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Shikimic acid

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Shikimic acid , more commonly known as its anionic form shikimate , is a cyclohexene , a cyclitol and a cyclohexanecarboxylic acid . It is an important biochemical metabolite in plants and microorganisms. Its name comes from the Japanese flower shikimi ( シキミ , the Japanese star anise , Illicium anisatum ), from which it was first isolated in 1885 by Johan Fredrik Eykman . The elucidation of its structure was made nearly 50 years later.

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49-414: Phosphoenolpyruvate and erythrose-4-phosphate condense to form 3-deoxy- D -arabinoheptulosonate-7-phosphate (DAHP), in a reaction catalyzed by the enzyme DAHP synthase . DAHP is then transformed to 3-dehydroquinate (DHQ), in a reaction catalyzed by DHQ synthase . Although this reaction requires nicotinamide adenine dinucleotide (NAD) as a cofactor, the enzymic mechanism regenerates it, resulting in

98-419: A plane of symmetry or a center of symmetry is achiral. There are, however, achiral figures lacking both plane and center of symmetry. In terms of point groups , all chiral figures lack an improper axis of rotation (S n ). This means that they cannot contain a center of inversion (i) or a mirror plane (σ). Only figures with a point group designation of C 1 , C n , D n , T, O, or I can be chiral. A knot

147-533: A chiral molecule, the plane of polarization, when viewed along the axis toward the source, will be rotated clockwise (to the right) or anticlockwise (to the left). A right handed rotation is dextrorotary (d); that to the left is levorotary (l). The d- and l-isomers are the same compound but are called enantiomers . An equimolar mixture of the two optical isomers, which is called a racemic mixture , will produce no net rotation of polarized light as it passes through. Left handed molecules have l- prefixed to their names; d-

196-452: A right shoe is different from a left shoe, and clockwise is different from anticlockwise. See for a full mathematical definition. A chiral object and its mirror image are said to be enantiomorphs. The word enantiomorph stems from the Greek ἐναντίος ( enantios ) 'opposite' + μορφή ( morphe ) 'form'. A non-chiral figure is called achiral or amphichiral. The helix (and by extension

245-481: A single enantiomer drug for a better therapeutic value. [1] Such a switching from a racemic drug to an enantiopure drug is called a chiral switch . The naturally occurring plant form of alpha-tocopherol ( vitamin E ) is RRR-α-tocopherol whereas the synthetic form (all-racemic vitamin E, or dl-tocopherol) is equal parts of the stereoisomers RRR, RRS, RSS, SSS, RSR, SRS, SRR, and SSR with progressively decreasing biological equivalency, so that 1.36 mg of dl-tocopherol

294-420: A small minority of species and genera are virtually always sinistral (left-handed). A very few species (for example Amphidromus perversus ) show an equal mixture of dextral and sinistral individuals. In humans, chirality (also referred to as handedness or laterality ) is an attribute of humans defined by their unequal distribution of fine motor skill between the left and right hands . An individual who

343-532: A sphere, cannot be distinguished from the object. A chiral object and its mirror image are called enantiomorphs (Greek, "opposite forms") or, when referring to molecules, enantiomers . A non-chiral object is called achiral (sometimes also amphichiral ) and can be superposed on its mirror image. The term was first used by Lord Kelvin in 1893 in the second Robert Boyle Lecture at the Oxford University Junior Scientific Club which

392-429: A spun string, a screw, a propeller, etc.) and Möbius strip are chiral two-dimensional objects in three-dimensional ambient space. The J, L, S and Z-shaped tetrominoes of the popular video game Tetris also exhibit chirality, but only in a two-dimensional space. Many other familiar objects exhibit the same chiral symmetry of the human body, such as gloves, glasses (sometimes), and shoes. A similar notion of chirality

441-523: Is a biosynthetic intermediate and in general found in very low concentrations. The low isolation yield of shikimic acid from the Chinese star anise is blamed for the 2005 shortage of oseltamivir. Shikimic acid can also be extracted from the seeds of the sweetgum ( Liquidambar styraciflua ) fruit, which is abundant in North America, in yields of around 1.5%. For example, 4 kg (8.8 lb) of sweetgum seeds

490-431: Is a precursor for: Mycosporine-like amino acids are small secondary metabolites produced by organisms that live in environments with high volumes of sunlight, usually marine environments. In the pharmaceutical industry, shikimic acid from the Chinese star anise ( Illicium verum ) is used as a base material for production of oseltamivir ( Tamiflu ). Although shikimic acid is present in most autotrophic organisms, it

539-450: Is a property of asymmetry important in several branches of science. The word chirality is derived from the Greek χείρ ( kheir ), "hand", a familiar chiral object. An object or a system is chiral if it is distinguishable from its mirror image ; that is, it cannot be superposed (not to be confused with superimposed ) onto it. Conversely, a mirror image of an achiral object, such as

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588-402: Is an important intermediate in biochemistry . It has the highest-energy phosphate bond found (−61.9 kJ/mol) in organisms, and is involved in glycolysis and gluconeogenesis . In plants, it is also involved in the biosynthesis of various aromatic compounds, and in carbon fixation ; in bacteria, it is also used as the source of energy for the phosphotransferase system . PEP is formed by

637-420: Is associated with 3d chirality and circular conversion is associated with 2d chirality, both effects have also been observed in structures that are not chiral by themselves. For the observation of these chiral electromagnetic effects, chirality does not have to be an intrinsic property of the material that interacts with the electromagnetic wave. Instead, both effects can also occur when the propagation direction of

686-485: Is associated with directionally asymmetric transmission (reflection and absorption) of circularly polarized waves. 2D-chiral materials, which are also anisotropic and lossy exhibit different total transmission (reflection and absorption) levels for the same circularly polarized wave incident on their front and back. The asymmetric transmission phenomenon arises from different, e.g. left-to-right, circular polarization conversion efficiencies for opposite propagation directions of

735-399: Is because of other contributing factors. Also, for artificial compounds, including medicines, in case of chiral drugs , the two enantiomers sometimes show remarkable difference in effect of their biological actions. Darvon ( dextropropoxyphene ) is a painkiller, whereas its enantiomer, Novrad ( levopropoxyphene ) is an anti-cough agent. In case of penicillamine , the ( S -isomer is used in

784-417: Is called achiral if it can be continuously deformed into its mirror image, otherwise it is called chiral. For example, the unknot and the figure-eight knot are achiral, whereas the trefoil knot is chiral. In physics, chirality may be found in the spin of a particle, where the handedness of the object is determined by the direction in which the particle spins. Not to be confused with helicity , which

833-612: Is considered equivalent to 1.0 mg of d-tocopherol. Macroscopic examples of chirality are found in the plant kingdom, the animal kingdom and all other groups of organisms. A simple example is the coiling direction of any climber plant, which can grow to form either a left- or right-handed helix. In anatomy, chirality is found in the imperfect mirror image symmetry of many kinds of animal bodies. Organisms such as gastropods exhibit chirality in their coiled shells, resulting in an asymmetrical appearance. Over 90% of gastropod species have dextral (right-handed) shells in their coiling, but

882-537: Is considered in knot theory , as explained below. Some chiral three-dimensional objects, such as the helix, can be assigned a right or left handedness, according to the right-hand rule . In geometry , a figure is achiral if and only if its symmetry group contains at least one orientation-reversing isometry. In two dimensions, every figure that possesses an axis of symmetry is achiral, and it can be shown that every bounded achiral figure must have an axis of symmetry. In three dimensions, every figure that possesses

931-409: Is formed from the decarboxylation of oxaloacetate and hydrolysis of one guanosine triphosphate molecule. This reaction is catalyzed by the enzyme phosphoenolpyruvate carboxykinase (PEPCK). This reaction is a rate-limiting step in gluconeogenesis: Click on genes, proteins and metabolites below to link to respective articles. PEP may be used for the synthesis of chorismate through

980-403: Is highly soluble in water and insoluble in nonpolar solvents, and this is why shikimic acid is active only against Gram-positive bacteria , due to outer cell membrane impermeability of Gram-negatives . Phosphoenolpyruvate Phosphoenolpyruvate ( 2-phosphoenolpyruvate , PEP ) is the carboxylic acid derived from the enol of pyruvate and phosphate . It exists as an anion . PEP

1029-487: Is more dexterous with the right hand is called right-handed , and one who is more skilled with the left is said to be left-handed . Chirality is also seen in the study of facial asymmetry and is known as aurofacial asymmetry. According to the Axial Twist theory , vertebrate animals develop into a left-handed chirality. Due to this, the brain is turned around and the heart and bowels are turned by 90°. In

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1078-491: Is most often the cause of chirality in molecules is the presence of an asymmetric carbon atom . The term "chiral" in general is used to describe the object that is non-superposable on its mirror image. In chemistry, chirality usually refers to molecules. Two mirror images of a chiral molecule are called enantiomers or optical isomers . Pairs of enantiomers are often designated as " right- ", "left-handed" or, if they have no bias, "achiral". As polarized light passes through

1127-676: Is needed for fourteen packages of Tamiflu. By comparison, star anise has been reported to yield 3% to 7% shikimic acid. Biosynthetic pathways in E. coli have recently been enhanced to allow the organism to accumulate enough material to be used commercially. A 2010 study released by the University of Maine showed that shikimic acid can also be readily harvested from the needles of several species of pine tree. Protecting groups are more commonly used in small-scale laboratory work and initial development than in industrial production processes because their use adds additional steps and material costs to

1176-444: Is prefixed to right handed molecules. However, this d- and l- notation of distinguishing enantiomers does not say anything about the actual spatial arrangement of the ligands/substituents around the stereogenic center, which is defined as configuration. Another nomenclature system employed to specify configuration is Fischer convention. This is also referred to as the D- and L-system. Here

1225-405: Is responsible for the smell of caraway seed oil, whereas (–)-carvone is responsible for smell of spearmint oil. However, it is a commonly held misconception that (+)-limonene is found in oranges (causing its smell), and (–)-limonene is found in lemons (causing its smell). In 2021, after rigorous experimentation, it was found that all citrus fruits contain only (+)-limonene and the odor difference

1274-470: Is the projection of the spin along the linear momentum of a subatomic particle, chirality is an intrinsic quantum mechanical property, like spin. Although both chirality and helicity can have left-handed or right-handed properties, only in the massless case are they identical. In particular for a massless particle the helicity is the same as the chirality while for an antiparticle they have opposite sign. The handedness in both chirality and helicity relate to

1323-1302: The shikimate pathway . Chorismate may then be metabolized into the aromatic amino acids ( phenylalanine , tryptophan and tyrosine ) and other aromatic compounds. The first step is when Phosphoenolpyruvate and erythrose-4-phosphate react to form 3-deoxy-D-arabinoheptulosonate-7-phosphate (DAHP), in a reaction catalyzed by the enzyme DAHP synthase . In addition, in C 4 plants , PEP serves as an important substrate in carbon fixation . The chemical equation, as catalyzed by phosphoenolpyruvate carboxylase (PEP carboxylase), is: Glucose Hexokinase Glucose 6-phosphate Glucose-6-phosphate isomerase Fructose 6-phosphate Phosphofructokinase-1 Fructose 1,6-bisphosphate Fructose-bisphosphate aldolase Dihydroxyacetone phosphate + Glyceraldehyde 3-phosphate Triosephosphate isomerase 2 × Glyceraldehyde 3-phosphate Glyceraldehyde-3-phosphate dehydrogenase 2 × 1,3-Bisphosphoglycerate Phosphoglycerate kinase 2 × 3-Phosphoglycerate Phosphoglycerate mutase 2 × 2-Phosphoglycerate Phosphopyruvate hydratase ( enolase ) 2 × Phosphoenolpyruvate Pyruvate kinase 2 × Pyruvate Chiral Chirality ( / k aɪ ˈ r æ l ɪ t i / )

1372-628: The E-Z notation. Molecular chirality is of interest because of its application to stereochemistry in inorganic chemistry , organic chemistry , physical chemistry , biochemistry , and supramolecular chemistry . More recent developments in chiral chemistry include the development of chiral inorganic nanoparticles that may have the similar tetrahedral geometry as chiral centers associated with sp3 carbon atoms traditionally associated with chiral compounds, but at larger scale. Helical and other symmetries of chiral nanomaterials were also obtained. All of

1421-527: The action of the enzyme enolase on 2-phosphoglyceric acid . Metabolism of PEP to pyruvic acid by pyruvate kinase (PK) generates adenosine triphosphate (ATP) via substrate-level phosphorylation . ATP is one of the major currencies of chemical energy within cells . Compound C00631 at KEGG Pathway Database. Enzyme 4.2.1.11 at KEGG Pathway Database. Compound C00074 at KEGG Pathway Database. Enzyme 2.7.1.40 at KEGG Pathway Database. Compound C00022 at KEGG Pathway Database. PEP

1470-423: The biosynthesis of aromatic amino acids ( phenylalanine , tyrosine , and tryptophan ). This pathway is not found in animals; therefore, phenylalanine and tryptophan are essential nutrients and must be obtained from the animal's diet. Tyrosine is not essential, as it can be synthesized from phenylalanine, except for individuals unable to hydroxylate phenylalanine to tyrosine . Phenylalanine and tyrosine are

1519-473: The case of the health condition situs inversus totalis , in which all the internal organs are flipped horizontally (i.e. the heart placed slightly to the right instead of the left), chirality poses some problems should the patient require a liver or heart transplant, as these organs are chiral, thus meaning that the blood vessels which supply these organs would need to be rearranged should a normal, non situs inversus ( situs solitus ) organ be required. In

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1568-443: The electromagnetic wave together with the structure of an (achiral) material form a chiral experimental arrangement. This case, where the mutual arrangement of achiral components forms a chiral (experimental) arrangement, is known as extrinsic chirality. Chiral mirrors are a class of metamaterials that reflect circularly polarized light of a certain helicity in a handedness-preserving manner, while absorbing circular polarization of

1617-456: The enzyme 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS). "Roundup Ready" genetically modified crops overcome that inhibition. It occurs in tree fern fronds, a specialty called fiddlehead (furled fronds of a young tree fern in the order Cyatheales , harvested for use as a vegetable). These fronds are edible, but can be roasted to remove shikimic acid. Shikimic acid is also the glycoside part of some hydrolysable tannins . The acid

1666-438: The genetic make up of the organism. From chemical level (molecular scale), biological systems show extreme stereospecificity in synthesis, uptake, sensing, metabolic processing. A living system usually deals with two enantiomers of the same compound in drastically different ways. In biology, homochirality is a common property of amino acids and carbohydrates . The chiral protein-making amino acids , which are translated through

1715-521: The incident wave and therefore the effect is referred to as circular conversion dichroism. Like the twist of a 2d-chiral pattern appears reversed for opposite directions of observation, 2d-chiral materials have interchanged properties for left-handed and right-handed circularly polarized waves that are incident on their front and back. In particular left-handed and right-handed circularly polarized waves experience opposite directional transmission (reflection and absorption) asymmetries. While optical activity

1764-453: The known life-forms show specific chiral properties in chemical structures as well as macroscopic anatomy, development and behavior. In any specific organism or evolutionarily related set thereof, individual compounds, organs, or behavior are found in the same single enantiomorphic form. Deviation (having the opposite form) could be found in a small number of chemical compounds, or certain organ or behavior but that variation strictly depends upon

1813-503: The major features of both hands to coincide across all axes. This difference in symmetry becomes obvious if someone attempts to shake the right hand of a person using their left hand, or if a left-handed glove is placed on a right hand. In mathematics, chirality is the property of a figure that is not identical to its mirror image. In mathematics , a figure is chiral (and said to have chirality) if it cannot be mapped to its mirror image by rotations and translations alone. For example,

1862-401: The monocot bloodroot family , the species of the genera Wachendorfia and Barberetta have only individuals that either have the style points to the right or the style pointed to the left, with both morphs appearing within the same populations. This is thought to increase outcrossing and so boost genetic diversity, which in turn may help to survive in a changing environment. Remarkably,

1911-445: The net use of no NAD. DHQ is dehydrated to 3-dehydroshikimic acid by the enzyme 3-dehydroquinate dehydratase , which is reduced to shikimic acid by the enzyme shikimate dehydrogenase , which uses nicotinamide adenine dinucleotide phosphate (NADPH) as a cofactor. The shikimate pathway, named after shikimic acid as important intermediate, is a seven-step metabolic route used by bacteria , fungi , algae , parasites, and plants for

1960-442: The opposite handedness. However, most absorbing chiral mirrors operate only in a narrow frequency band, as limited by the causality principle. Employing a different design methodology that allows undesired waves to pass through instead of absorbing the undesired waveform, chiral mirrors are able to show good broadband performance. A chiral molecule is a type of molecule that has a non-superposable mirror image . The feature that

2009-509: The polarization state of electromagnetic waves in chiral media and can cause a negative index of refraction for waves of one handedness when the effect is sufficiently large. While optical activity occurs in structures that are chiral in three dimensions (such as helices), the concept of chirality can also be applied in two dimensions. 2D-chiral patterns, such as flat spirals, cannot be superposed with their mirror image by translation or rotation in two-dimensional space (a plane). 2D chirality

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2058-524: The precursors used in the phenylpropanoids biosynthesis . The phenylpropanoids are then used to produce the flavonoids , coumarins , tannins and lignin . The first enzyme involved is phenylalanine ammonia-lyase (PAL) that converts L - phenylalanine to trans - cinnamic acid and ammonia . Gallic acid is formed from 3-dehydroshikimate by the action of the enzyme shikimate dehydrogenase to produce 3,5-didehydroshikimate . This latter compound spontaneously rearranges to gallic acid. Shikimic acid

2107-449: The process. However, the availability of a cheap chiral building block can overcome these additional costs, for example, shikimic acid for oseltamivir . Aminoshikimic acid is also an alternative to shikimic acid as a starting material for the synthesis of oseltamivir. Shikimate can be used to synthesise (6 S )-6-fluoroshikimic acid , an antibiotic which inhibits the aromatic biosynthetic pathway. More specifically, glyphosate inhibits

2156-461: The relative configuration is assigned with reference to D-(+)-Glyceraldehyde and L-(−)-Glyceraldehyde, being taken as standard. Fischer convention is widely used in sugar chemistry and for α-amino acids. Due to the drawbacks of Fischer convention, it is almost entirely replaced by Cahn-Ingold-Prelog convention , also known as the sequence rule or R and S nomenclature. This was further extended to assign absolute configuration to cis-trans isomers with

2205-480: The ribosome from genetic coding, occur in the L form. However, D -amino acids are also found in nature. The monosaccharides (carbohydrate-units) are commonly found in D -configuration. DNA double helix is chiral (as any kind of helix is chiral), and B-form of DNA shows a right-handed turn. Sometimes, when two enantiomers of a compound are found in organisms, they significantly differ in their taste, smell and other biological actions. For example,(+)- Carvone

2254-454: The rotation of a particle while it proceeds in linear motion with reference to the human hands. The thumb of the hand points towards the direction of linear motion whilst the fingers curl into the palm, representing the direction of rotation of the particle (i.e. clockwise and counterclockwise). Depending on the linear and rotational motion, the particle can either be defined by left-handedness or right-handedness. A symmetry transformation between

2303-458: The treatment of primary chronic arthritis, whereas the ( R )-isomer has no therapeutic effect, as well as being highly toxic. In some cases, the less therapeutically active enantiomer can cause side effects. For example, ( S -naproxen is an analgesic but the ( R -isomer causes renal problems. In such situations where one of the enantiomers of a racemic drug is active and the other partner has undesirable or toxic effect one may switch from racemate to

2352-785: The two is called parity . Invariance under parity by a Dirac fermion is called chiral symmetry . Electromagnetic waves can have handedness associated with their polarization . Polarization of an electromagnetic wave is the property that describes the orientation , i.e., the time-varying direction and amplitude , of the electric field vector . For example, the electric field vectors of left-handed or right-handed circularly polarized waves form helices of opposite handedness in space. Circularly polarized waves of opposite handedness propagate through chiral media at different speeds ( circular birefringence ) and with different losses ( circular dichroism ). Both phenomena are jointly known as optical activity. Circular birefringence causes rotation of

2401-413: Was published in 1894: I call any geometrical figure, or group of points, 'chiral', and say that it has chirality if its image in a plane mirror, ideally realized, cannot be brought to coincide with itself. Human hands are perhaps the most recognized example of chirality. The left hand is a non-superposable mirror image of the right hand; no matter how the two hands are oriented, it is impossible for all

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