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| Names | |
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| IUPAC name myo-Inositol | |
| Systematic IUPAC name (1R,2S,3r,4R,5S,6s)-Cyclohexane-1,2,3,4,5,6-hexol | |
| Other names cis-1,2,3,5-trans-4,6-Cyclohexanehexol Cyclohexanehexol Mouse antialopecia factor Nucite Phaseomannite Phaseomannitol Rat antispectacled eye factor Scyllite(for the isomerscyllo-inositol) Vitamin B8 | |
| Identifiers | |
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3D model (JSmol) | |
| ChEBI | |
| ChEMBL | |
| ChemSpider |
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| ECHA InfoCard | 100.027.295 |
| KEGG |
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| UNII | |
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| Properties | |
| C6H12O6 | |
| Molar mass | 180.16 g/mol |
| Density | 1.752 g/cm3 |
| Melting point | 225 to 227 °C (437 to 441 °F; 498 to 500 K) |
| Thermochemistry[2] | |
Std enthalpy of formation(ΔfH⦵298) | −1329.3 kJ/mol |
Std enthalpy of combustion(ΔcH⦵298) | −2747 kJ/mol |
| Pharmacology | |
| A11HA07 (WHO) | |
| Hazards | |
| NFPA 704 (fire diamond) | |
| Flash point | 143 °C (289 °F; 416 K) |
Except where otherwise noted, data are given for materials in theirstandard state (at 25 °C [77 °F], 100 kPa). | |
Inbiochemistry,medicine, and related sciences,inositol generally refers tomyo-inositol (formerlymeso-inositol), the most importantstereoisomer of thechemical compoundcyclohexane-1,2,3,4,5,6-hexol. Itsformula isC6H12O6; the molecule has a ring of sixcarbon atoms, each with anhydrogen atom and ahydroxyl group (–OH). Inmyo-inositol, two of the hydroxyls, neither adjacent nor opposite, lie above the respective hydrogens relative to the mean plane of the ring.
The compound is acarbohydrate, specifically asugar alcohol (as distinct fromaldoses likeglucose) with half thesweetness ofsucrose (table sugar). It is one of the most ancient components of living beings with multiple functions in eukaryotes, including structural lipids andsecondary messengers.[3] A human kidney makes about two grams per day fromglucose, but other tissues synthesize it too. The highest concentration is in the brain, where it plays an important role in making otherneurotransmitters and somesteroid hormones bind to their receptors.[4] In other tissues, it mediates cell signal transduction in response to a variety ofhormones,neurotransmitters, and growth factors and participates inosmoregulation.[5] In most mammalian cells the concentrations ofmyo-inositol are 5 to 500 times greater inside cells than outside them.[6]
A 2023 meta-analysis found that inositol is a safe and effective treatment in the management ofpolycystic ovary syndrome (PCOS).[7] However, there is only evidence of very low quality for its efficacy in increasing fertility for IVF in women with PCOS.[8]
The other naturally occurring stereoisomers of cyclohexane-1,2,3,4,5,6-hexol arescyllo-,muco-,D-chiro-,L-chiro-, andneo-inositol, although they occur in minimal quantities compared tomyo-inositol. The other possible isomers areallo-,epi-, andcis-inositol.
myo-Inositol was first isolated from muscle extracts by Johanes Joseph Scherer (1814–1869) in 1850.[3] It was formerly calledmeso-inositol to distinguish it from thechiro- isomers. However, since all other isomers are meso (non-chiral) compounds, the namemyo-inositol is now preferred (myo- being amedical prefix for "muscle").
Inositol was once considered a member of thevitamin B complex, namelyvitamin B8 before the discovery that it is made naturally in the human body, and therefore cannot be avitamin oressential nutrient.[9]
myo-Inositol is ameso compound, meaning it isoptically inactive because it has aplane of symmetry.[10] It is a white crystalline powder, relatively stable in the air. It is highly soluble in water, slightly soluble inglacial acetic acid,ethanol,glycol, andglycerin, but insoluble inchloroform andether.[3]
In its most stableconformation, themyo-inositol isomer assumes thechair conformation, which moves the maximum number of hydroxyls to the equatorial position, where they are farthest apart from each other. In this conformation, the naturalmyo isomer has a structure in which five of the sixhydroxyls (the first, third, fourth, fifth, and sixth) areequatorial, whereas the second hydroxyl group isaxial.[11]
myo-Inositol plays an important role as the structural basis for a number ofsecondary messengers ineukaryoticcells, the variousinositol phosphates. In addition, inositol serves as an important component of the structural lipidsphosphatidylinositol (PI) and its various phosphates, thephosphatidylinositol phosphate (PIP) lipids.
In humans,myo-Inositol issynthesizedde novo butD-chiro-inositol is not.[6]myo-Inositol is synthesized fromglucose 6-phosphate (G6P) in two steps. First, G6P isisomerised by aninositol-3-phosphate synthase enzyme (for example,ISYNA1) tomyo-inositol 1-phosphate, which is then dephosphorylated by aninositol monophosphatase enzyme (for example,IMPA1) to give freemyo-inositol. In humans, most inositol is synthesized in the kidneys, followed by testicles, typically in amounts of a few grams per day.[5]
At the peripheral level,myo-inositol is converted toD-chiro-inositol by a specific epimerase. Only a minor fraction ofmyo-inositol is converted intoD-chiro-inositol.[6] The activity of this epimerase is insulin dependent, causing a reduction ofD-chiro-inositol in muscle, fat, and liver when there isinsulin resistance.[12][6]D-chiro-inositol reduces the conversion of testosterone to estrogen, thereby increases the levels of testosterone and worsening PCOS.[6]
Inositol hexaphosphate, also calledphytic acid or IP6, is aphytochemical and the principal storage form ofphosphorus in manyplanttissues, especiallybran andseed.[13] Phosphorus and inositol in phytate form are not generallybioavailable to non-ruminant animals because these animals lack the digestiveenzymephytase required to remove the phosphate groups. Ruminants readily digest phytate because of the phytase produced by microorganisms in therumen.[14] Moreover, phytic acid alsochelates important minerals such ascalcium,magnesium,iron, andzinc, making them unabsorbable, and contributing to mineral deficiencies in people whose diets rely highly on bran and seeds for their mineral intake, such as occurs indeveloping countries.[15][16]
Inositol penta- (IP5), tetra- (IP4), and triphosphate (IP3) are also called "phytates".
Inositol or its phosphates and associated lipids are found in many foods, in particular fruit, especiallycantaloupe andoranges.[17] In plants, the hexaphosphate of inositol,phytic acid or its salts, the phytates, serve as phosphate stores in seed, for example in nuts and beans.[18] Phytic acid also occurs incereals with highbran content. Phytate is, however, not directlybioavailable to humans in the diet, since it is not digestible. Some food preparation techniques partly break down phytates to change this. However, inositol in the form ofphospholipids, as found in certain plant-derived substances such aslecithins, is well absorbed and relatively bioavailable.
Inositol, phosphatidylinositol, and some of their mono- and polyphosphates function assecondary messengers in a number of intracellularsignal transduction pathways. They are involved in a number of biological processes, including:
In one important family of pathways,phosphatidylinositol 4,5-bisphosphate (PIP2) is stored in cellular membranes until it is released by any of a number of signalling proteins and transformed into various secondary messengers, for examplediacylglycerol andinositol trisphosphate.[25]
'myo-Inositol has very low toxicity, with a reportedLD50 10,000 mg/kg body weight (oral) in rats.[3]
At the 1936 meeting of theAmerican Chemical Society, professorEdward Bartow of theUniversity of Iowa presented a commercially viable means of extracting large amounts of inositol from the phytic acid naturally present in waste corn. As a possible use for the chemical, he suggested 'inositol nitrate' as a more stable alternative tonitroglycerin.[26] Today, inositol nitrate is used to gelatinizenitrocellulose in many modern explosives and solid rocket propellants.[27]
When plants are exposed to increasing concentrations ofroad salt, the plant cells become dysfunctional and undergoapoptosis, leading to inhibited growth. Inositol pretreatment could reduce these effects.[28]
High doses of inositol may be used to treattrichotillomania (compulsive hair-pulling) and related disorders.[29]
D-chiro-inositol is an important messenger molecule in insulin signaling.[30] Inositol supplementation has been shown to significantly decreasetriglycerides andLDL cholesterol in patients withmetabolic diseases.[30]
myo-Inositol is important forthyroid hormone synthesis.[31] Depletion ofmyo-inositol may predispose to development ofhypothyroidism.[31] Patients with hypothyroidism have a higher demand formyo-inositol than healthy subjects.[31]
Inositol should not be routinely implemented for the management of preterm babies who have or are at a risk ofinfant respiratory distress syndrome (RDS).[32]Myo-inositol helps preventneural tube defects with particular efficacy in combination withfolic acid.[33]
Inositol is considered a safe and effective treatment forpolycystic ovary syndrome (PCOS).[7] It works by increasing insulin sensitivity, which helps to improve ovarian function and reducehyperandrogenism.[34] It is also shown to reduce the risk ofmetabolic disease in women with PCOS.[35] In addition, thanks to its role as FSH second messenger,myo-inositol is effective in restoring FSH/LH ratio and menstrual cycle regularization.[36]myo-Inositol's role as FSH second messenger leads to a correct ovarian follicle maturation and consequently to a higher oocyte quality. Improving the oocyte quality in both women with or without PCOS,myo-inositol can be considered as a possible approach for increasing the chance of success in assisted reproductive technologies.[37][38] In contrast,D-chiro-inositol can impair oocyte quality in a dose-dependent manner.[39] The high level of DCI seems to be related to elevated insulin levels retrieved in about 70% of PCOS women.[40] In this regard, insulin stimulates the irreversible conversion ofmyo-inositol toD-chiro-inositol causing a drastic reduction ofmyo-inositol.myo-Inositol depletion is particularly damaging to ovarian follicles because it is involved in FSH signaling, which is impaired due tomyo-inositol depletion.[12] Recent evidence reports a faster improvement of the metabolic and hormonal parameters when these two isomers are administered in their physiological ratio. The plasmatic ratio ofmyo-inositol andD-chiro-inositol in healthy subjects is 40:1 ofmyo- andD-chiro-inositol respectively.[41] The use of the 40:1 ratio shows the same efficacy ofmyo-inositol alone but in a shorter time. In addition, the physiological ratio does not impair oocyte quality.[42]
The use of inositols in PCOS is gaining more importance, and an efficacy higher than 70% with a strong safety profile is reported. On the other hand, about 30% of patients could show as inositol-resistant.[43] New evidence regarding PCOS aetiopathogenesis describes an alteration in the species and the quantity of each strain characterizing the normal gastrointestinal flora. This alteration could lead to chronic, low-level inflammation and malabsorption.[44] A possible solution could be represented by the combination ofmyo-inositol andα-lactalbumin. This combination shows a synergic effect in increasing myo-inositol absorption.[45] A recent study reported that themyo-inositol and α-lactalbumin combination increasesmyo-inositol plasmatic content in inositol-resistant patients with a relative improvement of hormonal and metabolic parameters.[46]
Inositol has been used as an adulterant orcutting agent for many illegal drugs, such ascocaine,methamphetamine, and sometimesheroin,[47] probably because of its solubility, powdery texture, or reducedsweetness (50%) compared to more common sugars.
Inositol is also used as a stand-infilm prop forcocaine infilmmaking.[48][49]
myo-Inositol is naturally present in a variety of foods, although tables of food composition do not always distinguish betweenlecithin, the relatively bioavailable lipid form and the biounavailable phytate/phosphate form.[17] Foods containing the highest concentrations ofmyo-inositol and its compounds include fruits, beans, grains, and nuts.[17] Fruits in particular, especially oranges and cantaloupe, contain the highest amounts ofmyo-inositol.[50] It is also present in beans, nuts, and grains, however, these contain large amounts ofmyo-inositol in the phytate form, which is not bioavailable without transformation byphytase enzymes.Bacillus subtilis, the microorganism which produces the fermented foodnatto, produces phytase enzymes that may convertphytic acid to a more bioavailable form of inositol polyphosphate in the gut.[51] Additionally,Bacteroides species in the gut secrete vesicles containing an active enzyme which converts the phytate molecule into bioavailable phosphorus and inositol polyphosphate, which is an important signaling molecule in the human body.[52]
myo-Inositol can also be found as an ingredient inenergy drinks,[53] either in conjunction with or as a substitute for glucose.[54]
In humans, myo-inositol is naturally made from glucose-6-phosphate through enzymatic dephosphorylation.[50]
As of 2021, the main industrial process for the production ofmyo-inositol (mostly in China and Japan) started with phytate (IP6) extracted from the soaking water resulting from corn and rice bran processing. After purification, the phytate is hydrolized, andmyo-inositol is separated by crystallization.[3]
Another route is microbial fermentation of carbohydrates by various organisms, such as the fungusNeurospora crassa (Beadle and Tatum, 1945),Candida boidini (Shirai et al., 1997),Saccharomyces cerevisiae (Culbertson et al., 1976),Escherichia coli (Hansen, 1999).[3] Alternatively, enzyme extracts from microbial cultures can be used in vitro to obtainmyo-inositol from various substrates, including glucose,sucrose,starch,xylose, andamylose.[3]
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