Human Metabolome Database Version 3.5

Showing metabocard for L-Leucine (HMDB00687)

Record Information
Version 3.5
Creation Date 2005-11-16 08:48:42 -0700
Update Date 2013-02-08 17:09:06 -0700
HMDB ID HMDB00687
Secondary Accession Numbers None
Metabolite Identification
Common Name L-Leucine
Description Branched 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
Download: MOL | SDF | PDB | SMILES | InChI
Display: 2D Structure | 3D Structure
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 Formula C6H13NO2
Average Molecular Weight 131.1729
Monoisotopic Molecular Weight 131.094628665
IUPAC Name (2S)-2-amino-4-methylpentanoic acid
Traditional IUPAC Name D-leucine
CAS Registry Number 61-90-5
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 Key ROHFNLRQFUQHCH-YFKPBYRVSA-N
Chemical Taxonomy
Kingdom Organic Compounds
Super Class Amino Acids, Peptides, and Analogues
Class Amino Acids and Derivatives
Sub Class Alpha 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 Parent Alpha Amino Acids and Derivatives
Ontology
Status Detected and Quantified
Origin
  • Drug
  • Food
Biofunction
  • Essential amino acids
  • Protein component
Application Not Available
Cellular locations
  • Extracellular
  • Mitochondria
Physical Properties
State Solid
Experimental Properties
Property Value Reference
Melting Point 268 - 288 °C Not Available
Boiling Point Not Available Not Available
Water Solubility 21.5 mg/mL Not Available
LogP -1.52 HANSCH,C ET AL. (1995)
Predicted Properties
Property Value Source
Water Solubility 69.8 g/L ALOGPS
LogP -1.82 ALOGPS
LogP -1.6 ChemAxon
LogS -0.27 ALOGPS
pKa (strongest acidic) 2.79 ChemAxon
pKa (strongest basic) 9.52 ChemAxon
Hydrogen Acceptor Count 3 ChemAxon
Hydrogen Donor Count 2 ChemAxon
Polar Surface Area 63.32 A2 ChemAxon
Rotatable Bond Count 3 ChemAxon
Refractivity 34.17 ChemAxon
Polarizability 14.25 ChemAxon
Formal Charge 0 ChemAxon
Physiological Charge 0 ChemAxon
Spectra
Gas-MS Spectrum
13C NMR Spectrum
1H NMR Spectrum
MS/MS Spectrum Quattro_QQQ 10
MS/MS Spectrum Quattro_QQQ 25
MS/MS Spectrum Quattro_QQQ 40
MS/MS Spectrum EI-B (HITACHI M-80)
MS/MS Spectrum LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic)
MS/MS Spectrum LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic)
MS/MS Spectrum LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic)
MS/MS Spectrum LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic)
MS/MS Spectrum LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic)
MS/MS Spectrum LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic)
MS/MS Spectrum LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic)
MS/MS Spectrum LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic)
MS/MS Spectrum LC-ESI-QQ (API3000, Applied Biosystems) 10
MS/MS Spectrum LC-ESI-QQ (API3000, Applied Biosystems) 20
MS/MS Spectrum LC-ESI-QQ (API3000, Applied Biosystems) 30
[1H,13C] 2D NMR Spectrum
Biological Properties
Cellular Locations
  • Extracellular
  • Mitochondria
Biofluid Locations
  • Blood
  • Cerebrospinal Fluid (CSF)
  • Urine
Tissue Location
  • Muscle
  • Skeletal Muscle
  • Bladder
  • Fibroblasts
  • Intestine
  • Neuron
  • Placenta
  • Testes
  • Kidney
  • Epidermis
  • Prostate
  • Adipose Tissue
  • Adrenal Medulla
  • Nerve Cells
  • Platelet
Pathways
Name SMPDB Link KEGG Link
Valine, Leucine and Isoleucine Degradation SMP00032 map00280 Link_out
Transcription/Translation SMP00019 Not Available
Normal Concentrations
Biofluid Status Value Age Sex Condition Reference
Blood Detected and Quantified
70.0 +/- 25.0 uM Newborn (0-30 days old) Not Specified Normal
  • Geigy Scient...
Blood Detected and Quantified
134.0 +/- 20.0 uM Children (1-13 year old) Male Normal
  • Geigy Scient...
Blood Detected and Quantified
160.0 +/- 27.0 uM Adult (>18 years old) Female Normal
  • Geigy Scient...
Blood Detected and Quantified
157.0 +/- 30.0 uM Adult (>18 years old) Male Normal
  • Geigy Scient...
Blood Detected and Quantified
123 (98-148) uM Adult (>18 years old) Both Normal
Blood Detected and Quantified
251 +/- 5 uM Adult (>18 years old) Both Normal
Blood Detected and Quantified
98.7 +/- 11.5 uM Adult (>18 years old) Not Specified Normal
Cerebrospinal Fluid (CSF) Detected and Quantified
16 +/- 9 uM Not Specified Both Normal
Cerebrospinal Fluid (CSF) Detected and Quantified
10.1 +/- 2.1 uM Adult (>18 years old) Both Normal
  • Geigy Scient...
Cerebrospinal Fluid (CSF) Detected and Quantified
14.5 +/- 3.7 uM Adult (>18 years old) Not Specified Normal
Cerebrospinal Fluid (CSF) Detected and Quantified
18.6 +/- 4.1 uM Adult (>18 years old) Not Specified Normal
Cerebrospinal Fluid (CSF) Detected and Quantified
11.2 +/- 3.5 uM Adult (>18 years old) Not Specified Normal
Urine Detected and Quantified
3.5 umol/mmol creatinine Adult (>18 years old) Both Normal
Urine Detected and Quantified
6.10-19.07 umol/mmol creatinine Adult (>18 years old) Both Normal
  • David F. Put...
Urine Detected and Quantified
7.58 +/- 4.10 umol/mmol creatinine Infant (0-1 year old) Both Normal
Urine Detected and Quantified
4.868 (1.842-8.421) umol/mmol creatinine Adult (>18 years old) Both Normal
Urine Detected but not Quantified
Not Applicable Adult (>18 years old) Both Comment Normal
Urine Detected and Quantified
0.1 (0.0-0.2) umol/mmol creatinine Newborn (0-30 days old) Both Normal
  • Geigy Scient...
  • West Cadwell...
  • Basel, Switz...
Urine Detected and Quantified
2.5 +/- 1.0 umol/mmol creatinine Children (1-13 year old) Male Normal
  • Geigy Scient...
  • West Cadwell...
  • Basel, Switz...
Urine Detected and Quantified
3.0+/- 1.5 umol/mmol creatinine Adult (>18 years old) Male Normal
  • Geigy Scient...
  • West Cadwell...
  • Basel, Switz...
Urine Detected and Quantified
2.5 +/- 1.3 umol/mmol creatinine Adult (>18 years old) Female Normal
  • Geigy Scient...
  • West Cadwell...
  • Basel, Switz...
Urine Detected and Quantified
3.0 (1.6-6.0) umol/mmol creatinine Adult (>18 years old) Both Comment Normal
Urine Detected and Quantified
2.8 (1.6-5.4) umol/mmol creatinine Adult (>18 years old) Both Comment Normal
Urine Detected and Quantified
1.2 umol/mmol creatinine Adult (>18 years old) Both Normal
Abnormal Concentrations
Biofluid Status Value Age Sex Condition Reference
Blood Detected and Quantified 74.8 +/- 34.3 uM Adult (>18 years old) Not Specified Heart Transplant
Blood Detected and Quantified 66.0 +/- 161.0 uM Newborn (0-30 days old) Both Phenylketonuria (PKU)
Blood Detected and Quantified 95.3 (89.3-100.0) uM Adult (>18 years old) Both Comment Epilepsy
Blood Detected and Quantified 273.0 +/- 10.0 uM Adult (>18 years old) Both Comment Heart failure
Blood Detected and Quantified 103.0 (97.8-108.0) uM Adult (>18 years old) Both Comment Epilepsy
Blood Detected and Quantified 643.0 +/- 667.0 uM Newborn (0-30 days old) Both Maple syrup urine disease (MSUD)
Cerebrospinal Fluid (CSF) Detected and Quantified 11.5 +/- 1.5 uM Adult (>18 years old) Both Alzheimer's disease
Cerebrospinal Fluid (CSF) Detected and Quantified 16.5 +/- 7.0 uM Children (1-13 year old) Not Specified Comment Leukemia
Cerebrospinal Fluid (CSF) Detected and Quantified 13.1 +/- 5.6 uM Children (1-13 year old) Not Specified Leukemia
Urine Detected and Quantified 0.91 +/- 0.11 umol/mmol creatinine Adult (>18 years old) Both Alzheimer's disease
Associated Disorders and Diseases
Disease References
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 Link_out
      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 Link_out
          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 Link_out
              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 Link_out
                  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 Link_out
                      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 Link_out
                          Associated OMIM IDs
                          DrugBank ID Not Available
                          DrugBank Metabolite ID Not Available
                          Phenol Explorer Compound ID Not Available
                          Phenol Explorer Metabolite ID Not Available
                          FoodDB ID FDB001946
                          KNApSAcK ID C00001377 Link_out
                          Chemspider ID 5880 Link_out
                          KEGG Compound ID C00123 Link_out
                          BioCyc ID LEU Link_out
                          BiGG ID 33942 Link_out
                          Wikipedia Link Leucine Link_out
                          NuGOwiki Link HMDB00687 Link_out
                          Metagene Link HMDB00687 Link_out
                          METLIN ID 24 Link_out
                          PubChem Compound 6106 Link_out
                          PDB ID LEU Link_out
                          ChEBI ID 15603 Link_out
                          References
                          Synthesis Reference Leuchtenberger, 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) Download (PDF)
                          General References
                          1. 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 Link_out
                          2. 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 Link_out
                          3. 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 Link_out
                          4. 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 Link_out
                          5. 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 Link_out
                          6. 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 Link_out
                          7. 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 Link_out
                          8. 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 Link_out
                          9. Mero A: Leucine supplementation and intensive training. Sports Med. 1999 Jun;27(6):347-58. Pubmed: 10418071 Link_out
                          10. 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 Link_out
                          11. 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 Link_out
                          12. 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 Link_out
                          13. 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 Link_out
                          14. 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 Link_out

                          Enzymes
                          Name: Branched-chain-amino-acid aminotransferase, cytosolic
                          Reactions:
                          L-Leucine + Oxoglutaric acid unknown Ketoleucine + L-Glutamic acid details
                          Gene Name: BCAT1
                          Uniprot ID: P54687 Link_out
                          Protein Sequence: FASTA
                          Gene Sequence: FASTA
                          Name: Branched-chain-amino-acid aminotransferase, mitochondrial
                          Reactions:
                          L-Leucine + Oxoglutaric acid unknown Ketoleucine + L-Glutamic acid details
                          Gene Name: BCAT2
                          Uniprot ID: O15382 Link_out
                          Protein Sequence: FASTA
                          Gene Sequence: FASTA
                          Name: Probable leucine--tRNA ligase, mitochondrial
                          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-tRNA details
                          Gene Name: LARS2
                          Uniprot ID: Q15031 Link_out
                          Protein Sequence: FASTA
                          Gene Sequence: FASTA
                          Name: Leucine--tRNA ligase, cytoplasmic
                          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-tRNA details
                          Gene Name: LARS
                          Uniprot ID: Q9P2J5 Link_out
                          Protein Sequence: FASTA
                          Gene Sequence: FASTA
                          Name: 4F2 cell-surface antigen heavy chain
                          Reactions: Not Available
                          Gene Name: SLC3A2
                          Uniprot ID: P08195 Link_out
                          Protein Sequence: FASTA
                          Gene Sequence: FASTA
                          Name: Leucine carboxyl methyltransferase 2
                          Reactions: Not Available
                          Gene Name: LCMT2
                          Uniprot ID: O60294 Link_out
                          Protein Sequence: FASTA
                          Gene Sequence: FASTA
                          Name: Leucine carboxyl methyltransferase 1
                          Reactions: Not Available
                          Gene Name: LCMT1
                          Uniprot ID: Q9UIC8 Link_out
                          Protein Sequence: FASTA
                          Gene Sequence: FASTA
                          Transporters
                          Name: Large neutral amino acids transporter small subunit 2
                          Reactions: Not Available
                          Gene Name: SLC7A8
                          Uniprot ID: Q9UHI5 Link_out
                          Protein Sequence: FASTA
                          Gene Sequence: FASTA