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Human Metabolome Database Version 3.5

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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 | 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
  • Food
  • Drug
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 Comments
Blood Detected and Quantified
Article_icon
70.0 +/- 25.0 uM Newborn (0-30 days old) Not Specified Normal Not Available
Blood Detected and Quantified
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134.0 +/- 20.0 uM Children (1-13 year old) Male Normal Not Available
Blood Detected and Quantified
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160.0 +/- 27.0 uM Adult (>18 years old) Female Normal Not Available
Blood Detected and Quantified
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157.0 +/- 30.0 uM Adult (>18 years old) Male Normal Not Available
Blood Detected and Quantified
Article_icon
123 (98-148) uM Adult (>18 years old) Both Normal Not Available
Blood Detected and Quantified
Article_icon
251 +/- 5 uM Adult (>18 years old) Both Normal Not Available
Blood Detected and Quantified
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98.7 +/- 11.5 uM Adult (>18 years old) Not Specified Normal Not Available
Cerebrospinal Fluid (CSF) Detected and Quantified
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16 +/- 9 uM Not Specified Both Normal Not Available
Cerebrospinal Fluid (CSF) Detected and Quantified
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10.1 +/- 2.1 uM Adult (>18 years old) Both Normal Not Available
Cerebrospinal Fluid (CSF) Detected and Quantified
Article_icon
14.5 +/- 3.7 uM Adult (>18 years old) Not Specified Normal Not Available
Cerebrospinal Fluid (CSF) Detected and Quantified
Article_icon
18.6 +/- 4.1 uM Adult (>18 years old) Not Specified Normal Not Available
Cerebrospinal Fluid (CSF) Detected and Quantified
Article_icon
11.2 +/- 3.5 uM Adult (>18 years old) Not Specified Normal Not Available
Urine Detected and Quantified
Article_icon
3.5 umol/mmol creatinine Adult (>18 years old) Both Normal Not Available
Urine Detected and Quantified
Article_icon
6.10-19.07 umol/mmol creatinine Adult (>18 years old) Both Normal Not Available
Urine Detected and Quantified
Article_icon
7.58 +/- 4.10 umol/mmol creatinine Infant (0-1 year old) Both Normal Not Available
Urine Detected and Quantified
Article_icon
4.868 (1.842-8.421) umol/mmol creatinine Adult (>18 years old) Both Normal Not Available
Urine Detected and not Quantified
Article_icon
Not Applicable Adult (>18 years old) Both Normal Urine compound detected by GC-MS
Urine Detected and Quantified
Article_icon
0.1 (0.0-0.2) umol/mmol creatinine Newborn (0-30 days old) Both Normal Not Available
Urine Detected and Quantified
Article_icon
2.5 +/- 1.0 umol/mmol creatinine Children (1-13 year old) Male Normal Not Available
Urine Detected and Quantified
Article_icon
3.0+/- 1.5 umol/mmol creatinine Adult (>18 years old) Male Normal Not Available
Urine Detected and Quantified
Article_icon
2.5 +/- 1.3 umol/mmol creatinine Adult (>18 years old) Female Normal Not Available
Urine Detected and Quantified
Article_icon
3.0 (1.6-6.0) umol/mmol creatinine Adult (>18 years old) Both Normal by LC-MS/MS (Biocrates kit)
Urine Detected and Quantified
Article_icon
2.8 (1.6-5.4) umol/mmol creatinine Adult (>18 years old) Both Normal urine by NMR
Urine Detected and Quantified
Article_icon
1.2 umol/mmol creatinine Adult (>18 years old) Both Normal Not Available
Abnormal Concentrations
Biofluid Status Value Age Sex Condition Comments
Blood Detected and Quantified
Article_icon
74.8 +/- 34.3 uM Adult (>18 years old) Not Specified Heart Transplant Not Available
Blood Detected and Quantified
Article_icon
66.0 +/- 161.0 uM Newborn (0-30 days old) Both Phenylketonuria (PKU) Not Available
Blood Detected and Quantified
Article_icon
95.3 (89.3-100.0) uM Adult (>18 years old) Both Epilepsy Refractory localization-related epilepsy (RLE)
Blood Detected and Quantified
Article_icon
273.0 +/- 10.0 uM Adult (>18 years old) Both Heart failure Non-diabetic patients with chronic heart failure
Blood Detected and Quantified
Article_icon
103.0 (97.8-108.0) uM Adult (>18 years old) Both Epilepsy Acute seizures
Blood Detected and Quantified
Article_icon
643.0 +/- 667.0 uM Newborn (0-30 days old) Both Maple syrup urine disease (MSUD) Not Available
Cerebrospinal Fluid (CSF) Detected and Quantified
Article_icon
11.5 +/- 1.5 uM Adult (>18 years old) Both Alzheimer's disease Not Available
Cerebrospinal Fluid (CSF) Detected and Quantified
Article_icon
16.5 +/- 7.0 uM Children (1-13 year old) Not Specified Leukemia Acute Lymphoblastic Leukemia (ALL) with Central...
Cerebrospinal Fluid (CSF) Detected and Quantified
Article_icon
13.1 +/- 5.6 uM Children (1-13 year old) Not Specified Leukemia Not Available
Urine Detected and Quantified
Article_icon
0.91 +/- 0.11 umol/mmol creatinine Adult (>18 years old) Both Alzheimer's disease Not Available
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
              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 + 2-oxoglutarate = 4-methyl-2-oxopentanoate + L-glutamate [RN:R01090]
              Gene Name: BCAT1
              Uniprot ID: P54687 Link_out
              Protein Sequence: FASTA
              Gene Sequence: FASTA
              Name: Branched-chain-amino-acid aminotransferase, mitochondrial
              Reactions:
              • L-leucine + 2-oxoglutarate = 4-methyl-2-oxopentanoate + L-glutamate [RN:R01090]
              Gene Name: BCAT2
              Uniprot ID: O15382 Link_out
              Protein Sequence: FASTA
              Gene Sequence: FASTA
              Name: Probable leucyl-tRNA synthetase, mitochondrial
              Reactions:
              • ATP + L-leucine + tRNALeu = AMP + diphosphate + L-leucyl-tRNALeu [RN:R03657]
              Gene Name: LARS2
              Uniprot ID: Q15031 Link_out
              Protein Sequence: FASTA
              Gene Sequence: FASTA
              Name: Leucyl-tRNA synthetase, cytoplasmic
              Reactions:
              • ATP + L-leucine + tRNALeu = AMP + diphosphate + L-leucyl-tRNALeu [RN:R03657]
              Gene Name: LARS
              Uniprot ID: Q9P2J5 Link_out
              Protein Sequence: FASTA
              Gene Sequence: FASTA
              Name: 4F2 cell-surface antigen heavy chain
              Reactions:
                Gene Name: SLC3A2
                Uniprot ID: P08195 Link_out
                Protein Sequence: FASTA
                Gene Sequence: FASTA
                Name: Leucine carboxyl methyltransferase 2
                Reactions:
                  Gene Name: LCMT2
                  Uniprot ID: O60294 Link_out
                  Protein Sequence: FASTA
                  Gene Sequence: FASTA
                  Name: Leucine carboxyl methyltransferase 1
                  Reactions:
                    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:
                    • --- []
                    Gene Name: SLC7A8
                    Uniprot ID: Q9UHI5 Link_out
                    Protein Sequence: FASTA
                    Gene Sequence: FASTA