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Record Information
Version3.6
Creation Date2005-11-16 15:48:42 UTC
Update Date2016-06-10 21:22:31 UTC
HMDB IDHMDB00099
Secondary Accession Numbers
  • HMDB03614
Metabolite Identification
Common NameL-Cystathionine
DescriptionCystathionine is a dipeptide formed by serine and homocysteine. Cystathioninuria is a prominent manifestation of vitamin-B6 deficiency. The transsulfuration of methionine yields homocysteine, which combines with serine to form cystathionine, the proximate precursor of cysteine through the enzymatic activity of cystathionase. In conditions in which cystathionine gamma-synthase or cystathionase is deficient, for example, there is cystathioninuria. Although cystathionine has not been detected in normal human serum or plasma by most conventional methods, gas chromatographic/mass spectrometric methodology detected a mean concentration of cystathionine in normal human serum of 140 nM, with a range of 65 to 301 nM.567 Cystathionine concentrations in CSF have been 10, 1, and 0.5 uM, and "not detected." Only traces (i.e., <1 uM) of cystathionine are present in normal CSF.587. gamma-Cystathionase deficiency provided the first instance in which, in a human, the major biochemical abnormality due to a defined enzyme defect was clearly shown to be alleviated by administration of large doses of pyridoxine. The response in gamma-cystathionase-deficient patients is not attributable to correction of a preexisting deficiency of this vitamin. (OMMBID, Chap. 88).
Structure
Thumb
Synonyms
ValueSource
(R)-S-(2-amino-2-Carboxyethyl)-L-homocysteineChEBI
L-(+)-CystathionineChEBI
S-(beta-amino-beta-Carboxyethyl)homocysteineChEBI
CystathionineHMDB
S-[(2R)-2-amino-2-Carboxyethyl]-L-homocysteineHMDB
[R-(R*,s*)]-2-amino-4-[(2-amino-2-carboxyethyl)thio]-butanoateHMDB
[R-(R*,s*)]-2-amino-4-[(2-amino-2-carboxyethyl)thio]-butanoic acidHMDB
Chemical FormulaC7H14N2O4S
Average Molecular Weight222.262
Monoisotopic Molecular Weight222.067427636
IUPAC Name(2S)-2-amino-4-{[(2R)-2-amino-2-carboxyethyl]sulfanyl}butanoic acid
Traditional NameL-cystathionine
CAS Registry Number56-88-2
SMILES
N[C@@H](CCSC[C@H](N)C(O)=O)C(O)=O
InChI Identifier
InChI=1S/C7H14N2O4S/c8-4(6(10)11)1-2-14-3-5(9)7(12)13/h4-5H,1-3,8-9H2,(H,10,11)(H,12,13)/t4-,5-/m0/s1
InChI KeyInChIKey=ILRYLPWNYFXEMH-WHFBIAKZSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as s-alkyl-l-cysteines. These are cysteine derivatives that carry an alkyl chain attached to the sulfanyl group.
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassCarboxylic acids and derivatives
Sub ClassAmino acids, peptides, and analogues
Direct ParentS-alkyl-L-cysteines
Alternative Parents
Substituents
  • S-alkyl-l-cysteine
  • D-alpha-amino acid
  • Thia fatty acid
  • Amino fatty acid
  • Fatty acyl
  • Fatty acid
  • Dicarboxylic acid or derivatives
  • Dialkylthioether
  • Sulfenyl compound
  • Thioether
  • Carboxylic acid
  • Hydrocarbon derivative
  • Primary amine
  • Organosulfur compound
  • Organooxygen compound
  • Organonitrogen compound
  • Primary aliphatic amine
  • Carbonyl group
  • Amine
  • Aliphatic acyclic compound
Molecular FrameworkAliphatic acyclic compounds
External Descriptors
Ontology
StatusDetected and Quantified
Origin
  • Drug metabolite
  • Endogenous
Biofunction
  • Component of Cysteine metabolism
  • Component of Glycine, serine and threonine metabolism
  • Component of Methionine metabolism
  • Component of Nitrogen metabolism
  • Component of Selenoamino acid metabolism
  • Waste products
ApplicationNot Available
Cellular locations
  • Cytoplasm (predicted from logP)
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point312 °CNot Available
Boiling PointNot AvailableNot Available
Water Solubility22 mg/mLNot Available
LogPNot AvailableNot Available
Predicted Properties
PropertyValueSource
Water Solubility17.3 mg/mLALOGPS
logP-4ALOGPS
logP-5.8ChemAxon
logS-1.1ALOGPS
pKa (Strongest Acidic)1.79ChemAxon
pKa (Strongest Basic)9.66ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count4ChemAxon
Polar Surface Area126.64 Å2ChemAxon
Rotatable Bond Count7ChemAxon
Refractivity51.57 m3·mol-1ChemAxon
Polarizability22.02 Å3ChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
GC-MSGC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (4 TMS)splash10-00fr-8950000000-640b4294e37e5a01048dView in MoNA
GC-MSGC-MS Spectrum - GC-MS (2 TMS)splash10-0f7c-7910000000-91f9f2b2dd44a3cdb276View in MoNA
GC-MSGC-MS Spectrum - GC-MS (3 TMS)splash10-00or-1940000000-c0d688e4ea87ff3e03faView in MoNA
GC-MSGC-MS Spectrum - GC-MS (4 TMS)splash10-00or-0980000000-7d816de782a902900d0eView in MoNA
GC-MSGC-MS Spectrum - GC-MSNot Available
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)splash10-0089-1980000000-99cb7d1da067e5436b09View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)splash10-000i-9200000000-fb776970b6ef36e72725View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)splash10-000i-9200000000-fb776970b6ef36e72725View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 10V, Positivesplash10-00fr-0690000000-0b572de3fcbc7e2f13ccView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 20V, Positivesplash10-000t-0900000000-5788192b32aadd177e33View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 30V, Positivesplash10-000b-4900000000-b86ac7de446a762365bdView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 40V, Positivesplash10-000j-9800000000-75ff1bc6e325692a9da9View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 50V, Positivesplash10-00kr-9100000000-6517562dc0f31a85afc8View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-IT (LC/MSD Trap XCT, Agilent Technologies) , Positivesplash10-001i-0900000000-d1628d0a880f1b6e6d90View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-IT (LC/MSD Trap XCT, Agilent Technologies) , Positivesplash10-000i-9000000000-9a2e1e54b77216e2df72View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF (UPLC Q-Tof Premier, Waters) , Positivesplash10-00di-0090000000-36678c2f0bf1b01cc9d4View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF (UPLC Q-Tof Premier, Waters) 30V, Positivesplash10-05fr-0190000000-e575f57f0d76ef6afa49View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF (UPLC Q-Tof Premier, Waters) , Negativesplash10-00e9-0940000000-962ae510f06296b98878View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
1D NMR1H NMR SpectrumNot Available
2D NMR[1H,13C] 2D NMR SpectrumNot Available
Biological Properties
Cellular Locations
  • Cytoplasm (predicted from logP)
Biofluid Locations
  • Blood
  • Cerebrospinal Fluid (CSF)
  • Urine
Tissue Location
  • Brain
  • Kidney
  • Liver
  • Prostate
Pathways
NameSMPDB LinkKEGG Link
3-Phosphoglycerate dehydrogenase deficiencySMP00721Not Available
Cystathionine Beta-Synthase DeficiencySMP00177Not Available
Dihydropyrimidine Dehydrogenase Deficiency (DHPD)SMP00179Not Available
Dimethylglycine Dehydrogenase DeficiencySMP00242Not Available
Dimethylglycine Dehydrogenase DeficiencySMP00484Not Available
Gamma-cystathionase deficiency (CTH)SMP00514Not Available
Glycine and Serine MetabolismSMP00004map00260
Glycine N-methyltransferase DeficiencySMP00222Not Available
Homocysteine DegradationSMP00455Not Available
Homocystinuria, cystathionine beta-synthase deficiencySMP00515Not Available
Homocystinuria-megaloblastic anemia due to defect in cobalamin metabolism, cblG complementation typeSMP00570Not Available
Hyperglycinemia, non-ketoticSMP00485Not Available
HypermethioninemiaSMP00341Not Available
Methionine Adenosyltransferase DeficiencySMP00221Not Available
Methionine MetabolismSMP00033map00270
Methylenetetrahydrofolate Reductase Deficiency (MTHFRD)SMP00340Not Available
Non Ketotic HyperglycinemiaSMP00223Not Available
S-Adenosylhomocysteine (SAH) Hydrolase DeficiencySMP00214Not Available
SarcosinemiaSMP00244Not Available
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified0.329 (0.150-0.661) uMAdult (>18 years old)BothNormal details
BloodDetected and Quantified0.17 (0.1 – 0.27) uMChildren (1-13 years old)BothNormal details
BloodDetected and Quantified1.0 (0.3-5.5) uMNewborn (0-30 days old)BothNormal
    • Geigy Scientific ...
details
BloodDetected and Quantified0.126 (0.065 - 0.301) uMAdult (>18 years old)BothNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified0.024 +/- 0.006 uMChildren (1-13 years old)BothNormal details
UrineDetected and Quantified1.84 (0.39-3.28) umol/mmol creatinineAdult (>18 years old)BothNormal
    details
    UrineDetected and Quantified0.94-2.3 umol/mmol creatinineAdult (>18 years old)FemaleNormal details
    UrineDetected and Quantified14.7 (3.9-20.7) umol/mmol creatinineAdult (>18 years old)Both
    Normal
    details
    UrineDetected and Quantified0.80-1.6 umol/mmol creatinineAdult (>18 years old)MaleNormal details
    UrineDetected and Quantified1.54 ± 1.09 umol/mmol creatinineAdult (>18 years old)BothNormal details
    UrineDetected and Quantified0.35 +/- 0.65 umol/mmol creatinineInfant (0-1 year old)BothNormal details
    Abnormal Concentrations
    BiofluidStatusValueAgeSexConditionReferenceDetails
    BloodDetected and Quantified1.56 (0.14 - 4.1) uMAdult (>18 years old)BothFolate Deficiency details
    BloodDetected and Quantified0.82 (0.21 - 2.9) uMAdult (>18 years old)BothCobalamin Deficiency details
    BloodDetected and Quantified0.14 (0.04-0.2) uMChildren (1-13 years old)BothAutism details
    BloodDetected and Quantified1.03 +/- 0.22 uMElderly (>65 years old)BothAlzheimer's disease details
    UrineDetected and Quantified381.0 +/- 29.0 umol/mmol creatinineAdult (>18 years old)BothCystathioninuria details
    UrineDetected and Quantified5.3 (1.0-9.6) umol/mmol creatinineAdult (>18 years old)BothCystathioninuria details
    UrineDetected and Quantified1001.0 (158.0-1843.8) umol/mmol creatinineChildren (1-13 years old)BothGamma-Cystathionase deficiency details
    UrineDetected and Quantified12.677 +/- 3.531 umol/mmol creatinineChildren (1 - 13 years old)Not Specified
    Eosinophilic esophagitis
      • Mordechai, Hien, ...
    details
    UrineDetected and Quantified1.68 +/- 0.5 umol/mmol creatinineAdult (>18 years old)BothAlzheimer's disease details
    Associated Disorders and Diseases
    Disease References
    Alzheimer's disease
    1. 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. [17031479 ]
    Autism
    1. James SJ, Cutler P, Melnyk S, Jernigan S, Janak L, Gaylor DW, Neubrander JA: Metabolic biomarkers of increased oxidative stress and impaired methylation capacity in children with autism. Am J Clin Nutr. 2004 Dec;80(6):1611-7. [15585776 ]
    Vitamin B12 deficiency
    1. Stabler SP, Lindenbaum J, Savage DG, Allen RH: Elevation of serum cystathionine levels in patients with cobalamin and folate deficiency. Blood. 1993 Jun 15;81(12):3404-13. [8507876 ]
    Cystathioninuria
    1. Sugahara K, Ohta J, Takemura M, Kodama H: Determination of cystathionine and perhydro-1,4-thiazepine-3,5-dicarboxylic acid in the urine of a patient with cystathioninuria using column liquid chromatography-mass spectrometry. J Chromatogr. 1992 Sep 2;579(2):318-23. [1429979 ]
    2. MetaGene [Link]
    Folate deficiency
    1. Stabler SP, Lindenbaum J, Savage DG, Allen RH: Elevation of serum cystathionine levels in patients with cobalamin and folate deficiency. Blood. 1993 Jun 15;81(12):3404-13. [8507876 ]
    Associated OMIM IDs
    DrugBank IDNot Available
    DrugBank Metabolite IDDBMET00486
    Phenol Explorer Compound IDNot Available
    Phenol Explorer Metabolite IDNot Available
    FoodDB IDFDB001976
    KNApSAcK IDC00007498
    Chemspider ID388392
    KEGG Compound IDC02291
    BioCyc IDL-CYSTATHIONINE
    BiGG ID39523
    Wikipedia LinkCystathionine
    NuGOwiki LinkHMDB00099
    Metagene LinkHMDB00099
    METLIN ID39
    PubChem Compound439258
    PDB IDNot Available
    ChEBI ID17482
    References
    Synthesis ReferenceYamagata, Shuzo; Akamatsu, Tsuyoshi; Iwama, Tomonori. Immobilization of Saccharomyces cerevisiae cystathionine gamma-lyase and application of the product to cystathionine synthesis. Applied and Environmental Microbiology (2004), 70(6), 3766-3768.
    Material Safety Data Sheet (MSDS)Download (PDF)
    General References
    1. Kraus JP, Janosik M, Kozich V, Mandell R, Shih V, Sperandeo MP, Sebastio G, de Franchis R, Andria G, Kluijtmans LA, Blom H, Boers GH, Gordon RB, Kamoun P, Tsai MY, Kruger WD, Koch HG, Ohura T, Gaustadnes M: Cystathionine beta-synthase mutations in homocystinuria. Hum Mutat. 1999;13(5):362-75. [10338090 ]
    2. 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. [19212411 ]
    3. Shoemaker JD, Elliott WH: Automated screening of urine samples for carbohydrates, organic and amino acids after treatment with urease. J Chromatogr. 1991 Jan 2;562(1-2):125-38. [2026685 ]
    4. Ricci G, Santoro L, Achilli M, Matarese RM, Nardini M, Cavallini D: Similarity of the oxidation products of L-cystathionine by L-amino acid oxidase to those excreted by cystathioninuric patients. J Biol Chem. 1983 Sep 10;258(17):10511-7. [6885789 ]
    5. Herrmann W, Schorr H, Bodis M, Knapp JP, Muller A, Stein G, Geisel J: Role of homocysteine, cystathionine and methylmalonic acid measurement for diagnosis of vitamin deficiency in high-aged subjects. Eur J Clin Invest. 2000 Dec;30(12):1083-9. [11122323 ]
    6. Stabler SP, Lindenbaum J, Savage DG, Allen RH: Elevation of serum cystathionine levels in patients with cobalamin and folate deficiency. Blood. 1993 Jun 15;81(12):3404-13. [8507876 ]
    7. Lefauconnier JM, Portemer C, Chatagner F: Free amino acids and related substances in human glial tumours and in fetal brain: comparison with normal adult brain. Brain Res. 1976 Nov 19;117(1):105-13. [186155 ]
    8. James SJ, Cutler P, Melnyk S, Jernigan S, Janak L, Gaylor DW, Neubrander JA: Metabolic biomarkers of increased oxidative stress and impaired methylation capacity in children with autism. Am J Clin Nutr. 2004 Dec;80(6):1611-7. [15585776 ]
    9. Shimizu H, Kakimoto Y, Sano I: A method of determination of cystathionine and its distribution in human brain. J Neurochem. 1966 Feb;13(2):65-73. [5936154 ]
    10. Haurani FI, Hall CA, Rubin R: Megaloblastic anemia as a result of an abnormal transcobalamin II (Cardeza). J Clin Invest. 1979 Nov;64(5):1253-9. [500809 ]
    11. Wisniewski K, Sturman JA, Devine E, Brown WT, Rudelli R, Wisniewski HM: Cystathionine disappearance with neuronal loss: a possible neuronal marker. Neuropediatrics. 1985 Aug;16(3):126-30. [4047345 ]

    Enzymes

    General function:
    Involved in pyridoxal phosphate binding
    Specific function:
    Catalyzes the last step in the trans-sulfuration pathway from methionine to cysteine. Has broad substrate specificity. Converts cystathionine to cysteine, ammonia and 2-oxobutanoate. Converts two cysteine molecules to lanthionine and hydrogen sulfide. Can also accept homocysteine as substrate. Specificity depends on the levels of the endogenous substrates. Generates the endogenous signaling molecule hydrogen sulfide (H2S), and so contributes to the regulation of blood pressure. Acts as a cysteine-protein sulfhydrase by mediating sulfhydration of target proteins: sulfhydration consists of converting -SH groups into -SSH on specific cysteine residues of target proteins such as GAPDH, PTPN1 and NF-kappa-B subunit RELA, thereby regulating their function.
    Gene Name:
    CTH
    Uniprot ID:
    P32929
    Molecular weight:
    41259.91
    Reactions
    L-Cystathionine + Water → L-Cysteine + Ammonia + 2-Ketobutyric aciddetails
    General function:
    Involved in cysteine biosynthetic process from serine
    Specific function:
    Only known pyridoxal phosphate-dependent enzyme that contains heme. Important regulator of hydrogen sulfide, especially in the brain, utilizing cysteine instead of serine to catalyze the formation of hydrogen sulfide. Hydrogen sulfide is a gastratransmitter with signaling and cytoprotective effects such as acting as a neuromodulator in the brain to protect neurons against hypoxic injury (By similarity).
    Gene Name:
    CBS
    Uniprot ID:
    P35520
    Molecular weight:
    60586.05
    Reactions
    L-Serine + Homocysteine → L-Cystathionine + Waterdetails