Record Information
Version3.6
Creation Date2005-11-16 15:48:42 UTC
Update Date2013-02-09 00:09:06 UTC
HMDB IDHMDB00687
Secondary Accession NumbersNone
Metabolite Identification
Common NameL-Leucine
DescriptionBranched chain amino acids (BCAA) are essential amino acids whose carbon structure is marked by a branch point. These three amino acids 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. 'BCAA' denotes valine, isoleucine and leucine which are branched chain essential amino acids. 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. Many types of inborn errors of BCAA metabolism exist, and are marked by various abnormalities. The most common form is the maple syrup urine disease, marked by a characteristic urinary odor. Other abnormalities are associated with a wide range of symptoms, such as mental retardation, ataxia, hypoglycemia, spinal muscle atrophy, rash, vomiting and excessive muscle movement. Most forms of BCAA metabolism errors are corrected by dietary restriction of BCAA and at least one form is correctable by supplementation with 10 mg of biotin daily. BCAA are useful because they are metabolized primarily by muscle. Stress state- e.g surgery, trauma, cirrhosis, infections, fever and starvation--require proportionately more BCAA than other amino acids and probably proportionately more leucine than either valine or isoleucine. BCAA and other amino acids are frequently fed intravenously (TPN) to malnourished surgical patients and in some cases of severe trauma. BCAA, particularly leucine, stimulate protein synthesis, increase reutilization of amino acids in many organs and reduce protein breakdown. Furthermore, leucine can be an important source of calories, and is superior as fuel to the ubiquitous intravenous glucose (dextrose). Leucine also stimulates insulin release, which in turn stimulates protein synthesis and inhibits protein breakdown. These effects are particularly useful in athletic training. BCAA should also replace the use of steroids as commonly used by weightlifters. Huntington's chorea and anorexic disorders both are characterized by low serum BCAA. These diseases, as well as forms of Parkinson's, may respond to BCAA therapy. BCAA, and particularly leucine, are among the amino acids most essential for muscle health. (http://www.dcnutrition.com).
Structure
Thumb
Synonyms
  1. (2S)-2-Amino-4-methylpentanoate
  2. (2S)-2-Amino-4-methylpentanoic acid
  3. (S)-(+)-Leucine
  4. (S)-2-Amino-4-methylpentanoate
  5. (S)-2-Amino-4-methylpentanoic acid
  6. (S)-2-Amino-4-methylvalerate
  7. (S)-2-Amino-4-methylvaleric acid
  8. (S)-Leucine
  9. 4-Methyl-L-Norvaline
  10. L-(+)-Leucine
  11. L-a-Aminoisocaproate
  12. L-a-Aminoisocaproic acid
  13. L-alpha-Aminoisocaproate
  14. L-alpha-Aminoisocaproic acid
  15. Leu
  16. Leucine
Chemical FormulaC6H13NO2
Average Molecular Weight131.1729
Monoisotopic Molecular Weight131.094628665
IUPAC Name(2S)-2-amino-4-methylpentanoic acid
Traditional IUPAC NameD-leucine
CAS Registry Number61-90-5
SMILES
CC(C)C[C@H](N)C(O)=O
InChI Identifier
InChI=1S/C6H13NO2/c1-4(2)3-5(7)6(8)9/h4-5H,3,7H2,1-2H3,(H,8,9)/t5-/m0/s1
InChI KeyROHFNLRQFUQHCH-YFKPBYRVSA-N
Chemical Taxonomy
KingdomOrganic Compounds
Super ClassAmino Acids, Peptides, and Analogues
ClassAmino Acids and Derivatives
Sub ClassAlpha Amino Acids and Derivatives
Other Descriptors
  • Aliphatic Acyclic Compounds
  • Amino fatty acids(Lipidmaps)
  • a D-amino acid(Cyc)
  • alpha-amino acid(ChEBI)
  • branched-chain amino acid(ChEBI)
Substituents
  • Carboxylic Acid
  • Primary Aliphatic Amine (Alkylamine)
Direct ParentAlpha Amino Acids and Derivatives
Ontology
StatusDetected and Quantified
Origin
  • Drug
  • Food
Biofunction
  • Essential amino acids
  • Protein component
ApplicationNot Available
Cellular locations
  • Extracellular
  • Mitochondria
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point268 - 288 °CNot Available
Boiling PointNot AvailableNot Available
Water Solubility21.5 mg/mLNot Available
LogP-1.52HANSCH,C ET AL. (1995)
Predicted Properties
PropertyValueSource
water solubility69.8 g/LALOGPS
logP-1.8ALOGPS
logP-1.6ChemAxon
logS-0.27ALOGPS
pKa (strongest acidic)2.79ChemAxon
pKa (strongest basic)9.52ChemAxon
physiological charge0ChemAxon
hydrogen acceptor count3ChemAxon
hydrogen donor count2ChemAxon
polar surface area63.32ChemAxon
rotatable bond count3ChemAxon
refractivity34.17ChemAxon
polarizability14.25ChemAxon
Spectra
Spectra
Biological Properties
Cellular Locations
  • Extracellular
  • Mitochondria
Biofluid Locations
  • Blood
  • Cerebrospinal Fluid (CSF)
  • Urine
Tissue Location
  • Adipose Tissue
  • Adrenal Medulla
  • Bladder
  • Epidermis
  • Fibroblasts
  • Intestine
  • Kidney
  • Muscle
  • Nerve Cells
  • Neuron
  • Placenta
  • Platelet
  • Prostate
  • Skeletal Muscle
  • Testes
Pathways
NameSMPDB LinkKEGG Link
Transcription/TranslationSMP00019Not Available
Valine, Leucine and Isoleucine DegradationSMP00032map00280
Normal Concentrations
BiofluidStatusValueAgeSexConditionReference
BloodDetected and Quantified70.0 +/- 25.0 uMNewborn (0-30 days old)Not SpecifiedNormal
  • Geigy Scient...
BloodDetected and Quantified134.0 +/- 20.0 uMChildren (1-13 year old)MaleNormal
  • Geigy Scient...
BloodDetected and Quantified160.0 +/- 27.0 uMAdult (>18 years old)FemaleNormal
  • Geigy Scient...
BloodDetected and Quantified157.0 +/- 30.0 uMAdult (>18 years old)MaleNormal
  • Geigy Scient...
BloodDetected and Quantified123 (98-148) uMAdult (>18 years old)BothNormal
BloodDetected and Quantified251 +/- 5 uMAdult (>18 years old)BothNormal
BloodDetected and Quantified98.7 +/- 11.5 uMAdult (>18 years old)Not SpecifiedNormal
Cerebrospinal Fluid (CSF)Detected and Quantified16 +/- 9 uMNot SpecifiedBothNormal
Cerebrospinal Fluid (CSF)Detected and Quantified10.1 +/- 2.1 uMAdult (>18 years old)BothNormal
  • Geigy Scient...
Cerebrospinal Fluid (CSF)Detected and Quantified14.5 +/- 3.7 uMAdult (>18 years old)Not SpecifiedNormal
Cerebrospinal Fluid (CSF)Detected and Quantified18.6 +/- 4.1 uMAdult (>18 years old)Not SpecifiedNormal
Cerebrospinal Fluid (CSF)Detected and Quantified11.2 +/- 3.5 uMAdult (>18 years old)Not SpecifiedNormal
UrineDetected and Quantified3.5 umol/mmol creatinineAdult (>18 years old)BothNormal
UrineDetected and Quantified6.10-19.07 umol/mmol creatinineAdult (>18 years old)BothNormal
  • David F. Put...
UrineDetected and Quantified7.58 +/- 4.10 umol/mmol creatinineInfant (0-1 year old)BothNormal
UrineDetected and Quantified4.868 (1.842-8.421) umol/mmol creatinineAdult (>18 years old)BothNormal
    UrineDetected but not QuantifiedNot ApplicableAdult (>18 years old)BothCommentNormal
    UrineDetected and Quantified0.1 (0.0-0.2) umol/mmol creatinineNewborn (0-30 days old)BothNormal
    • Geigy Scient...
    • West Cadwell...
    • Basel, Switz...
    UrineDetected and Quantified2.5 +/- 1.0 umol/mmol creatinineChildren (1-13 year old)MaleNormal
    • Geigy Scient...
    • West Cadwell...
    • Basel, Switz...
    UrineDetected and Quantified3.0+/- 1.5 umol/mmol creatinineAdult (>18 years old)MaleNormal
    • Geigy Scient...
    • West Cadwell...
    • Basel, Switz...
    UrineDetected and Quantified2.5 +/- 1.3 umol/mmol creatinineAdult (>18 years old)FemaleNormal
    • Geigy Scient...
    • West Cadwell...
    • Basel, Switz...
    UrineDetected and Quantified3.0 (1.6-6.0) umol/mmol creatinineAdult (>18 years old)BothCommentNormal
    UrineDetected and Quantified2.8 (1.6-5.4) umol/mmol creatinineAdult (>18 years old)BothCommentNormal
    UrineDetected and Quantified1.2 umol/mmol creatinineAdult (>18 years old)BothNormal
    Abnormal Concentrations
    BiofluidStatusValueAgeSexConditionReference
    BloodDetected and Quantified74.8 +/- 34.3 uMAdult (>18 years old)Not SpecifiedHeart Transplant
    BloodDetected and Quantified66.0 +/- 161.0 uMNewborn (0-30 days old)BothPhenylketonuria (PKU)
    BloodDetected and Quantified95.3 (89.3-100.0) uMAdult (>18 years old)BothCommentEpilepsy
    BloodDetected and Quantified273.0 +/- 10.0 uMAdult (>18 years old)BothCommentHeart failure
    BloodDetected and Quantified103.0 (97.8-108.0) uMAdult (>18 years old)BothCommentEpilepsy
    BloodDetected and Quantified643.0 +/- 667.0 uMNewborn (0-30 days old)BothMaple syrup urine disease (MSUD)
    Cerebrospinal Fluid (CSF)Detected and Quantified11.5 +/- 1.5 uMAdult (>18 years old)BothAlzheimer's disease
    Cerebrospinal Fluid (CSF)Detected and Quantified16.5 +/- 7.0 uMChildren (1-13 year old)Not SpecifiedCommentLeukemia
    Cerebrospinal Fluid (CSF)Detected and Quantified13.1 +/- 5.6 uMChildren (1-13 year old)Not SpecifiedLeukemia
    UrineDetected and Quantified0.91 +/- 0.11 umol/mmol creatinineAdult (>18 years old)BothAlzheimer's disease
    Associated Disorders and Diseases
    Disease References
    Alzheimer's disease
    • Fonteh AN, Harrington RJ, Tsai A, Liao P, Harrington MG: Free amino acid and dipeptide changes in the body fluids from Alzheimer's disease subjects. Amino Acids. 2007 Feb;32(2):213-24. Epub 2006 Oct 10. Pubmed: 17031479
    Epilepsy
    • Rainesalo S, Keranen T, Palmio J, Peltola J, Oja SS, Saransaari P: Plasma and cerebrospinal fluid amino acids in epileptic patients. Neurochem Res. 2004 Jan;29(1):319-24. Pubmed: 14992292
    Heart failure
    • Norrelund H, Wiggers H, Halbirk M, Frystyk J, Flyvbjerg A, Botker HE, Schmitz O, Jorgensen JO, Christiansen JS, Moller N: Abnormalities of whole body protein turnover, muscle metabolism and levels of metabolic hormones in patients with chronic heart failure. J Intern Med. 2006 Jul;260(1):11-21. Pubmed: 16789974
    Leukemia
    • Peng CT, Wu KH, Lan SJ, Tsai JJ, Tsai FJ, Tsai CH: Amino acid concentrations in cerebrospinal fluid in children with acute lymphoblastic leukemia undergoing chemotherapy. Eur J Cancer. 2005 May;41(8):1158-63. Epub 2005 Apr 14. Pubmed: 15911239
    Maple syrup urine disease
    • Deng C, Shang C, Hu Y, Zhang X: Rapid diagnosis of phenylketonuria and other aminoacidemias by quantitative analysis of amino acids in neonatal blood spots by gas chromatography-mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2002 Jul 25;775(1):115-20. Pubmed: 12101068
    Phenylketonuria
    • Deng C, Shang C, Hu Y, Zhang X: Rapid diagnosis of phenylketonuria and other aminoacidemias by quantitative analysis of amino acids in neonatal blood spots by gas chromatography-mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2002 Jul 25;775(1):115-20. Pubmed: 12101068
    Associated OMIM IDs
    DrugBank IDNot Available
    DrugBank Metabolite IDNot Available
    Phenol Explorer Compound IDNot Available
    Phenol Explorer Metabolite IDNot Available
    FoodDB IDFDB001946
    KNApSAcK IDC00001377
    Chemspider ID5880
    KEGG Compound IDC00123
    BioCyc IDLEU
    BiGG ID33942
    Wikipedia LinkLeucine
    NuGOwiki LinkHMDB00687
    Metagene LinkHMDB00687
    METLIN ID24
    PubChem Compound6106
    PDB IDLEU
    ChEBI ID15603
    References
    Synthesis ReferenceLeuchtenberger, Wolfgang; Karrenbauer, Michael; Ploecker, Ulf. Scale-up of an enzyme membrane reactor process for the manufacture of L-enantiomeric compounds. Annals of the New York Academy of Sciences (1984), 434(Enzyme Eng.), 78-86.
    Material Safety Data Sheet (MSDS)Not Available
    General References
    1. Sreekumar A, Poisson LM, Rajendiran TM, Khan AP, Cao Q, Yu J, Laxman B, Mehra R, Lonigro RJ, Li Y, Nyati MK, Ahsan A, Kalyana-Sundaram S, Han B, Cao X, Byun J, Omenn GS, Ghosh D, Pennathur S, Alexander DC, Berger A, Shuster JR, Wei JT, Varambally S, Beecher C, Chinnaiyan AM: Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression. Nature. 2009 Feb 12;457(7231):910-4. Pubmed: 19212411
    2. Nicholson JK, O'Flynn MP, Sadler PJ, Macleod AF, Juul SM, Sonksen PH: Proton-nuclear-magnetic-resonance studies of serum, plasma and urine from fasting normal and diabetic subjects. Biochem J. 1984 Jan 15;217(2):365-75. Pubmed: 6696735
    3. Hagenfeldt L, Bjerkenstedt L, Edman G, Sedvall G, Wiesel FA: Amino acids in plasma and CSF and monoamine metabolites in CSF: interrelationship in healthy subjects. J Neurochem. 1984 Mar;42(3):833-7. Pubmed: 6198473
    4. Peng CT, Wu KH, Lan SJ, Tsai JJ, Tsai FJ, Tsai CH: Amino acid concentrations in cerebrospinal fluid in children with acute lymphoblastic leukemia undergoing chemotherapy. Eur J Cancer. 2005 May;41(8):1158-63. Epub 2005 Apr 14. Pubmed: 15911239
    5. Cynober LA: Plasma amino acid levels with a note on membrane transport: characteristics, regulation, and metabolic significance. Nutrition. 2002 Sep;18(9):761-6. Pubmed: 12297216
    6. Rainesalo S, Keranen T, Palmio J, Peltola J, Oja SS, Saransaari P: Plasma and cerebrospinal fluid amino acids in epileptic patients. Neurochem Res. 2004 Jan;29(1):319-24. Pubmed: 14992292
    7. Deng C, Shang C, Hu Y, Zhang X: Rapid diagnosis of phenylketonuria and other aminoacidemias by quantitative analysis of amino acids in neonatal blood spots by gas chromatography-mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2002 Jul 25;775(1):115-20. Pubmed: 12101068
    8. Yoshimasa T, Nakao K, Ohtsuki H, Li S, Imura H: Methionine-enkephalin and leucine-enkephalin in human sympathoadrenal system and pheochromocytoma. J Clin Invest. 1982 Mar;69(3):643-50. Pubmed: 7061706
    9. Jansson T, Scholtbach V, Powell TL: Placental transport of leucine and lysine is reduced in intrauterine growth restriction. Pediatr Res. 1998 Oct;44(4):532-7. Pubmed: 9773842
    10. Lichtenstein AH, Hachey DL, Millar JS, Jenner JL, Booth L, Ordovas J, Schaefer EJ: Measurement of human apolipoprotein B-48 and B-100 kinetics in triglyceride-rich lipoproteins using [5,5,5-2H3]leucine. J Lipid Res. 1992 Jun;33(6):907-14. Pubmed: 1512514
    11. Mero A: Leucine supplementation and intensive training. Sports Med. 1999 Jun;27(6):347-58. Pubmed: 10418071
    12. Sakamoto M, Nakao K, Yoshimasa T, Ikeda Y, Suda M, Takasu K, Shimbo S, Yanaihara N, Imura H: Occurrence of methionine-enkephalin-Arg6-Gly7-Leu8 with methionine-enkephalin, leucine-enkephalin and methionine-enkephalin-Arg6-Phe7 in human gastric antrum. J Clin Endocrinol Metab. 1983 Jan;56(1):202-4. Pubmed: 6847871
    13. Yudkoff M, Daikhin Y, Nissim I, Horyn O, Luhovyy B, Lazarow A, Nissim I: Brain amino acid requirements and toxicity: the example of leucine. J Nutr. 2005 Jun;135(6 Suppl):1531S-8S. Pubmed: 15930465
    14. Iannoli P, Miller JH, Wang HT, Bode B, Souba WW, Avissar NE, Sax HC: Characterization of L-leucine transport system in brush border membranes from human and rabbit small intestine. Metabolism. 1999 Nov;48(11):1432-6. Pubmed: 10582553

    Enzymes

    Gene Name:
    BCAT1
    Uniprot ID:
    P54687
    Reactions
    L-Leucine + Oxoglutaric acid unknown Ketoleucine + L-Glutamic aciddetails
    Gene Name:
    BCAT2
    Uniprot ID:
    O15382
    Reactions
    L-Leucine + Oxoglutaric acid unknown Ketoleucine + L-Glutamic aciddetails
    Gene Name:
    LARS2
    Uniprot ID:
    Q15031
    Reactions
    Adenosine triphosphate + L-Leucine + tRNA(Leu) unknown Adenosine monophosphate + Pyrophosphate + L-leucyl-tRNA(Leu)details
    Adenosine triphosphate + L-Leucine + tRNA(Leu) unknown Adenosine monophosphate + Pyrophosphate + L-Leucyl-tRNAdetails
    Gene Name:
    LARS
    Uniprot ID:
    Q9P2J5
    Reactions
    Adenosine triphosphate + L-Leucine + tRNA(Leu) unknown Adenosine monophosphate + Pyrophosphate + L-leucyl-tRNA(Leu)details
    Adenosine triphosphate + L-Leucine + tRNA(Leu) unknown Adenosine monophosphate + Pyrophosphate + L-Leucyl-tRNAdetails
    Gene Name:
    SLC3A2
    Uniprot ID:
    P08195
    Gene Name:
    LCMT2
    Uniprot ID:
    O60294
    Gene Name:
    LCMT1
    Uniprot ID:
    Q9UIC8

    Transporters