreme form of low-carbohydrate diet – the ketogenic diet – is established as a medical diet for treating epilepsy.
Through celebrity endorsement it has become a popular weight-loss fad diet, but there is no evidence of any distinctive benefit for this purpose, it had a number of side effects. The British Dietetic Association named it one of the "top 5 worst celeb diets to avoid in 2018"; the macronutrient ratios of low-carbohydrate diets are not standardized. As of 2018 the conflicting definitions of "low-carbohydrate" diets have complicated research into the subject; the American Academy of Family Physicians defines low-carbohydrate diets as diets that restrict carbohydrate intake to 20 to 60 grams per day less than 20% of caloric intake. A 2016 review of low-carbohydrate diets classified diets with 50g of carbohydrate per day as "very low" and diets with 40% of calories from carbohydrates as "mild" low-carbohydrate diets. In a 2015 review Richard D. Feinman and colleagues proposed that a low carbohydrate diet had less that 10% caloric intake from carbohydrate, a low carbohydrate diet less than 26%, a medium carbohydrate diet less than 45%, a high carbohydrate diet more than 45%.
Both high- and low-carbohydrate diets are associated with increased mortality. The optimal proportion of carbohydrate in a diet for health is thought to be 50-55%. There is evidence that the quality, rather than the quantity, of carbohydrate in a diet is important for health, that high-fiber slow-digesting carbohydrate-rich foods are healthful while highly-refined and sugary foods are less so. People choosing diet for health conditions should have their diet tailored to their individual requirements. For people with metabolic conditions, in general a diet with 40-50% high-quality carbohydrate is compatible with what is scientifically established to be a healthy diet; some fruits may contain high concentrations of sugar, most are water and not calorie-dense. Thus, in absolute terms sweet fruits and berries do not represent a significant source of carbohydrates in their natural form, typically contain a good deal of fiber which attenuates the absorption of sugar in the gut. Most vegetables are low- or moderate-carbohydrate foods.
Some vegetables, such as potatoes, carrots and rice are high in starch. Most low-carbohydrate diet plans accommodate vegetables such as broccoli, kale, cucumbers, cauliflower and most green-leafy vegetables. In 2004, the Canadian government ruled that foods sold in Canada could not be marketed with reduced or eliminated carbohydrate content as a selling point, because reduced carbohydrate content was not determined to be a health benefit; the government ruled that existing "low carb" and "no carb" packaging would have to be phased out by 2006. The National Academy of Medicine recommends a minimum intake of 130 g of carbohydrate per day; the FAO and WHO recommend that the majority of dietary energy come from carbohydrates. Low-carbohydrate diets are not an option recommended in the 2015-2020 edition of Dietary Guidelines for Americans, which instead recommends a low fat diet. Carbohydrate has been wrongly accused of being a uniquely "fattening" macronutrient, misleading many dieters into compro
Ethers are a class of organic compounds that contain an ether group—an oxygen atom connected to two alkyl or aryl groups. They have the general formula R -- O -- R ′, where R ′ represent the alkyl or aryl groups. Ethers can again be classified into two varieties: if the alkyl groups are the same on both sides of the oxygen atom it is a simple or symmetrical ether, whereas if they are different, the ethers are called mixed or unsymmetrical ethers. A typical example of the first group is the solvent and anesthetic diethyl ether referred to as "ether". Ethers are common in organic chemistry and more prevalent in biochemistry, as they are common linkages in carbohydrates and lignin. Ethers feature C–O–C linkage defined by a bond angle of about 110° and C–O distances of about 140 pm; the barrier to rotation about the C–O bonds is low. The bonding of oxygen in ethers and water is similar. In the language of valence bond theory, the hybridization at oxygen is sp3. Oxygen is more electronegative than carbon, thus the hydrogens alpha to ethers are more acidic than in simple hydrocarbons.
They are far less acidic than hydrogens alpha to carbonyl groups, however. Depending on the groups at R and R′, ethers are classified into two types:Simple ethers or symmetrical ethers. Mixed ethers or asymmetrical ethers. In the IUPAC nomenclature system, ethers are named using the general formula "alkoxyalkane", for example CH3–CH2–O–CH3 is methoxyethane. If the ether is part of a more-complex molecule, it is described as an alkoxy substituent, so –OCH3 would be considered a "methoxy-" group; the simpler alkyl radical is written in front, so CH3–O–CH2CH3 would be given as methoxyethane. IUPAC rules are not followed for simple ethers; the trivial names for simple ethers are a composite of the two substituents followed by "ether". For example, ethyl methyl ether, diphenylether; as for other organic compounds common ethers acquired names before rules for nomenclature were formalized. Diethyl ether is called "ether", but was once called sweet oil of vitriol. Methyl phenyl ether is anisole, because it was found in aniseed.
The aromatic ethers include furans. Acetals are another class of ethers with characteristic properties. Polyethers are compounds with more than one ether group; the crown ethers are examples of small polyethers. Some toxins produced by dinoflagellates such as brevetoxin and ciguatoxin are large and are known as cyclic or ladder polyethers. Polyether refers to polymers which contain the ether functional group in their main chain; the term glycol is reserved for low to medium range molar mass polymer when the nature of the end-group, a hydroxyl group, still matters. The term "oxide" or other terms are used for high molar mass polymer when end-groups no longer affect polymer properties; the phenyl ether polymers are a class of aromatic polyethers containing aromatic cycles in their main chain: Polyphenyl ether and Poly. Many classes of compounds with C–O–C linkages are not considered ethers: Esters, carboxylic acid anhydrides. Ether molecules cannot form hydrogen bonds with each other, resulting in low boiling points compared to those of the analogous alcohols.
The difference in the boiling points of the ethers and their isomeric alcohols becomes lower as the carbon chains become longer, as the van der Waals interactions of the extended carbon chain dominates over the presence of hydrogen bonding. Ethers are polar; the C–O–C bond angle in the functional group is about 110°, the C–O dipoles do not cancel out. Ethers are more polar than alkenes but not as polar as alcohols, esters, or amides of comparable structure; the presence of two lone pairs of electrons on the oxygen atoms makes hydrogen bonding with water molecules possible. Cyclic ethers such as tetrahydrofuran and 1,4-dioxane are miscible in water because of the more exposed oxygen atom for hydrogen bonding as compared to linear aliphatic ethers. Other properties are: The lower ethers are volatile and flammable. Lower ethers act as anaesthetics. Ethers are good organic solvents. Simple ethers are tasteless. Ethers are quite stable chemical compounds which do not react with bases, active metals, dilute acids, oxidising agents, reducing agents.
They are of low chemical reactivity, but they are more reactive than alkanes. Epoxides and acetals are unrepresentative classes of ethers and are discussed in separate articles. Important reactions are listed below. Although ethers resist hydrolysis, their polar bonds are cloven by mineral acids such as hydrobromic acid and hydroiodic acid. Hydrogen chloride cleaves ethers only slowly. Methyl ethers afford methyl halides: ROCH3 + HBr → CH3Br + ROHThese reactions proceed via onium intermediates, i.e. +Br−. Some ethers undergo rapid cleavage with boron tribromide to give the alkyl bromide. Depending on the substituents, some ethers can be cloven with a variety of reagents, e.g. strong base. When stored in the presence of air or oxygen, ethers tend to form explosive peroxides, such as diethyl ether peroxide; the reaction is accelerated by light, metal catalysts, aldehydes. In addition to avoiding storage conditions to form peroxides, it is recommended, when an ether is used as a solvent, not to distill it to dryness, as any peroxides that may have formed, being less volatil
Acid dissociation constant
An acid dissociation constant, Ka, is a quantitative measure of the strength of an acid in solution. It is the equilibrium constant for a chemical reaction known as dissociation in the context of acid–base reactions. K a =; the chemical species HA, A−, H+ are said to be in equilibrium when their concentrations do not change with the passing of time, because both forward and backward reactions are occurring at the same fast rate. The chemical equation for acid dissociation can be written symbolically as: HA ↽ − − ⇀ A − + H + where HA is a generic acid that dissociates into A−, the conjugate base of the acid and a hydrogen ion, H+, it is implicit in this definition that the quotient of activity coefficients, Γ, Γ = γ A − γ H + γ A H is a constant that can be ignored in a given set of experimental conditions. For many practical purposes it is more convenient to discuss the logarithmic constant, pKa p K a = − log 10 The more positive the value of pKa, the smaller the extent of dissociation at any given pH —that is, the weaker the acid.
A weak acid has a pKa value in the approximate range −2 to 12 in water. For a buffer solution consisting of a weak acid and its conjugate base, pKa can be expressed as: p K a = pH − log 10 The pKa for a weak monoprotic acid is conveniently determined by potentiometric titration with a strong base to the equivalence point and taking the pH value measured at one-half this volume as being equal to pKa; that is because at this half equivalence point, the number of moles of strong base added is one-half the number of moles of weak acid present, while the concentrations of the conjugate base and the remaining weak acid are the same. Acids with a pKa value of less than about −2 are said to be strong acids. In water, the dissociation of a strong acid in dilute solutions is complete such that the final concentration of the undissociated acid final is low. Consider a strong monoprotic acid, such as HCl; because of their 1:1 ratio, the final concentration of the conjugate base, final, is taken to be equal to the concentration of the hydronium ion, which can be directly measured by a pH meter.
For strong monoprotic acids like HCl, final and are both nearly equal to the initial concentration of initial placed into solution. With conventional acid-base titration methods it is difficult to measure the pH of a strong acid solution and, hence, to determine the or final, with a sufficient number of significant figures to and compute the low values encountered for final, which can be as low as 10-9 mol per liter for some strong acids. Furthermore, if 100% dissociation is assumed, final is zero and the fraction within parenthesis in the equation above becomes undefined; because the second expression on the right-hand side of the above equation is therefore indeterminable by conventional titration methods, the entire equation is not as useful a means of experimentally measuring pKa for strong acids as it is for weak acids. However, pKa and/or Ka values for strong acids can be estimated by theoretical means, such as computing gas phase dissociation constants and using Gibbs free energies of solvation for the molecular anions.
It is possible to use spectroscopy in some cases to determine the ratio of the concentrations of the conjugate base produced and the undissociated acid. For example, the Raman spectra of dilute nitric acid solutions contain signals of the nitrate ion and as the solutions become more concentrated signals of undissociated nitric acid molecules emerge; the acid dissociation constant for an acid is a direct consequence of the underlying thermodynamics of the dissociation reaction. The value of the pKa changes with temperature and can be understood qualitatively based on Le Châtelier's principle: when the reaction is endothermic, Ka increases and pKa decreases with
A hydrogen bond is a electrostatic force of attraction between a hydrogen atom, covalently bound to a more electronegative atom or group the second-row elements nitrogen, oxygen, or fluorine —the hydrogen bond donor —and another electronegative atom bearing a lone pair of electrons—the hydrogen bond acceptor. Such an interacting system is denoted Dn–H···Ac, where the solid line denotes a covalent bond, the dotted line indicates the hydrogen bond. There is general agreement that there is a minor covalent component to hydrogen bonding for moderate to strong hydrogen bonds, although the importance of covalency in hydrogen bonding is debated. At the opposite end of the scale, there is no clear boundary between a weak hydrogen bond and a van der Waals interaction. Weaker hydrogen bonds are known for hydrogen atoms bound to elements such as chlorine; the hydrogen bond is responsible for many of the anomalous physical and chemical properties of compounds of N, O, F. Hydrogen bonds can be intramolecular.
Depending on the nature of the donor and acceptor atoms which constitute the bond, their geometry, environment, the energy of a hydrogen bond can vary between 1 and 40 kcal/mol. This makes them somewhat stronger than a van der Waals interaction, weaker than covalent or ionic bonds; this type of bond can occur in inorganic molecules such as water and in organic molecules like DNA and proteins. Intermolecular hydrogen bonding is responsible for the high boiling point of water compared to the other group 16 hydrides that have much weaker hydrogen bonds. Intramolecular hydrogen bonding is responsible for the secondary and tertiary structures of proteins and nucleic acids, it plays an important role in the structure of polymers, both synthetic and natural. It was recognized that there are many examples of weaker hydrogen bonding involving donor Dn other than N, O, or F and/or acceptor Ac with close to or the same electronegativity as hydrogen. Though they are quite weak, they are ubiquitous and are recognized as important control elements in receptor-ligand interactions in medicinal chemistry or intra-/intermolecular interactions in materials sciences.
Thus, there is a trend of gradual broadening for the definition of hydrogen bonding. In 2011, an IUPAC Task Group recommended a modern evidence-based definition of hydrogen bonding, published in the IUPAC journal Pure and Applied Chemistry; this definition specifies: The hydrogen bond is an attractive interaction between a hydrogen atom from a molecule or a molecular fragment X–H in which X is more electronegative than H, an atom or a group of atoms in the same or a different molecule, in which there is evidence of bond formation. Most introductory textbooks still restrict the definition of hydrogen bond to the "classical" type of hydrogen bond characterized in the opening paragraph. A hydrogen atom attached to a electronegative atom is the hydrogen bond donor. C-H bonds only participate in hydrogen bonding when the carbon atom is bound to electronegative substituents, as is the case in chloroform, CHCl3. In a hydrogen bond, the electronegative atom not covalently attached to the hydrogen is named proton acceptor, whereas the one covalently bound to the hydrogen is named the proton donor.
In the donor molecule, the H center is protic. The donor is a Lewis base. Hydrogen bonds are represented as H · · · Y system. Liquids that display hydrogen bonding are called associated liquids; the hydrogen bond is described as an electrostatic dipole-dipole interaction. However, it has some features of covalent bonding: it is directional and strong, produces interatomic distances shorter than the sum of the van der Waals radii, involves a limited number of interaction partners, which can be interpreted as a type of valence; these covalent features are more substantial when acceptors bind hydrogens from more electronegative donors. Hydrogen bonds can vary in strength from weak to strong. Typical enthalpies in vapor include: F−H···:F, illustrated uniquely by HF2−, bifluoride O−H···:N, illustrated water-ammonia O−H···:O, illustrated water-water, alcohol-alcohol N−H···:N, illustrated by ammonia-ammonia N−H···:O, illustrated water-amide HO−H···:OH+3 The strength of intermolecular hydrogen bonds is most evaluated by measurements of equilibria between molecules containing donor and/or acceptor units, most in solution.
The strength of intramolecular hydrogen bonds can be studied with equilibria between conformers with and without hydrogen bonds. The most important method for the identification of hydrogen bonds in complicated molecules is crystallography, sometimes NMR-spectroscopy. Structural details, in particular distances between donor and acceptor which are smaller than the sum of the van der Waals radii can be taken as indication of the hydrogen bond strength. One scheme gives the following somewhat arbitrary classification: those that are 15 to 40 kcal/mol, 5 to 15 kcal/mol, >0 to 5 kcal/mol are considered strong, moder
The mitochondrion is a double-membrane-bound organelle found in most eukaryotic organisms. Some cells in some multicellular organisms may, lack them. A number of unicellular organisms, such as microsporidia and diplomonads, have reduced or transformed their mitochondria into other structures. To date, only one eukaryote, Monocercomonoides, is known to have lost its mitochondria; the word mitochondrion comes from the Greek μίτος, mitos, "thread", χονδρίον, chondrion, "granule" or "grain-like". Mitochondria generate most of the cell's supply of adenosine triphosphate, used as a source of chemical energy. A mitochondrion was thus termed the powerhouse of the cell. Mitochondria are between 0.75 and 3 μm in diameter but vary in size and structure. Unless stained, they are not visible. In addition to supplying cellular energy, mitochondria are involved in other tasks, such as signaling, cellular differentiation, cell death, as well as maintaining control of the cell cycle and cell growth. Mitochondrial biogenesis is in turn temporally coordinated with these cellular processes.
Mitochondria have been implicated in several human diseases, including mitochondrial disorders, cardiac dysfunction, heart failure and autism. The number of mitochondria in a cell can vary by organism and cell type. For instance, red blood cells have no mitochondria, whereas liver cells can have more than 2000; the organelle is composed of compartments. These compartments or regions include the outer membrane, the intermembrane space, the inner membrane, the cristae and matrix. Although most of a cell's DNA is contained in the cell nucleus, the mitochondrion has its own independent genome that shows substantial similarity to bacterial genomes. Mitochondrial proteins vary depending on the species. In humans, 615 distinct types of protein have been identified from cardiac mitochondria, whereas in rats, 940 proteins have been reported; the mitochondrial proteome is thought to be dynamically regulated. The first observations of intracellular structures that represented mitochondria were published in the 1840s.
Richard Altmann, in 1890, established them as cell organelles and called them "bioblasts". The term "mitochondria" was coined by Carl Benda in 1898. Leonor Michaelis discovered that Janus green can be used as a supravital stain for mitochondria in 1900. In 1904, Friedrich Meves, made the first recorded observation of mitochondria in plants in cells of the white waterlily, Nymphaea alba and in 1908, along with Claudius Regaud, suggested that they contain proteins and lipids. Benjamin F. Kingsbury, in 1912, first related them with cell respiration, but exclusively based on morphological observations. In 1913, particles from extracts of guinea-pig liver were linked to respiration by Otto Heinrich Warburg, which he called "grana". Warburg and Heinrich Otto Wieland, who had postulated a similar particle mechanism, disagreed on the chemical nature of the respiration, it was not until 1925, when David Keilin discovered cytochromes, that the respiratory chain was described. In 1939, experiments using minced muscle cells demonstrated that cellular respiration using one oxygen atom can form two adenosine triphosphate molecules, and, in 1941, the concept of the phosphate bonds of ATP being a form of energy in cellular metabolism was developed by Fritz Albert Lipmann.
In the following years, the mechanism behind cellular respiration was further elaborated, although its link to the mitochondria was not known. The introduction of tissue fractionation by Albert Claude allowed mitochondria to be isolated from other cell fractions and biochemical analysis to be conducted on them alone. In 1946, he concluded that cytochrome oxidase and other enzymes responsible for the respiratory chain were isolated to the mitochondria. Eugene Kennedy and Albert Lehninger discovered in 1948 that mitochondria are the site of oxidative phosphorylation in eukaryotes. Over time, the fractionation method was further developed, improving the quality of the mitochondria isolated, other elements of cell respiration were determined to occur in the mitochondria; the first high-resolution electron micrographs appeared in 1952, replacing the Janus Green stains as the preferred way of visualising the mitochondria. This led to a more detailed analysis of the structure of the mitochondria, including confirmation that they were surrounded by a membrane.
It showed a second membrane inside the mitochondria that folded up in ridges dividing up the inner chamber and that the size and shape of the mitochondria varied from cell to cell. The popular term "powerhouse of the cell" was coined by Philip Siekevitz in 1957. In 1967, it was discovered. In 1968, methods were developed for mapping the mitochondrial genes, with the genetic and physical map of yeast mitochondrial DNA being completed in 1976. There are two hypotheses about the origin of mitochondria: autogenous; the endosymbiotic hypothesis suggests that mitochondria were prokaryotic cells, capable of implementing oxidative mechanisms that were not possible for eukaryotic cells. In the autogenous hypothesis, mitochondria were born by splitting off a portion of DNA from the nucleus of the eukaryotic cell at the time of divergence with the prokaryotes. Since mitochondria have many features in common with bacteria, the endosymbiotic hypothesis is more accepted. A mitochondrion contains DNA, which i
Thiolases known as acetyl-coenzyme A acetyltransferases, are enzymes which convert two units of acetyl-CoA to acetoacetyl CoA in the mevalonate pathway. Thiolases are ubiquitous enzymes that have key roles in many vital biochemical pathways, including the beta oxidation pathway of fatty acid degradation and various biosynthetic pathways. Members of the thiolase family can be divided into two broad categories: degradative thiolases and biosynthetic thiolases; these two different types of thiolase are found both in eukaryotes and in prokaryotes: acetoacetyl-CoA thiolase and 3-ketoacyl-CoA thiolase. 3-ketoacyl-CoA thiolase has a broad chain-length specificity for its substrates and is involved in degradative pathways such as fatty acid beta-oxidation. Acetoacetyl-CoA thiolase is specific for the thiolysis of acetoacetyl-CoA and involved in biosynthetic pathways such as beta-hydroxybutyric acid synthesis or steroid biogenesis; the formation of a carbon–carbon bond is a key step in the biosynthetic pathways by which fatty acids and polyketide are made.
The thiolase superfamily enzymes catalyse the carbon–carbon-bond formation via a thioester-dependent Claisen condensation reaction mechanism. Thiolases are a family of evolutionarily related enzymes. Two different types of thiolase are found both in eukaryotes and in prokaryotes: acetoacetyl-CoA thiolase and 3-ketoacyl-CoA thiolase. 3-ketoacyl-CoA thiolase has a broad chain-length specificity for its substrates and is involved in degradative pathways such as fatty acid beta-oxidation. Acetoacetyl-CoA thiolase is specific for the thiolysis of acetoacetyl-CoA and involved in biosynthetic pathways such as poly beta-hydroxybutyrate synthesis or steroid biogenesis. In eukaryotes, there are two forms of 3-ketoacyl-CoA thiolase: one located in the mitochondrion and the other in peroxisomes. There are two conserved cysteine residues important for thiolase activity; the first located in the N-terminal section of the enzymes is involved in the formation of an acyl-enzyme intermediate. Mammalian nonspecific lipid-transfer protein is a protein which seems to exist in two different forms: a 14 Kd protein and a larger 58 Kd protein.
The former is involved in lipid transport. The C-terminal part of SCP-x is identical to SCP-2 while the N-terminal portion is evolutionary related to thiolases. Thioesters are more reactive than oxygen esters and are common intermediates in fatty-acid metabolism; these thioesters are made by conjugating the fatty acid with the free SH group of the pantetheine moiety of either coenzyme A or acyl carrier protein. All thiolases, whether they are biosynthetic or degradative in vivo, preferentially catalyze the degradation of 3-ketoacyl-CoA to form acetyl-CoA and a shortened acyl-CoA species, but are capable of catalyzing the reverse Claisen condensation reaction, it is well established from studies on the biosynthetic thiolase from Z. ramigera that the thiolase reaction occurs in two steps and follows ping-pong kinetics. In the first step of both the degradative and biosynthetic reactions, the nucleophilic Cys89 attacks the acyl-CoA substrate,leading to the formation of a covalent acyl-CoA intermediate.
In the second step, the addition of CoA or acetyl-CoA to the acyl–enzyme intermediate triggers the release of the product from the enzyme. Each of the tetrahedral reaction intermediates that occur during transfer of an acetyl group to and from the nucleophilic cysteine have been observed in X-ray crystal structures of biosynthetic thiolase from A. fumigatus. Most enzymes of the thiolase super family are dimers. However, monomers have not been observed. Tetrameters are observed only in the thiolase subfamily and, in these cases, the dimers have dimerized to become tetramers; the crystal structure of the tetrameric biosynthetic thiolase from Zoogloea ramigera has been determined at 2.0 Å resolution. The structure contains a striking and novel ‘cage-like’ tetramerization motif, which allows for some hinge motion of the two tight dimers with respect to each other; the enzyme tetramer is acetylated at Cys89 and has a CoA molecule bound in each of its active-site pockets. In eukaryotic cells in mammalian cells, thiolases exhibit diversity in intracellular localization related to their metabolic functions as well as in substrate specificity.
For example, they contribute to fatty-acid β-oxidation in peroxisomes and mitochondria, ketone body metabolism in mitochondria, the early steps of mevalonate pathway in peroxisomes and cytoplasm. In addition to biochemical investigations, analyses of genetic disorders have made clear the basis of their functions. Genetic studies have started to disclose the physiological functions of thiolases in the yeast Saccharomyces cerevisiae. Thiolase is of central importance in key enzymatic pathways such as fatty-acid and polyketide synthesis; the detailed understanding of its structural biology is of great medical relevance, for example, for a better understanding of the diseases caused by genetic deficiencies of these enzymes and for the development of new antibiotics. Harnessing the complicated catalytic versatility of the polyketide synthases for the synthesis of biologically and medically relevant natural products is an important future perspective of the studies of the enzy
Simplified molecular-input line-entry system
The simplified molecular-input line-entry system is a specification in the 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 been extended. In 2007, an open standard called. Other linear notations include the Wiswesser line notation, ROSDAL, SYBYL Line Notation; the original SMILES specification was initiated by David Weininger at the USEPA Mid-Continent Ecology Division Laboratory in Duluth in the 1980s. Acknowledged for their parts in the early development were "Gilman Veith and Rose Russo and Albert Leo and Corwin Hansch for supporting the work, Arthur Weininger and Jeremy Scofield for assistance in programming the system." The Environmental Protection Agency funded the initial project to develop SMILES. It has since been modified and extended by others, most notably by Daylight Chemical Information Systems.
In 2007, an open 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 considered to have the advantage of being more human-readable than InChI; the term SMILES refers to a line notation for encoding molecular structures and specific instances should be called SMILES strings. However, the term SMILES is commonly used to refer to both a single SMILES string and a number of SMILES strings; the terms "canonical" and "isomeric" can lead to some confusion when applied to SMILES. The terms are not mutually exclusive. A number of 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; this SMILES is unique for each structure, although dependent on the canonicalization algorithm used to generate it, is termed the canonical SMILES.
These algorithms first convert the SMILES to an internal representation of the molecular structure. Various algorithms for generating canonical SMILES have been developed and include those by Daylight Chemical Information Systems, OpenEye Scientific Software, MEDIT, Chemical Computing Group, MolSoft LLC, the Chemistry Development Kit. A common application of canonical SMILES is indexing and ensuring uniqueness of molecules in a database; the original paper that described the CANGEN algorithm claimed to generate unique SMILES strings for graphs representing molecules, but the algorithm fails for a number of simple cases and cannot be considered a correct method for representing a graph canonically. There is 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, double bond geometry; these are structural features that cannot be specified by connectivity alone and SMILES which encode this information are termed isomeric SMILES.
A notable feature of these rules is. The term isomeric SMILES is applied to SMILES in which isotopes are specified. In terms of a graph-based computational procedure, SMILES is a string obtained by printing the symbol nodes encountered in a depth-first tree traversal of a chemical graph; the chemical graph is first trimmed to remove hydrogen atoms and cycles are broken to turn it into a spanning tree. Where cycles have been broken, numeric suffix labels are included to indicate the connected nodes. Parentheses are used to indicate points of branching on the tree; the resultant SMILES form depends on the choices: of the bonds chosen to break cycles, of the starting atom used for the depth-first traversal, of the order in which branches are listed when encountered. Atoms are represented by the standard abbreviation of the chemical elements, in square brackets, such as for gold. Brackets may be omitted in the common case of atoms which: are in the "organic subset" of B, C, N, O, P, S, F, Cl, Br, or I, have no formal charge, have the number of hydrogens attached implied by the SMILES valence model, are the normal isotopes, are not chiral centers.
All other elements must be enclosed in brackets, have charges and hydrogens shown explicitly. For instance, the SMILES for water may be written as either O or. Hydrogen may be written as a separate atom; when brackets are used, the symbol H is added if the atom in brackets is bonded to one or more hydrogen, followed by the number of hydrogen atoms if greater than 1 by the sign + for a positive charge or by - for a negative charge. For example, for ammonium. If there is more than one charge, it is written as digit.