Methyl group
A methyl group is an alkyl derived from methane, containing one carbon atom bonded to three hydrogen atoms — CH3. In formulas, the group is abbreviated Me; such hydrocarbon groups occur in many organic compounds. It is a stable group in most molecules. While the methyl group is part of a larger molecule, it can be found on its own in any of three forms: anion, cation or radical; the anion has the radical seven and the cation six. All three forms are reactive and observed; the methylium cation is otherwise not encountered. Some compounds are considered to be sources of the CH3+ cation, this simplification is used pervasively in organic chemistry. For example, protonation of methanol gives a electrophilic methylating reagent: CH3OH + H+ → CH3+ + H2OSimilarly, methyl iodide and methyl triflate are viewed as the equivalent of the methyl cation because they undergo SN2 reactions by weak nucleophiles; the methanide anion exists only under exotic conditions. It can be produced by electrical discharge in ketene at low pressure and its enthalpy of reaction is determined to be about 252.2±3.3 kJ/mol.
In discussions mechanisms of organic reactions, methyl lithium and related Grignard reagents are considered to be salts of "CH3−". Such reagents are prepared from the methyl halides: 2 M + CH3X → MCH3 + MXwhere M is an alkali metal; the methyl radical has the formula CH3. It exists in dilute gases, but in more concentrated form it dimerizes to ethane, it can be produced by thermal decomposition of only certain compounds those with an -N=N- linkage. The reactivity of a methyl group depends on the adjacent substituents. Methyl groups can be quite unreactive. For example, in organic compounds, the methyl group resists attack by the strongest acids; the oxidation of a methyl group occurs in nature and industry. The oxidation products derived from methyl are CH2OH, CHO, CO2H. For example, permanganate converts a methyl group to a carboxyl group, e.g. the conversion of toluene to benzoic acid. Oxidation of methyl groups gives protons and carbon dioxide, as seen in combustion. Demethylation is a common process, reagents that undergo this reaction are called methylating agents.
Common methylating agents are dimethyl sulfate, methyl iodide, methyl triflate. Methanogenesis, the source of natural gas, arises via a demethylation reaction. Certain methyl groups can be deprotonated. For example, the acidity of the methyl groups in acetone is about 1020 more acidic than methane; the resulting carbanions are key intermediates in many reactions in organic synthesis and biosynthesis. Fatty acids are produced in this way; when placed in benzylic or allylic positions, the strength of the C-H bond is decreased, the reactivity of the methyl group increases. One manifestation of this enhanced reactivity is the photochemical chlorination of the methyl group in toluene to give benzyl chloride. In the special case where one hydrogen is replaced by deuterium and another hydrogen by tritium, the methyl substituent becomes chiral. Methods exist to produce optically pure methyl compounds, e.g. chiral acetic acid. Through the use of chiral methyl groups, the stereochemical course of several biochemical transformations have been analyzed.
A methyl group may rotate around the R—C-axis. This is a free rotation only in the simplest cases like gaseous CClH3. In most molecules, the remainder R breaks the C ∞ symmetry of the R—C-axis and creates a potential V that restricts the free motion of the three protons. For the model case of C2H6 this is discussed under the name ethane barrier. In condensed phases, neighbour molecules contribute to the potential. Methyl group rotation can be experimentally studied using quasielastic neutron scattering. French chemists Jean-Baptiste Dumas and Eugene Peligot, after determining methanol's chemical structure, introduced "methylene" from the Greek methy "wine" and hȳlē "wood, patch of trees" with the intention of highlighting its origins, "alcohol made from wood"; the term "methyl" was derived in about 1840 by back-formation from "methylene", was applied to describe "methyl alcohol". Methyl is the IUPAC nomenclature of organic chemistry term for an alkane molecule, using the prefix "meth-" to indicate the presence of a single carbon
Inflammation
Inflammation is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants, is a protective response involving immune cells, blood vessels, molecular mediators. The function of inflammation is to eliminate the initial cause of cell injury, clear out necrotic cells and tissues damaged from the original insult and the inflammatory process, initiate tissue repair; the five classical signs of inflammation are heat, redness and loss of function. Inflammation is a generic response, therefore it is considered as a mechanism of innate immunity, as compared to adaptive immunity, specific for each pathogen. Too little inflammation could lead to progressive tissue destruction by the harmful stimulus and compromise the survival of the organism. In contrast, chronic inflammation may lead to a host of diseases, such as hay fever, atherosclerosis, rheumatoid arthritis, cancer. Inflammation is therefore closely regulated by the body. Inflammation can be classified as either chronic.
Acute inflammation is the initial response of the body to harmful stimuli and is achieved by the increased movement of plasma and leukocytes from the blood into the injured tissues. A series of biochemical events propagates and matures the inflammatory response, involving the local vascular system, the immune system, various cells within the injured tissue. Prolonged inflammation, known as chronic inflammation, leads to a progressive shift in the type of cells present at the site of inflammation, such as mononuclear cells, is characterized by simultaneous destruction and healing of the tissue from the inflammatory process. Inflammation is not a synonym for infection. Infection describes the interaction between the action of microbial invasion and the reaction of the body's inflammatory response—the two components are considered together when discussing an infection, the word is used to imply a microbial invasive cause for the observed inflammatory reaction. Inflammation on the other hand describes purely the body's immunovascular response, whatever the cause may be.
But because of how the two are correlated, words ending in the suffix -itis are sometimes informally described as referring to infection. For example, the word urethritis means only "urethral inflammation", but clinical health care providers discuss urethritis as a urethral infection because urethral microbial invasion is the most common cause of urethritis, it is useful to differentiate inflammation and infection because there are typical situations in pathology and medical diagnosis where inflammation is not driven by microbial invasion – for example, trauma and autoimmune diseases including type III hypersensitivity. Conversely, there is pathology where microbial invasion does not cause the classic inflammatory response – for example, parasitosis or eosinophilia. Acute inflammation is a short-term process appearing within a few minutes or hours and begins to cease upon the removal of the injurious stimulus, it involves a coordinated and systemic mobilization response locally of various immune and neurological mediators of acute inflammation.
In a normal healthy response, it becomes activated, clears the pathogen and begins a repair process and ceases. It is characterized by five cardinal signs:An acronym that may be used to remember the key symptoms is "PRISH", for pain, immobility and heat; the traditional names for signs of inflammation come from Latin: Dolor Calor Rubor Tumor Functio laesa The first four were described by Celsus, while loss of function was added by Galen. However, the addition of this fifth sign has been ascribed to Thomas Sydenham and Virchow. Redness and heat are due to increased blood flow at body core temperature to the inflamed site. Loss of function has multiple causes. Acute inflammation of the lung does not cause pain unless the inflammation involves the parietal pleura, which does have pain-sensitive nerve endings; the process of acute inflammation is initiated by resident immune cells present in the involved tissue resident macrophages, dendritic cells, Kupffer cells and mast cells. These cells possess surface receptors known as pattern recognition receptors, which recognize two subclasses of molecules: pathogen-associated molecular patterns and damage-associated molecular patterns.
PAMPs are compounds that are associated with various pathogens, but which are distinguishable from host molecules. DAMPs are compounds that are associated with host-related cell damage. At the onset of an infection, burn, or other injuries, these cells undergo activation and release inflammatory mediators responsible for the clinical signs of inflammation. Vasodilation and its resulting increased blood flow causes increased heat. Increased permeability of the blood vessels results in an exudation of plasma proteins and fluid into the tissue, which manifests itself as swelling; some of the released mediators such as bradykinin increase the sensitivity to pain. The mediator molecules alter the blood vessels to
Amino acid
Amino acids are organic compounds containing amine and carboxyl functional groups, along with a side chain specific to each amino acid. The key elements of an amino acid are carbon, hydrogen and nitrogen, although other elements are found in the side chains of certain amino acids. About 500 occurring amino acids are known and can be classified in many ways, they can be classified according to the core structural functional groups' locations as alpha-, beta-, gamma- or delta- amino acids. In the form of proteins, amino acid residues form the second-largest component of human muscles and other tissues. Beyond their role as residues in proteins, amino acids participate in a number of processes such as neurotransmitter transport and biosynthesis. In biochemistry, amino acids having both the amine and the carboxylic acid groups attached to the first carbon atom have particular importance, they are known as α-amino acids. They include the 22 proteinogenic amino acids, which combine into peptide chains to form the building-blocks of a vast array of proteins.
These are all L-stereoisomers, although a few D-amino acids occur in bacterial envelopes, as a neuromodulator, in some antibiotics. Twenty of the proteinogenic amino acids are encoded directly by triplet codons in the genetic code and are known as "standard" amino acids; the other two are selenocysteine, pyrrolysine. Pyrrolysine and selenocysteine are encoded via variant codons. N-formylmethionine is considered as a form of methionine rather than as a separate proteinogenic amino acid. Codon–tRNA combinations not found in nature can be used to "expand" the genetic code and form novel proteins known as alloproteins incorporating non-proteinogenic amino acids. Many important proteinogenic and non-proteinogenic amino acids have biological functions. For example, in the human brain and gamma-amino-butyric acid are the main excitatory and inhibitory neurotransmitters. Hydroxyproline, a major component of the connective tissue collagen, is synthesised from proline. Glycine is a biosynthetic precursor to porphyrins used in red blood cells.
Carnitine is used in lipid transport. Nine proteinogenic amino acids are called "essential" for humans because they cannot be produced from other compounds by the human body and so must be taken in as food. Others may be conditionally essential for medical conditions. Essential amino acids may differ between species; because of their biological significance, amino acids are important in nutrition and are used in nutritional supplements, fertilizers and food technology. Industrial uses include the production of drugs, biodegradable plastics, chiral catalysts; the first few amino acids were discovered in the early 19th century. In 1806, French chemists Louis-Nicolas Vauquelin and Pierre Jean Robiquet isolated a compound in asparagus, subsequently named asparagine, the first amino acid to be discovered. Cystine was discovered in 1810, although its monomer, remained undiscovered until 1884. Glycine and leucine were discovered in 1820; the last of the 20 common amino acids to be discovered was threonine in 1935 by William Cumming Rose, who determined the essential amino acids and established the minimum daily requirements of all amino acids for optimal growth.
The unity of the chemical category was recognized by Wurtz in 1865, but he gave no particular name to it. Usage of the term "amino acid" in the English language is from 1898, while the German term, Aminosäure, was used earlier. Proteins were found to yield amino acids after enzymatic acid hydrolysis. In 1902, Emil Fischer and Franz Hofmeister independently proposed that proteins are formed from many amino acids, whereby bonds are formed between the amino group of one amino acid with the carboxyl group of another, resulting in a linear structure that Fischer termed "peptide". In the structure shown at the top of the page, R represents a side chain specific to each amino acid; the carbon atom next to the carboxyl group is called the α–carbon. Amino acids containing an amino group bonded directly to the alpha carbon are referred to as alpha amino acids; these include amino acids such as proline which contain secondary amines, which used to be referred to as "imino acids". The alpha amino acids are the most common form found in nature, but only when occurring in the L-isomer.
The alpha carbon is a chiral carbon atom, with the exception of glycine which has two indistinguishable hydrogen atoms on the alpha carbon. Therefore, all alpha amino acids but glycine can exist in either of two enantiomers, called L or D amino acids, which are mirror images of each other. While L-amino acids represent all of the amino acids found in proteins during translation in the ribosome, D-amin
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
Cystathionine gamma-lyase
Cystathionine gamma-lyase is an enzyme which breaks down cystathionine into cysteine, α-ketobutyrate, ammonia. Pyridoxal phosphate is a prosthetic group of this enzyme. Cystathionine gamma-lyase catalyses the following elimination reactions: L-homoserine to form H2O, NH3 and 2-oxobutanoate L-cystine, producing thiocysteine, pyruvate and NH3 L-cysteine producing pyruvate, NH3 and H2SIn some bacteria and mammals, including humans, this enzyme takes part in generating hydrogen sulfide. Hydrogen sulfide is one of a few gases, discovered to have a role in cell signaling in the body. Cystathionase uses pyridoxal phosphate to facilitate the cleavage of the sulfur-gamma carbon bond of cystathionine, resulting in the release of cysteine. Afterwards the external ketimine is hydrolyzed; the lysine residue reforms the internal aldimine by kicking off the ammonia leaving group. The amino group on cystathionine is deprotonated and undergoes a nucleophilic attack of the internal aldimine. An additional deprotonation by a general base results in the formation of the external aldimine and removal of the lysine residue.
The basic lysine residue is able to deprotonate the alpha carbon, pushing electron density into the nitrogen of the pyridine ring. Pyridoxal phosphate is necessary to stabilize this carbanionic intermediate; the beta carbon is deprotonated, creating an alpha-beta unsaturation and pushing a lone pair onto the aldimine nitrogen. To reform the aldimine, this lone pair pushes back down, cleaving the sulfur-gamma carbon bond, resulting in the release of cysteine. A pyridoxamine derivative of vinyl glyoxylate remains after the gamma elimination; the lone pair from the pyridine nitrogen pushes electron density to the gamma carbon, protonated by lysine. Lysine attacks the external aldimine, pushing electron density to the beta carbon, protonated by a general acid; the imine is hydrolyzed to release α-ketobutyrate. Deprotonation of the lysine residue causes ammonia to leave, thus completing the catalytic cycle. Cystathionine gamma lyase shows gamma-synthase activity depending on the concentrations of reactants present.
The mechanisms are the same. In the gamma synthase mechanism, the gamma carbon is attacked by a sulfur nucleophile, resulting in the formation of a new sulfur-gamma carbon bond. Cystathionine gamma-lyase is a member of the Cys/Met metabolism PLP-dependent enzymes family. Other members include cystathionine gamma synthase, cystathionine beta lyase, methionine gamma lyase, it is a member of the broader aspartate aminotransferase family. Like many other PLP-dependent enzymes, cystathionine gamma-lyase is a tetramer with D2 symmetry. Pyridoxal phosphate is bound in the active site by Lys212. Cysteine is the rate-limiting substrate in the synthetic pathway for glutathione in the eye. Glutathione is an antioxidant. Cystathionase is a target for reactive oxygen species, thus as cystathionase is oxidized, its activity decreases, causing a decrease in cysteine and, in turn, glutathione in the eye, leading to a decrease in antioxidant availability, causing a further decrease in cystathionase activity. Deficiencies in cystathionase activity have been shown to contribute to glutathione depletion in patients with cancer and AIDS.
Mutations and deficiencies in cystathionase are associated with cystathioninuria. The mutations T67I and Q240E weaken the enzyme's affinity for pyridoxal phosphate, the co-factor vital to enzymatic function. Low levels of H2S have been associated with hypertension in mice. Excessive levels of H2S, due to increased activity of cystathionase, are associated with endotoxemia, acute pancreatitis, hemorrhagic shock, diabetes mellitus. Propargylglycine and β-cyanoalanine are two irreversible inhibitors of cystathionase used to treat elevated H2S levels. Mechanistically, the amino group of propargylglycine attacks the aldimine to form an external aldimine; the β position of the alkyne is deprotonated to form the allene, attacked by the phenol of Tyr114. The internal aldimine can regenerate, but the newly created vinyl ether sterically hinders the active site, blocking cysteine from attacking pyridoxal phosphate. H2S decreases transcription of cystathionase at concentrations between 10 and 80μM. However, transcription is increased by concentrations near 120μM, inhibited at concentrations in excess of 160μM.
Cysteine metabolism Cystathionine+gamma-lyase at the US National Library of Medicine Medical Subject Headings
Partition coefficient
In the physical sciences, a partition coefficient or distribution coefficient is the ratio of concentrations of a compound in a mixture of two immiscible phases at equilibrium. This ratio is therefore a measure of the difference in solubility of the compound in these two phases; the partition coefficient refers to the concentration ratio of un-ionized species of compound, whereas the distribution coefficient refers to the concentration ratio of all species of the compound. In the chemical and pharmaceutical sciences, both phases are solvents. Most one of the solvents is water, while the second is hydrophobic, such as 1-octanol. Hence the partition coefficient measures how hydrophobic a chemical substance is. Partition coefficients are useful in estimating the distribution of drugs within the body. Hydrophobic drugs with high octanol/water partition coefficients are distributed to hydrophobic areas such as lipid bilayers of cells. Conversely, hydrophilic drugs are found in aqueous regions such as blood serum.
If one of the solvents is a gas and the other a liquid, a gas/liquid partition coefficient can be determined. For example, the blood/gas partition coefficient of a general anesthetic measures how the anesthetic passes from gas to blood. Partition coefficients can be defined when one of the phases is solid, for instance, when one phase is a molten metal and the second is a solid metal, or when both phases are solids; the partitioning of a substance into a solid results in a solid solution. Partition coefficients can be measured experimentally in various ways or estimated by calculation based on a variety of methods. Despite formal recommendation to the contrary, the term partition coefficient remains the predominantly used term in the scientific literature. In contrast, the IUPAC recommends that the title term no longer be used, that it be replaced with more specific terms. For example, partition constant, defined as where KD is the process equilibrium constant, represents the concentration of solute A being tested, "org" and "aq" refer to the organic and aqueous phases respectively.
The IUPAC further recommends "partition ratio" for cases where transfer activity coefficients can be determined, "distribution ratio" for the ratio of total analytical concentrations of a solute between phases, regardless of chemical form. The partition coefficient, abbreviated P, is defined as a particular ratio of the concentrations of a solute between the two solvents for un-ionized solutes, the logarithm of the ratio is thus log P; when one of the solvents is water and the other is a non-polar solvent the log P value is a measure of lipophilicity or hydrophobicity. The defined precedent is for the lipophilic and hydrophilic phase types to always be in the numerator and denominator respectively. To a first approximation, the non-polar phase in such experiments is dominated by the un-ionized form of the solute, electrically neutral, though this may not be true for the aqueous phase. To measure the partition coefficient of ionizable solutes, the pH of the aqueous phase is adjusted such that the predominant form of the compound in solution is the un-ionized, or its measurement at another pH of interest requires consideration of all species, un-ionized and ionized.
A corresponding partition coefficient for ionizable compounds, abbreviated log P I, is derived for cases where there are dominant ionized forms of the molecule, such that one must consider partition of all forms, ionized and un-ionized, between the two phases. M is used to indicate the number of ionized forms. For instance, for an octanol–water partition, it is log P oct/wat I = log . To distinguish between this and the standard, un-ionized, partition coefficient, the un-ionized is assigned the symbol log P0, such that the indexed log P oct/wat I expression for ionized solutes becomes an extension of this, into the range of values I > 0. The distribution co
S-adenosylmethionine synthetase enzyme
S-adenosylmethionine synthetase is an enzyme that creates S-adenosylmethionine by reacting methionine and ATP. AdoMet is a methyl donor for transmethylation, it gives away its methyl group and is the propylamino donor in polyamine biosynthesis. S-adenosylmethionine synthesis can be considered the rate-limiting step of the methionine cycle; as a methyl donor SAM allows DNA methylation. Once DNA is methylated, it switches the genes off and therefore, S-adenosylmethionine can be considered to control gene expression. SAM is involved in gene transcription, cell proliferation, production of secondary metabolites. Hence SAM synthetase is fast becoming a drug target, in particular for the following diseases: depression, vacuolar myelopathy, liver injury, osteoarthritis, as a potential cancer chemopreventive agent; this article discusses the protein domains that make up the SAM synthetase enzyme and how these domains contribute to its function. More this article explores the shared pseudo-3-fold symmetry that makes the domains well-adapted to their functions.
This enzyme catalyses the following chemical reaction ATP + L-methionine + H2O ⇌ phosphate + diphosphate + S-adenosyl-L-methionine A computational comparative analysis of vertebrate genome sequences have identified a cluster of 6 conserved hairpin motifs in the 3'UTR of the MAT2A messenger RNA transcript. The predicted hairpins have strong evolutionary conservation and 3 of the predicted RNA structures have been confirmed by in-line probing analysis. No structural changes were observed for any of the hairpins in the presence of metabolites SAM, S-adenosylhomocysteine or L-Methioninine, they are proposed to be involved in transcript stability and their functionality is under investigation. The S-adenosylmethionine synthetase enzyme is found in every organism bar parasites which obtain AdoMet from their host. Isoenzymes are found in bacteria, budding yeast and in mammalian mitochondria. Most MATs are homo-oligomers and the majority are tetramers; the monomers are organised into three domains formed by nonconsecutive stretches of the sequence, the subunits interact through a large flat hydrophobic surface to form the dimers.
In molecular biology the protein domain S-adenosylmethionine synthetase N terminal domain is found at the N-terminal of the enzyme. The N terminal domain is well conserved across different species; this may be due to its important function in cation binding. The residues involved in methionine binding are found in the N-terminal domain; the N terminal region contains four beta strands. The precise function of the central domain has not been elucidated, but it is thought to be important in aiding catalysis; the central region contains four beta strands. In molecular biology, the protein domain S-adenosylmethionine synthetase, C-terminal domain refers to the C terminus of the S-adenosylmethionine synthetase The function of the C-terminal domain has been experimentally determined as being important for cytoplasmic localisation; the residues are scattered along the C-terminal domain sequence however once the protein folds, they position themselves together. The C-terminal domains contains four beta-strands.
Methionine+adenosyltransferase at the US National Library of Medicine Medical Subject Headings EC 2.5.1.6
verify (what is 
?)
