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DL-allo-Isoleucin
2-AMINO-3-METHYLPENTANOIC ACID · FEMA 3295 · H-DL-ILE-OH · (2RS,3RS)-2-Amino-3-methylpentanoic acid · DL-Isoleucine (mixture of 4 stereoisomers) · DL-Ile-OH · H-DL-lle-OH · DL-Isoleucin
Identifikatoren & physikalische Daten
| CAS No. | 443-79-8 |
|---|---|
| Summenformel | C6H13NO2 |
| Durchschnittliche Molmasse | 131,17 g/mol |
| Monoisotopische Masse | 131,09462866 g/mol |
| SMILES | CC[C@H](C)[C@H](N)C(=O)O |
| InChIKey | AGPKZVBTJJNPAG-WHFBIAKZSA-N |
| PubChem CID | 6306 |
| ChEMBL | CHEMBL1233584 |
| ChEBI | CHEBI:17191 |
| EC No. | 200-798-2 |
| DTXSID | DTXSID2046882 |
| Lokaler Name | DL-allo-Isoleucin |
Chemische & physikalische Eigenschaften
| XLogP | -1,7 |
|---|---|
| Polarare Oberfläche (TPSA) | 63,3 |
| H-Brücken-Donoren | 2 |
| H-Brücken-Akzeptoren | 3 |
| Frei drehbare Bindungen | 3 |
| Schwere Atome | 9 |
| Formalladung | 0 |
| Komplexität | 103 |
| Stoffklassen | Biological Agents -> Amino Acids and Derivatives |
| Lipide | Fatty Acyls [FA] -> Fatty Acids and Conjugates [FA01] -> Amino fatty acids [FA0110] |
| Kosmetika | Cosmetic ingredients (Isoleucine) -> CIR (Cosmetic Ingredient Review)Hair dyeingAntistaticSkin conditioning |
| LogP (Verteilungskoeffizient) | log Kow = -1.72-1.70 |
| Geschmack | Bitter |
| Lebensmittelzusatzstoffe | FLAVORING AGENT OR ADJUVANT, NUTRIENT SUPPLEMENT -> FDA Substance added to food |
| Color/Form | Waxy, shiny, rhombic leaflets from alcoholCrystals |
| Löslichkeit | Glistening rhombic or monoclinic plates from dilute alcohol. Decomposes at 292 °C. pK1 = 2.32pK2 = 9.76. Solubility in water (g/L): 18.3 at 0 °C22.3 at 25 °C30.3 at 50 °C46.1 at 75 °C78.0 at 100 °C /Isoleucine, DL-form/Sparingly soluble in hot alcohol (0.13% wt/wt at 80 °C), hot acetic acid. Insoluble in ether.Solubility in water (g/L): 37.9 at 0 °C41.2 at 25 °C48.2 at 50 °C60.8 at 75 °C82.6 at 100 °CIn water, 3.44X10+4 mg/L at 25 °C35 mg/mL22.3 g/L (25 ºC) |
| Dietary Ingredients | Isoleucine |
| Siedepunkt | Sublimes at 168-170 °C225.8±23.0 °C(Predicted) |
| Decomposition | When heated to decomposition, it emits toxic fumes of /nitric oxide/. |
| Schmelzpunkt | 284 °C (decomposes)285.5 °C290 °C (dec.) (lit.) |
| Dichte | 1.2930 (estimate) |
| Brechungsindex | 1.4630 (estimate) |
| FEMA | 3295 | D,L-ISOLEUCINE |
| Lagerbedingungen | Keep in dark place,Inert atmosphere,Room temperature |
| pKa (Säurekonstante) | pKa: 9.758(25°C) |
| Aggregatzustand | Powder |
| Farbe | White |
| Geruch | at 100.00 %. odorless |
| Geruchsart | odorless |
| Biologische Quelle | synthetic |
| Merck | 14,5179 |
| JECFA Number | 1422 |
| BRN | 1721796 |
| Stabilität | Stable. Incompatible with strong oxidizing agents. |
| Hauptanwendungen | flavors and fragrances |
| Kosmetik-Inhaltsstoffe Funktionen | SKIN CONDITIONINGANTISTATICHAIR CONDITIONING |
| InChI | 1S/C6H13NO2/c1-3-4(2)5(7)6(8)9/h4-5H,3,7H2,1-2H3,(H,8,9)/t4-,5-/m1/s1 |
| InChIKey | AGPKZVBTJJNPAG-UHFFFAOYSA-N |
| SMILES | CC[C@@H](C)[C@@H](N)C(O)=O |
| LogP (Verteilungskoeffizient) | 0.73 |
| CAS Datenbank | 443-79-8(CAS DataBase Reference) |
| NIST chemische Informationen | DL-Isoleucine(443-79-8) |
| EPA chemische Informationen | Isoleucine (443-79-8) |
Sicherheit & Vorschriften
| GHS-Einstufung | This chemical does not meet GHS hazard criteria for 98.8% (169 of 171) of all reports.Not ClassifiedAggregated GHS information provided per 171 reports by companies from 3 notifications to the ECHA C&L Inventory. |
|---|---|
| Regulatorische Informationen | Chemical: L-IsoleucineRegulation (EC) No 1831/2003 (amended)L-Isoleucine is listed on the EPA's Chemical Data Reporting (CDR) system. Manufacturers and importers of L-Isoleucine are required to report information about their production and use of this chemical to the EPA under the Toxic Substances Control Act (TSCA). (40 eCFR Part 711)Status: Active Update: 07-04-2022 https://echa.europa.eu/registration-dossier/-/registered-dossier/20720Isoleucine: Does not have an individual approval but may be used under an appropriate group standardL-Isoleucine: Does not have an individual approval but may be used under an appropriate group standard |
| Weitere Sicherheitsinformationen | IMAP assessments - L-Isoleucine: Environment tier I assessment |
| Gefahrenübersicht | May cause irritationShown to have tumor promoting activity for bladder carcinomas[Sigma-Aldrich MSDS] |
| FDA-Anforderungen | L-Isoleucine is a food additive permitted for direct addition to food for human consumption, as long as 1) the quantity of the substance added to food does not exceed the amount reasonably required to accomplish its intended physical, nutritive, or other technical effect in food, and 2) any substance intended for use in or on food is of appropriate food grade and is prepared and handled as a food ingredient.Drug products containing certain active ingredients offered over-the-counter (OTC) for certain uses. A number of active ingredients have been present in OTC drug products for various uses, as described below. However, based on evidence currently available, there are inadequate data to establish general recognition of the safety and effectiveness of these ingredients for the specified uses: isoleucine is included in weight control drug products.Isoleucine used as a nutrient and/or dietary supplement in animal drugs, feeds, and related products is generally recognized as safe when used in accordance with good manufacturing or feeding practice. |
| Special Reports | NAS, Food and Nutrition Board, Institute of MedicineDietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids (Macronutrients). National Academy Press, Washington, D.C. (2009). [Table#7488] |
| Hazard Classes and Categories | Not Classified |
| Entsorgungsverfahren | SRP: Criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.SRP: At the time of review, regulatory criteria for small quantity disposal are subject to significant revision, however, household quantities of waste pharmaceuticals may be managed as follows: Mix with wet cat litter or coffee grounds, double bag in plastic, discard in trash.SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator. |
| Wechselwirkungen | It has been well established that the branched chain amino acids (BCAA) compete with other large neutral amino acids (LNAA, particularly tryptophan and tyrosine) for membrane transport. Although the BCAA do not act as direct precursors for neurotransmitters, they can affect transport of certain LNAA across the blood-brain barrier, and thereby influence central nervous system concentrations of certain neurotransmitters.... High dietary levels of leucine suppressed the growth of rats fed a low protein diet, and the growth suppression could be prevented by supplementation with isoleucine and valine. |
| Expositionspfade | Absorbed from the small intestine by a sodium-dependent active-transport process |
| Toxizitätsübersicht | Safe in the present practices of use and concentration. Ingredient, concentration, and use information are available in documents discoverable at https://cir-reports.cir-safety.org(Applies to Valine, Leucine and Isoleucine) <br/>This group of essential amino acids are identified as the branched-chain amino acids, BCAAs. Because this arrangement of carbon atoms cannot be made by humans, these amino acids are an essential element in the diet. The catabolism of all three compounds initiates in muscle and yields NADH and FADH2 which can be utilized for ATP generation. The catabolism of all three of these amino acids uses the same enzymes in the first two steps. The first step in each case is a transamination using a single BCAA aminotransferase, with a-ketoglutarate as amine acceptor. As a result, three different a-keto acids are produced and are oxidized using a common branched-chain a-keto acid dehydrogenase, yielding the three different CoA derivatives. Subsequently the metabolic pathways diverge, producing many intermediates. <br/>The principal product from valine is propionylCoA, the glucogenic precursor of succinyl-CoA. Isoleucine catabolism terminates with production of acetylCoA and propionylCoAthus isoleucine is both glucogenic and ketogenic. Leucine gives rise to acetylCoA and acetoacetylCoA, and is thus classified as strictly ketogenic. <br/>There are a number of genetic diseases associated with faulty catabolism of the BCAAs. The most common defect is in the branched-chain a-keto acid dehydrogenase. Since there is only one dehydrogenase enzyme for all three amino acids, all three a-keto acids accumulate and are excreted in the urine. The disease is known as Maple syrup urine disease because of the characteristic odor of the urine in afflicted individuals. Mental retardation in these cases is extensive. Unfortunately, since these are essential amino acids, they cannot be heavily restricted in the dietultimately, the life of afflicted individuals is short and development is abnormal The main neurological problems are due to poor formation of myelin in the CNS. |
| Plant Concentrations | Plants with the highest amount of Isoleucine(1). [Table#7486] |
| Signs and Symptoms | Symptoms of hypoglycemia |
| Natural Pollution Sources | L-Isoleucine is an essential branched-chain aliphatic amino acid found in many proteins. It is an isomer of leucine. It is important in hemoglobin synthesis and regulation of blood sugar and energy levels(1). /L-Isoleucine/Isoleucine is one of the nine indispensable amino acids that cannot be synthesized to meet body needs in animals and therefore must be provided in the diet(1). It is isolated from beet-sugar mother liquors(2). |
| Human Toxicity Excerpts | /CASE REPORTS/ A 19-month-old boy with 2-methyl-3-hydroxybutyryl-CoA dehydrogenase (MHBD) deficiency, a defect of isoleucine degradation, had cognitive and motor development delay, spastic diplegia, dysmorphism, and occipital periventricular white matter lesions on MRI scan of the brain. The urinary accumulation of the isoleucine metabolites 2-methyl-3-hydroxybutyrate and tiglylglycine was only moderate under basal conditions. These abnormalities became more pronounced after a 100 mg/kg oral isoleucine challenge. Enzyme studies showed a markedly decreased activity of MHBD in fibroblasts and lymphocytes. Sequence analysis of the involved X-chromosome gene (HADH2), revealed the presence of 364C -->G mutation in the patient. His mother was heterozygous for the 364C-->G mutation, whereas the mutation was not found in the other members of the family (father, brother, and sister). This report indicates that an enzyme defect in the metabolism of branched-chain fatty acid oxidation and isoleucine may present features resembling sequelae of neonatal hypoxic-ischemic brain injury. All patients with MHBD deficiency identified so far are characterized by a neurologic phenotype rather than ketoacidotic attacks, unlike patients with the related isoleucine defect beta-ketothiolase deficiency./CASE REPORTS/ ... A further case of recently reported 2-methyl-3-hydroxybutyryl-CoA dehydrogenase (MHBD) deficiency, a disorder of isoleucine metabolism/ is reported/. The development of pronounced brain atrophy and symmetrical alterations of the basal ganglia were observed and the importance of specific enzymatic tests is emphasized, which should be performed if urinary metabolites suggest impaired catabolism of isoleucine./CASE REPORTS/ Three patients, from two Spanish families, with 2-methyl-3-hydroxybutyryl-CoA dehydrogenase (MHBD) deficiency, a recently described X-linked neurodegenerative inborn error of isoleucine metabolism /are reported/. Two of them are males with severe lactic acidosis suggestive of a mitochondrial encephalopathy, and the third is a female who was less severely affected, suggesting skewed X-inactivation. Molecular studies revealed a new missense mutation, 740A-->G, in one family and a previously described mutation, 388C-->T, in the other, causing the amino acid substitutions N247S and R130C, respectively. Both male patients died, one of them despite treatment with an isoleucine-restricted diet, but the disease has remained stable in the female patient after 1 year of treatment./CASE REPORTS/ ... A novel inborn error of metabolism /was/ identified in a child with an unusual neurodegenerative disease. The male patient was born at term and recovered well from a postnatal episode of metabolic decompensation and lactic acidosis. Psychomotor development in the first year of life was only moderately delayed. After 14 mo of age, there was progressive loss of mental and motor skillsat 2 years of age, he was severely retarded with marked restlessness, choreoathetoid movements, absence of directed hand movements, marked hypotonia and little reaction to external stimuli. Notable laboratory findings included marked elevations of urinary 2-methyl-3-hydroxybutyrate and tiglylglycine without elevation of 2-methylacetoacetate, mild elevations of lactate in CSF and blood, and a slightly abnormal acylcarnitine profile. These abnormalities became more apparent after isoleucine challenge. Enzyme studies showed absent activity of 2-methyl-3-hydroxybutyryl-CoA dehydrogenase (MHBD) in the mitochondrial oxidation of 2-methyl branched-chain fatty acids and isoleucine. Under dietary isoleucine restriction, neurologic symptoms stabilized over the next 7 months.For more Human Toxicity Excerpts (Complete) data for L-Isoleucine (6 total), please visit the HSDB record page. |
| Carcinogen Classification | No indication of carcinogenicity to humans (not listed by IARC). |
| Non-Human Toxicity Excerpts | /LABORATORY ANIMALS: Acute Exposure/ Isoleucine, a branched chain amino acid, plays an important role in the improvement of glucose metabolism as evidenced by the increase of insulin-independent glucose uptake in vitro. This study evaluated the effect of isoleucine on glucose uptake and oxidation in fasted rats and on gluconeogenesis in vivo and in vitro. Oral administration of isoleucine decreased the plasma glucose level by 20% and significantly increased muscle glucose uptake by 71% without significant elevation of the plasma insulin level compared with controls at 60 min after administration. Furthermore, expiratory excretion of 14CO2 from [U-14C]glucose in isoleucine-administered rats was increased by 19% compared with controls. Meanwhile, isoleucine decreased AMP levels in the liver but did not affect hepatic glycogen synthesis. Under insulin-free conditions, isoleucine significantly inhibited glucose production when alanine was used as a glucogenic substrate in isolated hepatocytes. This inhibition by isoleucine was also associated with a decline in mRNA levels for phosphoenolpyruvate carboxykinase and glucose-6-phosphatase (G6Pase) and a decreased activity of G6Pase in isolated hepatocytes. These findings suggest that a reduction of gluconeogenesis in liver, along with an increase of glucose uptake in the muscle, is also involved in the hypoglycemic effect of isoleucine. In conclusion, isoleucine administration stimulates both glucose uptake in the muscle and whole body glucose oxidation, in addition to depressing gluconeogenesis in the liver, thereby leading to the hypoglycemic effect in rats./LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ /In/ a subchronic feeding study L-isoleucine was administered to groups of 10 rats at dietary concentrations of 0, 1.25, 2.5, 5.0, or 8.0% for 13 weeks. The amino acid caused no changes in body weights, food consumption, or hematological parameters. At the highest dietary level, increased urine volumes and relative kidney weights and urine pH, together with some alterations in serum electrolytes, were clearly related to treatment. Minimal changes were observed at the 5.0% dietary level, although no histopathological alterations were observed in any organs of either gender. No alterations of any type were observed at the 2.5% dietary level (corresponding to about 1,800 mg/kg/day)./LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ There is evidence that isoleucine acts as a promoter of urinary bladder carcinogenesis in rats. Thus, ... 6-week-old rats /were exposed/ to low doses of N-butyl-N (4-hydroxybutyl) nitrosamine (BHBN), a known initiator of cancer of the urinary bladder, and ... their diets /were supplemented/ with isoleucine or leucine. After 40 weeks, the incidence of papillomas was significantly elevated in rats receiving isoleucine plus BHBN over that observed in the group receiving BHBN alone./LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ In a follow-up study of similar design, ... the experimental period /was extended/ to 60 weeks and included diets supplemented with 2 or 4% isoleucine or leucine. In this case, both dose levels of both amino acids significantly increased bladder carcinoma incidence over groups receiving BHBN alone or groups receiving amino acids alone (see table). It thus appears that both leucine and isoleucine are potent promoters of bladder neoplasms in rats at dietary levels of 2% and abovea no-effect level was not identified in either of the above studies. There is no evidence that either amino acid is carcinogenic in the absence of an initiating agent. (a) = Dietary level refers to level of amino acid addition. N-butyl-N (4-hydroxybutyl) nitrosamine (BHNB) was administered at a dose below that known to induce bladder tumors. No papillomas or preneoplastic lesions were observed in the control groups or in the amino acid groups.For more Non-Human Toxicity Excerpts (Complete) data for L-Isoleucine (9 total), please visit the HSDB record page. |
| Populations at Special Risk | 2-methyl-3-hydroxybutyryl-CoA dehydrogenase (MHBD) deficiency is a recently described X-linked neurodegenerative inborn error of isoleucine metabolism.Markedly elevated concentrations of branched chain amino acids (BCAA) and branched-chain alpha-keto acids are associated with maple-syrup urine diseasethe latter is caused by an inborn error of metabolism in which branched-chain ketoacid dehydrogenase (BCKAD) is low or absent. BCAA imbalances appear not to cause these various diseases and physiological abnormalities, but rather result from them. |
| Probable Routes of Human Exposure | NIOSH (NOES Survey 1981-1983) has statistically estimated that 18,202 workers (13,865 of these were female) were potentially exposed to isoleucine in the US(1). |
| Antidote and Emergency Treatment | /SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B//SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B//SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/ |
| Wassergefährdungsklasse (WGK) | 3 |
| TSCA-Inventar-Status | TSCA listed |
| Zollcode | 29224995 |
| R-Sätze (R) | 20/21/22-40 |
| Gefahrensymbole | Xn |
| Sicherheitshinweise (S) | 22-24/25-36 |
| Lagerklasse | 11 - Combustible Solids |
Anwendungen & Verwendung
Beschreibung
dl-Isoleucine is flavorless. It may be prepared from the corresponding aldehyde by Bucherer’s reaction.
Herstellung & Synthese
synthetische
From the corresponding aldehyde by Bucherer’s reaction.