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Identification
Name L-Isoleucine
Accession Number DB00167 (NUTR00031)
Type small molecule
Groups approved, 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
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
(2S,3S)-2-Amino-3-methylpentanoic acid
(2S,3S)-a-Amino-b-methyl-n-valeric acid
(2S,3S)-a-Amino-b-methylvaleric acid
(S,S)-Isoleucine
(S)-Isoleucine
2-Amino-3-methylvaleric acid
2S,3S-Isoleucine
erythro-L-Isoleucine
Isoleucine
L-(+)-Isoleucine
L-Ile
First Prev Next Last
Salts Not Available
Brand names Not Available
Brand mixtures Not Available
Categories
  • Dietary supplement
  • Micronutrient
  • Essential Amino Acids
CAS number 73-32-5
Weight Average: 131.1729
Monoisotopic: 131.094628665
Chemical Formula C6H13NO2
InChI Key InChIKey=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
Plain Text
IUPAC Name
(2S,3S)-2-amino-3-methylpentanoic acid
SMILES
CC[C@H](C)[C@H](N)C(O)=O
Plain Text
Mass Spec show (2.96 KB)
Taxonomy
Kingdom Organic
Classes
  • Amino Acids
Substructures
  • Amino Acids
  • Hydroxy Compounds
  • Acetates
  • Aliphatic and Aryl Amines
  • Carboxylic Acids and Derivatives
Pharmacology
Indication The branched-chain amino acids may have antihepatic encephalopathy activity in some. They may also have anticatabolic and antitardive dyskinesia activity.
Pharmacodynamics They 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.
Absorption Absorbed from the small intestine by a sodium-dependent active-transport process
Volume of distribution Not Available
Protein binding Not Available
Metabolism Hepatic
Route of elimination Not Available
Half life Not Available
Clearance Not Available
Toxicity Symptoms of hypoglycemia, increased mortality in ALS patients taking large doses of BCAAs
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers Not Available
Packagers
Dosage forms
Form Route Strength
Capsule Oral
Powder Oral
Tablet Oral
Prices
Unit description Cost Unit
L-isoleucine powder 3.21 USD g
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents Not Available
Properties
State solid
Experimental Properties
Property Value Source
melting point 285.5 dec °C PhysProp
water solubility 3.44E+004 mg/L (at 25 °C) YALKOWSKY,SH & DANNENFELSER,RM (1992)
logP -1.70 HANSCH,C ET AL. (1995)
pKa 2.37 (at 0 °C) KORTUM,G ET AL (1961)
Predicted Properties
Property Value Source
water solubility 1.14e+02 g/l ALOGPS
logP -1.7 ALOGPS
logP -1.5 ChemAxon
logS -0.06 ALOGPS
pKa (strongest acidic) 2.79 ChemAxon
pKa (strongest basic) 9.59 ChemAxon
physiological charge 0 ChemAxon
hydrogen acceptor count 3 ChemAxon
hydrogen donor count 2 ChemAxon
polar surface area 63.32 ChemAxon
rotatable bond count 3 ChemAxon
refractivity 34.09 ChemAxon
polarizability 14.11 ChemAxon
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Drug D00065 Link_out
KEGG Compound C00407 Link_out
PubChem Compound 6306 Link_out
PubChem Substance 46506864 Link_out
ChemSpider 6067 Link_out
ChEBI 17191 Link_out
ChEMBL 17191 Link_out
PharmGKB PA164750430 Link_out
IUPHAR 3311 Link_out
Guide to Pharmacology 3311 Link_out
HET ILE Link_out
PDRhealth http://www.pdrhealth.com/drug_info/nmdrugprofiles/nutsupdrugs/bra_0042.shtml Link_out
ATC Codes Not Available
AHFS Codes Not Available
PDB Entries
FDA label Not Available
MSDS show (72.8 KB)
Interactions
Drug Interactions Not Available
Food Interactions Not Available
Targets

1. Isoleucine-tRNA synthetase

Pharmacological action: unknown
Organism class: human
UniProt ID: Q5TCD1 Link_out
Gene: IARS Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Kedzierski W, Pawelkiewicz J: Interaction of lupin isoleucine-tRNA synthetase with isoleucine transfer ribonucleic acid measured by the thermal inactivation method. Acta Biochim Pol. 1971;18(2):153-61. Pubmed
  4. Schmidt E, Schimmel P: Mutational isolation of a sieve for editing in a transfer RNA synthetase. Science. 1994 Apr 8;264(5156):265-7. Pubmed
  5. Schimmel P, Landro JA, Schmidt E: Evidence for distinct locations for metal binding sites in two closely related class I tRNA synthetases. J Biomol Struct Dyn. 1993 Dec;11(3):571-81. Pubmed

2. Isoleucyl-tRNA synthetase, mitochondrial

Pharmacological action: unknown

ATP + L-isoleucine + tRNA(Ile) = AMP + diphosphate + L-isoleucyl-tRNA(Ile)

Organism class: human
UniProt ID: Q9NSE4 Link_out
Gene: IARS2 Link_out
Protein Sequence: FASTA
SNPs: SNPJam Report Link_out

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

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

Pharmacological action: unknown

Has greatest activity toward short branched chain acyl- CoA derivative such as (s)-2-methylbutyryl-CoA, isobutyryl-CoA, and 2-methylhexanoyl-CoA as well as toward short straight chain acyl-CoAs such as butyryl-CoA and hexanoyl-CoA. Can use valproyl- CoA as substrate and may play a role in controlling the metabolic flux of valproic acid in the development of toxicity of this agent

Organism class: human
UniProt ID: P45954 Link_out
Gene: ACADSB Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

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

Pharmacological action: unknown

Catalyzes the first reaction in the catabolism of the essential branched chain amino acids leucine, isoleucine, and valine

Organism class: human
UniProt ID: P54687 Link_out
Gene: BCAT1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

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

Pharmacological action: unknown

Catalyzes the first reaction in the catabolism of the essential branched chain amino acids leucine, isoleucine, and valine. May also function as a transporter of branched chain alpha-keto acids

Organism class: human
UniProt ID: O15382 Link_out
Gene: BCAT2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

6. Isoleucyl-tRNA synthetase, cytoplasmic

Pharmacological action: unknown
Organism class: human
UniProt ID: P41252 Link_out
Gene: IARS Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
Transporters

1. Monocarboxylate transporter 10

Actions: inhibitor

Sodium-independent transporter that mediates the update of aromatic acid. Can function as a net efflux pathway for aromatic amino acids in the basosolateral epithelial cells (By similarity)

UniProt ID: Q8TF71 Link_out
Gene: SLC16A10 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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 February 08, 2013 16:19