1.0 2020-03-18 23:25:58 UTC 2022-12-13 23:36:23 UTC CDB000132 L-Isoleucine L-isoleucine or isoleucine, abbreviated as Ile or I, is one of the essential amino acids used in the biosynthesis of proteins. It contains an Œ±-amino group (which is in the protonated ‚àíNH3+ form under biological conditions), an Œ±-carboxylic acid group (which is in the deprotonated ‚àíCOO‚àí form under biological conditions), and a hydrocarbon side chain with a branch (a central carbon atom bound to three other carbon atoms). It is classified as a non-polar, uncharged (at physiological pH), branched-chain, aliphatic amino acid. In plants and microorganisms, it is synthesized via several steps, starting from pyruvate and alpha-ketobutyrate. Isoleucine is one of the three branched chain amino acids (BCAA), together with leucine and valine. Branched chain amino acids (BCAA) are essential amino acids whose carbon structure is marked by a branch point. Isoleucine is less concentrated in foods compared to leucine and valine. A cup of milk contains 800 mg of leucine and only 500 mg of isoleucine and valine. A cup of wheat germ has about 1.6 g of leucine and 1 g of isoleucine and valine. Eggs and cheese have about equal amounts of the BCAA and contain about 400 mg of leucine and 400 mg of valine and isoleucine. Pork contains 7 to 8 g of leucine and 3 to 4 g of isoleucine and valine. L-isoleucine is also found in Cannabis plants (PMID: 6991645). These BCAA are critical to human life and are particularly involved in stress, energy and muscle metabolism. BCAA supplementation as therapy, both oral and intravenous, in human health and disease holds great promise. Despite their structural similarities, the branched amino acids have different metabolic routes, with valine going solely to carbohydrates, leucine solely to fats and isoleucine to both. The different metabolism accounts for different requirements for these essential amino acids in humans: 12 mg/kg, 14 mg/kg and 16 mg/kg of valine, leucine, and isoleucine, respectively. Furthermore, these amino acids have different deficiency symptoms. Valine deficiency is marked by neurological defects in the brain, while isoleucine deficiency is marked by muscle tremors. BCAA are decreased in patients with liver disease, such as hepatitis, hepatic coma, cirrhosis, extrahepatic biliary atresia or portacaval shunt; aromatic amino acids (AAA)-tyrosine, tryptophan and phenylalanine, as well as methionine-are increased in these conditions. Valine has been established as a useful supplemental therapy to the ailing liver. All the BCAA probably compete with AAA for absorption into the brain. Supplemental BCAA with vitamin B6 and zinc help normalize the BCAA:AAA ratio. The BCAA are not without side effects. Leucine alone, for example, exacerbates pellagra and can cause psychosis in pellagra patients by increasing excretion of niacin in the urine. Leucine may lower brain serotonin and dopamine whereas isoleucine may have potential as an antipsychotic treatment. A dose of 3 g of isoleucine added to the niacin regime cleared leucine-aggravated psychosis in schizophrenic patients. Moreover, L-isoleucine is associated with maple syrup urine disease (MSUD; PMID: 10234605), which is an inborn error of metabolism, so named for the sweet, maple syrup smell of urine. MSUD is an autosomal recessive disorder that affects the metabolism of the BCAA. Mutations occur in the 4 genes that comprise the branched-chain alpha-keto acid dehydrogenase complex, which breaks down the BCAA. (2S,3S)-2-Amino-3-methylpentanoic acid 2-Amino-3-methylvaleric acid alpha-Amino-beta-methylvaleric acid I Ile ISOLEUCINE (2S,3S)-2-Amino-3-methylpentanoate 2-Amino-3-methylvalerate a-Amino-b-methylvalerate a-Amino-b-methylvaleric acid alpha-Amino-beta-methylvalerate Α-amino-β-methylvalerate Α-amino-β-methylvaleric acid (2S,3S)-2-Amino-3-methyl-pentanoate (2S,3S)-2-Amino-3-methyl-pentanoic acid (2S,3S)-a-Amino-b-methyl-N-valerate (2S,3S)-a-Amino-b-methyl-N-valeric acid (2S,3S)-a-Amino-b-methylvalerate (2S,3S)-a-Amino-b-methylvaleric acid (2S,3S)-Alph-amino-beta-methylvalerate (2S,3S)-Alph-amino-beta-methylvaleric acid (2S,3S)-alpha-Amino-beta-merthyl-N-valerate (2S,3S)-alpha-Amino-beta-merthyl-N-valeric acid (2S,3S)-alpha-Amino-beta-merthylvalerate (2S,3S)-alpha-Amino-beta-merthylvaleric acid (2S,3S)-alpha-Amino-beta-methyl-N-valerate (2S,3S)-alpha-Amino-beta-methyl-N-valeric acid (2S,3S)-alpha-Amino-beta-methylvalerate (2S,3S)-alpha-Amino-beta-methylvaleric acid (S)-Isoleucine (S,S)-Isoleucine 2-Amino-3-methylpentanoate 2-Amino-3-methylpentanoic acid 2S,3S-Isoleucine Erythro-L-isoleucine Iso-leucine L-(+)-Isoleucine L-Ile [S-(R*,r*)]-2-amino-3-methylpentanoate [S-(R*,r*)]-2-amino-3-methylpentanoic acid Isoleucine, L-isomer Alloisoleucine Isoleucine, L isomer L-Isomer isoleucine 2S-Amino-3S-methylpentanoate L-Isoleucine C6H13NO2 131.17 131.0946 (2S,3S)-2-amino-3-methylpentanoic acid L-isoleucine 73-32-5 CC[C@H](C)[C@H](N)C(O)=O InChI=1S/C6H13NO2/c1-3-4(2)5(7)6(8)9/h4-5H,3,7H2,1-2H3,(H,8,9)/t4-,5-/m0/s1 AGPKZVBTJJNPAG-WHFBIAKZSA-N belongs to the class of organic compounds known as isoleucine and derivatives. Isoleucine and derivatives are compounds containing isoleucine or a derivative thereof resulting from reaction of isoleucine at the amino group or the carboxy group, or from the replacement of any hydrogen of glycine by a heteroatom. Isoleucine and derivatives Organic compounds Organic acids and derivatives Carboxylic acids and derivatives Amino acids, peptides, and analogues Aliphatic acyclic compounds Amino acids Carbonyl compounds Carboxylic acids Hydrocarbon derivatives L-alpha-amino acids Methyl-branched fatty acids Monoalkylamines Monocarboxylic acids and derivatives Organic oxides Organopnictogen compounds Aliphatic acyclic compound Alpha-amino acid Amine Amino acid Branched fatty acid Carbonyl group Carboxylic acid Fatty acid Fatty acyl Hydrocarbon derivative Isoleucine or derivatives L-alpha-amino acid Methyl-branched fatty acid Monocarboxylic acid or derivatives Organic nitrogen compound Organic oxide Organic oxygen compound Organonitrogen compound Organooxygen compound Organopnictogen compound Primary aliphatic amine Primary amine Amino fatty acids Common amino acids L-alpha-amino acid aspartate family amino acid isoleucine proteinogenic amino acid water_solubility 35 mg/mL Human Metabolome Project logp -1.70 HANSCH,C ET AL. (1995) melting_point 285.5 °C logp -1.73 ALOGPS logs -0.06 ALOGPS logp -1.5 ChemAxon pka_strongest_acidic 2.79 ChemAxon pka_strongest_basic 9.59 ChemAxon iupac (2S,3S)-2-amino-3-methylpentanoic acid ChemAxon average_mass 131.17 ChemAxon mono_mass 131.0946 ChemAxon smiles CC[C@H](C)[C@H](N)C(O)=O ChemAxon formula C6H13NO2 ChemAxon inchi InChI=1S/C6H13NO2/c1-3-4(2)5(7)6(8)9/h4-5H,3,7H2,1-2H3,(H,8,9)/t4-,5-/m0/s1 ChemAxon inchikey AGPKZVBTJJNPAG-WHFBIAKZSA-N ChemAxon polar_surface_area 63.32 ChemAxon refractivity 34.09 ChemAxon polarizability 14.11 ChemAxon rotatable_bond_count 3 ChemAxon acceptor_count 3 ChemAxon donor_count 2 ChemAxon physiological_charge 0 ChemAxon formal_charge 0 ChemAxon number_of_rings 0 ChemAxon bioavailability 1 ChemAxon rule_of_five Yes ChemAxon ghose_filter Yes ChemAxon veber_rule Yes ChemAxon mddr_like_rule Yes ChemAxon C00407 DB00167 FDB012397 6067 6306 17191 C00001374 ILE 34887 Isoleucine 5193 Turner CE, Elsohly MA, Boeren EG: Constituents of Cannabis sativa L. XVII. A review of the natural constituents. J Nat Prod. 1980 Mar-Apr;43(2):169-234. doi: 10.1021/np50008a001. 6991645 Podebrad F, Heil M, Reichert S, Mosandl A, Sewell AC, Bohles H: 4,5-dimethyl-3-hydroxy-2[5H]-furanone (sotolone)--the odour of maple syrup urine disease. J Inherit Metab Dis. 1999 Apr;22(2):107-14. doi: 10.1023/a:1005433516026. 10234605