Welcome to DrugBank 4.0! If you prefer, you can still go back to version 3.0.
Identification
NameL-Isoleucine
Accession NumberDB00167  (NUTR00031)
Typesmall molecule
Groupsapproved, nutraceutical
Description

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. [PubChem]

Structure
Thumb
Synonyms
SynonymLanguageCode
(2S,3S)-2-Amino-3-methylpentanoic acidNot AvailableNot Available
2-Amino-3-methylvaleric acidNot AvailableNot Available
alpha-amino-beta-methylvaleric acidNot AvailableNot Available
IleNot AvailableNot Available
IsoleucineNot AvailableNot Available
α-amino-β-methylvaleric acidNot AvailableNot Available
SaltsNot Available
Brand namesNot Available
Brand mixturesNot Available
CategoriesNot Available
CAS number73-32-5
WeightAverage: 131.1729
Monoisotopic: 131.094628665
Chemical FormulaC6H13NO2
InChI KeyInChIKey=AGPKZVBTJJNPAG-WHFBIAKZSA-N
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
IUPAC Name
(2S,3S)-2-amino-3-methylpentanoic acid
SMILES
CC[C@H](C)[C@H](N)C(O)=O
Mass Specshow(2.96 KB)
Taxonomy
KingdomOrganic Compounds
SuperclassOrganic Acids and Derivatives
ClassCarboxylic Acids and Derivatives
SubclassAmino Acids, Peptides, and Analogues
Direct parentAlpha Amino Acids and Derivatives
Alternative parentsAmino Fatty Acids; Enolates; Polyamines; Carboxylic Acids; Monoalkylamines
Substituentscarboxylic acid; enolate; polyamine; primary amine; amine; primary aliphatic amine; organonitrogen compound
Classification descriptionThis compound belongs to the alpha amino acids and derivatives. These are amino acids in which the amino group is attached to the carbon atom immediately adjacent to the carboxylate group (alpha carbon), or a derivative thereof.
Pharmacology
IndicationThe branched-chain amino acids may have antihepatic encephalopathy activity in some. They may also have anticatabolic and antitardive dyskinesia activity.
PharmacodynamicsThey provide ingredients for the manufacturing of other essential biochemical components in the body, some of which are utilized for the production of energy, stimulants to the upper brain and helping you to be more alert.
Mechanism of action(Applies to Valine, Leucine and Isoleucine)
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.
The principal product from valine is propionylCoA, the glucogenic precursor of succinyl-CoA. Isoleucine catabolism terminates with production of acetylCoA and propionylCoA; thus isoleucine is both glucogenic and ketogenic. Leucine gives rise to acetylCoA and acetoacetylCoA, and is thus classified as strictly ketogenic.
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 diet; ultimately, 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.
AbsorptionAbsorbed from the small intestine by a sodium-dependent active-transport process
Volume of distributionNot Available
Protein bindingNot Available
Metabolism

Hepatic

Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicitySymptoms of hypoglycemia, increased mortality in ALS patients taking large doses of BCAAs
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategorySMPDB ID
2-Methyl-3-Hydroxybutryl CoA Dehydrogenase DeficiencyDiseaseSMP00137
3-Methylglutaconic Aciduria Type IVDiseaseSMP00141
3-Hydroxy-3-Methylglutaryl-CoA Lyase DeficiencyDiseaseSMP00138
3-Methylcrotonyl Coa Carboxylase Deficiency Type IDiseaseSMP00237
3-Methylglutaconic Aciduria Type IDiseaseSMP00139
3-Methylglutaconic Aciduria Type IIIDiseaseSMP00140
3-hydroxyisobutyric acid dehydrogenase deficiencyDiseaseSMP00521
3-hydroxyisobutyric aciduriaDiseaseSMP00522
Lactic AcidemiaDiseaseSMP00313
Propionic AcidemiaDiseaseSMP00236
Isovaleric acidemiaDiseaseSMP00524
Isovaleric AciduriaDiseaseSMP00238
Methylmalonic AciduriaDiseaseSMP00200
Alanine MetabolismMetabolicSMP00055
Beta-Ketothiolase DeficiencyDiseaseSMP00173
Pyruvate Carboxylase DeficiencyDiseaseSMP00350
Isobutyryl-coa dehydrogenase deficiencyDiseaseSMP00523
Methylmalonate Semialdehyde Dehydrogenase DeficiencyDiseaseSMP00384
Valine, Leucine and Isoleucine DegradationMetabolicSMP00032
Maple Syrup Urine DiseaseDiseaseSMP00199
Primary Hyperoxaluria Type IDiseaseSMP00352
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.9677
Blood Brain Barrier + 0.78
Caco-2 permeable - 0.7966
P-glycoprotein substrate Non-substrate 0.7385
P-glycoprotein inhibitor I Non-inhibitor 0.9825
P-glycoprotein inhibitor II Non-inhibitor 0.9739
Renal organic cation transporter Non-inhibitor 0.9696
CYP450 2C9 substrate Non-substrate 0.8513
CYP450 2D6 substrate Non-substrate 0.8372
CYP450 3A4 substrate Non-substrate 0.7827
CYP450 1A2 substrate Non-inhibitor 0.8536
CYP450 2C9 substrate Non-inhibitor 0.8762
CYP450 2D6 substrate Non-inhibitor 0.9
CYP450 2C19 substrate Non-inhibitor 0.9386
CYP450 3A4 substrate Non-inhibitor 0.9155
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.97
Ames test Non AMES toxic 0.903
Carcinogenicity Non-carcinogens 0.632
Biodegradation Ready biodegradable 0.5166
Rat acute toxicity 1.5846 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9921
hERG inhibition (predictor II) Non-inhibitor 0.9735
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage forms
FormRouteStrength
CapsuleOral
PowderOral
TabletOral
Prices
Unit descriptionCostUnit
L-isoleucine powder3.21USDg
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point285.5 dec °CPhysProp
water solubility3.44E+004 mg/L (at 25 °C)YALKOWSKY,SH & DANNENFELSER,RM (1992)
logP-1.70HANSCH,C ET AL. (1995)
pKa2.37 (at 0 °C)KORTUM,G ET AL (1961)
Predicted Properties
PropertyValueSource
water solubility1.14e+02 g/lALOGPS
logP-1.7ALOGPS
logP-1.5ChemAxon
logS-0.06ALOGPS
pKa (strongest acidic)2.79ChemAxon
pKa (strongest basic)9.59ChemAxon
physiological charge0ChemAxon
hydrogen acceptor count3ChemAxon
hydrogen donor count2ChemAxon
polar surface area63.32ChemAxon
rotatable bond count3ChemAxon
refractivity34.09ChemAxon
polarizability14.11ChemAxon
number of rings0ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterNoChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleNoChemAxon
Spectra
Spectra
References
Synthesis Reference

Nelli I. Zhdanova, Tatyana V. Leonova, Ljudmila F. Kozyreva, “Method of producing L-isoleucine using Brevibacterium flavum.” U.S. Patent US4237228, issued February, 1962.

US4237228
General ReferenceNot Available
External Links
ResourceLink
KEGG DrugD00065
KEGG CompoundC00407
PubChem Compound6306
PubChem Substance46506864
ChemSpider6067
ChEBI17191
ChEMBLCHEMBL1233584
PharmGKBPA164750430
IUPHAR3311
Guide to Pharmacology3311
HETILE
PDRhealthhttp://www.pdrhealth.com/drug_info/nmdrugprofiles/nutsupdrugs/bra_0042.shtml
ATC CodesNot Available
AHFS CodesNot Available
PDB Entries
FDA labelNot Available
MSDSshow(72.8 KB)
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

1. Isoleucine--tRNA ligase, mitochondrial

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Isoleucine--tRNA ligase, mitochondrial Q9NSE4 Details

References:

  1. Wang P, Tang Y, Tirrell DA: Incorporation of trifluoroisoleucine into proteins in vivo. J Am Chem Soc. 2003 Jun 11;125(23):6900-6. Pubmed
  2. Fukunaga R, Fukai S, Ishitani R, Nureki O, Yokoyama S: Crystal structures of the CP1 domain from Thermus thermophilus isoleucyl-tRNA synthetase and its complex with L-valine. J Biol Chem. 2004 Feb 27;279(9):8396-402. Epub 2003 Dec 12. Pubmed
  3. Zhu B, Zhao MW, Eriani G, Wang ED: A present-day aminoacyl-tRNA synthetase with ancestral editing properties. RNA. 2007 Jan;13(1):15-21. Epub 2006 Nov 9. Pubmed
  4. Fukunaga R, Yokoyama S: Crystal structure of leucyl-tRNA synthetase from the archaeon Pyrococcus horikoshii reveals a novel editing domain orientation. J Mol Biol. 2005 Feb 11;346(1):57-71. Epub 2004 Dec 19. Pubmed
  5. Fukunaga R, Yokoyama S: Structural basis for substrate recognition by the editing domain of isoleucyl-tRNA synthetase. J Mol Biol. 2006 Jun 16;359(4):901-12. Epub 2006 Apr 25. Pubmed

2. Short/branched chain specific acyl-CoA dehydrogenase, mitochondrial

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Short/branched chain specific acyl-CoA dehydrogenase, mitochondrial P45954 Details

References:

  1. Korman SH, Andresen BS, Zeharia A, Gutman A, Boneh A, Pitt JJ: 2-ethylhydracrylic aciduria in short/branched-chain acyl-CoA dehydrogenase deficiency: application to diagnosis and implications for the R-pathway of isoleucine oxidation. Clin Chem. 2005 Mar;51(3):610-7. Epub 2004 Dec 22. Pubmed
  2. Madsen PP, Kibaek M, Roca X, Sachidanandam R, Krainer AR, Christensen E, Steiner RD, Gibson KM, Corydon TJ, Knudsen I, Wanders RJ, Ruiter JP, Gregersen N, Andresen BS: Short/branched-chain acyl-CoA dehydrogenase deficiency due to an IVS3+3A>G mutation that causes exon skipping. Hum Genet. 2006 Feb;118(6):680-90. Epub 2005 Nov 30. Pubmed
  3. Korman SH: Inborn errors of isoleucine degradation: a review. Mol Genet Metab. 2006 Dec;89(4):289-99. Epub 2006 Sep 6. Pubmed

3. Branched-chain-amino-acid aminotransferase, cytosolic

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Branched-chain-amino-acid aminotransferase, cytosolic P54687 Details

References:

  1. Goto M, Miyahara I, Hayashi H, Kagamiyama H, Hirotsu K: Crystal structures of branched-chain amino acid aminotransferase complexed with glutamate and glutarate: true reaction intermediate and double substrate recognition of the enzyme. Biochemistry. 2003 Apr 8;42(13):3725-33. Pubmed
  2. Chen CD, Huang TF, Lin CH, Guan HH, Hsieh YC, Lin YH, Huang YC, Liu MY, Chang WC, Chen CJ: Purification, crystallization and preliminary X-ray crystallographic analysis of branched-chain aminotransferase from Deinococcus radiodurans. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2007 Jun 1;63(Pt 6):492-4. Epub 2007 May 5. Pubmed
  3. Beck HC: Branched-chain fatty acid biosynthesis in a branched-chain amino acid aminotransferase mutant of Staphylococcus carnosus. FEMS Microbiol Lett. 2005 Feb 1;243(1):37-44. Pubmed
  4. Thage BV, Rattray FP, Laustsen MW, Ardo Y, Barkholt V, Houlberg U: Purification and characterization of a branched-chain amino acid aminotransferase from Lactobacillus paracasei subsp. paracasei CHCC 2115. J Appl Microbiol. 2004;96(3):593-602. Pubmed
  5. Madsen SM, Beck HC, Ravn P, Vrang A, Hansen AM, Israelsen H: Cloning and inactivation of a branched-chain-amino-acid aminotransferase gene from Staphylococcus carnosus and characterization of the enzyme. Appl Environ Microbiol. 2002 Aug;68(8):4007-14. Pubmed

4. Branched-chain-amino-acid aminotransferase, mitochondrial

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Branched-chain-amino-acid aminotransferase, mitochondrial O15382 Details

References:

  1. Berger BJ, English S, Chan G, Knodel MH: Methionine regeneration and aminotransferases in Bacillus subtilis, Bacillus cereus, and Bacillus anthracis. J Bacteriol. 2003 Apr;185(8):2418-31. Pubmed

5. Isoleucine--tRNA ligase, cytoplasmic

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Isoleucine--tRNA ligase, cytoplasmic P41252 Details

References:

  1. Crasto CF, Forrest AK, Karoli T, March DR, Mensah L, O’Hanlon PJ, Nairn MR, Oldham MD, Yue W, Banwell MG, Easton CJ: Synthesis and activity of analogues of the isoleucyl tRNA synthetase inhibitor SB-203207. Bioorg Med Chem. 2003 Jul 3;11(13):2687-94. Pubmed
  2. Wang P, Tang Y, Tirrell DA: Incorporation of trifluoroisoleucine into proteins in vivo. J Am Chem Soc. 2003 Jun 11;125(23):6900-6. Pubmed
  3. Mock ML, Michon T, van Hest JC, Tirrell DA: Stereoselective incorporation of an unsaturated isoleucine analogue into a protein expressed in E. coli. Chembiochem. 2006 Jan;7(1):83-7. Pubmed
  4. Fukunaga R, Fukai S, Ishitani R, Nureki O, Yokoyama S: Crystal structures of the CP1 domain from Thermus thermophilus isoleucyl-tRNA synthetase and its complex with L-valine. J Biol Chem. 2004 Feb 27;279(9):8396-402. Epub 2003 Dec 12. Pubmed
  5. Pezo V, Metzgar D, Hendrickson TL, Waas WF, Hazebrouck S, Doring V, Marliere P, Schimmel P, De Crecy-Lagard V: Artificially ambiguous genetic code confers growth yield advantage. Proc Natl Acad Sci U S A. 2004 Jun 8;101(23):8593-7. Epub 2004 May 26. Pubmed

1. Monocarboxylate transporter 10

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Monocarboxylate transporter 10 Q8TF71 Details

References:

  1. Kim DK, Kanai Y, Chairoungdua A, Matsuo H, Cha SH, Endou H: Expression cloning of a Na+-independent aromatic amino acid transporter with structural similarity to H+/monocarboxylate transporters. J Biol Chem. 2001 May 18;276(20):17221-8. Epub 2001 Feb 20. Pubmed

Comments
Drug created on June 13, 2005 07:24 / Updated on September 24, 2013 14:04