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Record Information
Version4.0
StatusDetected but not Quantified
Creation Date2005-11-16 15:48:42 UTC
Update Date2018-03-28 17:01:10 UTC
HMDB IDHMDB0000279
Secondary Accession Numbers
  • HMDB00279
Metabolite Identification
Common NameSaccharopine
DescriptionSaccharopine is an intermediate in the degradation of lysine, formed by the condensation of lysine and alpha-ketoglutarate. The saccharopine pathway is the main route for lysine degradation in mammals, and its first two reactions are catalyzed by enzymatic activities known as lysine-oxoglutarate reductase (LOR) and saccharopine dehydrogenase (SDH), which reside on a single bifunctional polypeptide (LOR/SDH) (EC 1.5.1.8). The reactions involved with saccharopine dehydrogenases have very strict substrate specificity for L-lysine, 2-oxoglutarate, and NADPH. LOR/SDH has been detected in a number of mammalian tissues, mainly in the liver and kidney, contributing not only to the general nitrogen balance in the organism but also to the controlled conversion of lysine into ketone bodies. A tetrameric form has also been observed in human liver and placenta. LOR activity has also been detected in brain mitochondria during embryonic development, and this opens up the question of whether or not lysine degradation has any functional significance during brain development. As a result, there is now a new focus on the nutritional requirements for lysine in gestation and infancy. Finally, LOR and/or SDH deficiencies seem to be involved in a human autosomal genetic disorder known as familial hyperlysinemia, which is characterized by serious defects in the functioning of the nervous system and characterized by a deficiency in lysine-ketoglutarate reductase, saccharopine dehydrogenase, and saccharopine oxidoreductase activities. Saccharopinuria (high amounts of saccharopine in the urine) and saccharopinemia (an excess of saccharopine in the blood) are conditions present in some inherited disorders of lysine degradation (PMID: 463877 , 10567240 , 10772957 , 4809305 ). If present in sufficiently high levels, saccharopine can act as an acidogen and a metabotoxin. An acidogen is an acidic compound that induces acidosis, which has multiple adverse effects on many organ systems. A metabotoxin is an endogenously produced metabolite that causes adverse health effects at chronically high levels. Saccharopine is an organic acid. Abnormally high levels of organic acids in the blood (organic acidemia), urine (organic aciduria), the brain, and other tissues lead to general metabolic acidosis. Acidosis typically occurs when arterial pH falls below 7.35. In infants with acidosis, the initial symptoms include poor feeding, vomiting, loss of appetite, weak muscle tone (hypotonia), and lack of energy (lethargy). Many affected children with organic acidemias experience intellectual disability or delayed development.
Structure
Thumb
Synonyms
ValueSource
epsilon-N-(L-Glutar-2-yl)-L-lysineChEBI
N-[(S)-5-amino-5-Carboxypentyl]-L-glutamic acidChEBI
N6-(L-1,3-Dicarboxypropyl)-L-lysineChEBI
N-[(S)-5-amino-5-Carboxypentyl]-L-glutamateGenerator
(S)-N-(5-amino-5-Carboxypentyl)-L-glutamic acidHMDB
L-N-(5-amino-5-Carboxypentyl)-glutamic acidHMDB
L-SaccharopinHMDB
L-SaccharopineHMDB
N(6)-(L-1,3-Dicarboxypropyl)-L-lysineHMDB
N-(5-amino-5-Carboxypentyl)-glutamic acidHMDB
N-(5-amino-5-Carboxypentyl)-L-glutamic acidHMDB
N-[(5S)-5-amino-5-Carboxypentyl]-L-glutamic acidHMDB
SaccharopinHMDB
Chemical FormulaC11H20N2O6
Average Molecular Weight276.2863
Monoisotopic Molecular Weight276.132136382
IUPAC Name(2S)-2-{[(5S)-5-amino-5-carboxypentyl]amino}pentanedioic acid
Traditional Namesaccharopine
CAS Registry Number997-68-2
SMILES
N[C@@H](CCCCN[C@@H](CCC(O)=O)C(O)=O)C(O)=O
InChI Identifier
InChI=1S/C11H20N2O6/c12-7(10(16)17)3-1-2-6-13-8(11(18)19)4-5-9(14)15/h7-8,13H,1-6,12H2,(H,14,15)(H,16,17)(H,18,19)/t7-,8-/m0/s1
InChI KeyZDGJAHTZVHVLOT-YUMQZZPRSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as glutamic acid and derivatives. These are compounds containing glutamic acid or a derivative thereof resulting from reaction of glutamic acid at the amino group or the carboxy group, or from the replacement of any hydrogen of glycine by a heteroatom.
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassCarboxylic acids and derivatives
Sub ClassAmino acids, peptides, and analogues
Direct ParentGlutamic acid and derivatives
Alternative Parents
Substituents
  • Glutamic acid or derivatives
  • Alpha-amino acid
  • L-alpha-amino acid
  • Tricarboxylic acid or derivatives
  • Amino fatty acid
  • Fatty acyl
  • Amino acid
  • Carboxylic acid
  • Secondary aliphatic amine
  • Secondary amine
  • Amine
  • Primary amine
  • Organooxygen compound
  • Organonitrogen compound
  • Primary aliphatic amine
  • Organic nitrogen compound
  • Carbonyl group
  • Organic oxygen compound
  • Organopnictogen compound
  • Organic oxide
  • Hydrocarbon derivative
  • Aliphatic acyclic compound
Molecular FrameworkAliphatic acyclic compounds
External Descriptors
Ontology
Disposition

Route of exposure:

Source:

Biological location:

Process

Naturally occurring process:

Role

Indirect biological role:

Industrial application:

Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point247 - 250 °CNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
LogPNot AvailableNot Available
Predicted Properties
PropertyValueSource
Water Solubility5.25 g/LALOGPS
logP-2.8ALOGPS
logP-5.4ChemAxon
logS-1.7ALOGPS
pKa (Strongest Acidic)1.44ChemAxon
pKa (Strongest Basic)10.89ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count8ChemAxon
Hydrogen Donor Count5ChemAxon
Polar Surface Area149.95 ŲChemAxon
Rotatable Bond Count11ChemAxon
Refractivity63.95 m³·mol⁻¹ChemAxon
Polarizability28.14 ųChemAxon
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) (Non-derivatized)splash10-0a4i-0923000000-1964addb7be546c2a45aView in MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (Non-derivatized)splash10-0a4j-0913000000-49fae417f545c42253ddView in MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-0a4i-0923000000-1964addb7be546c2a45aView in MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-0a4j-0913000000-49fae417f545c42253ddView in MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-001u-6950000000-fed481b3c49c1ab6ccd2View in MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (3 TMS) - 70eV, Positivesplash10-006x-9220800000-77f63e444994f915feaaView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF (UPLC Q-Tof Premier, Waters) , Positivesplash10-001i-9240000000-d841eea4ebc5da1106f7View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF (UPLC Q-Tof Premier, Waters) , Negativesplash10-0a4i-0290000000-c0b375ed0505ad2eab6cView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , negativesplash10-0a4i-0290000000-c0b375ed0505ad2eab6cView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-001i-9240000000-d841eea4ebc5da1106f7View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-06ur-0190000000-34536967c85ac70477b5View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-01qi-2790000000-ef0279e3d556894509f0View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0019-6900000000-76748510f1b49f459cafView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-004i-0190000000-417ff61b4b14d1bfe5fcView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-01u9-1490000000-b4e2c5921f08ff4ee977View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0kms-7920000000-32382165ff3ba15b14d6View in MoNA
1D NMR1H NMR SpectrumNot AvailableView in JSpectraViewer
2D NMR[1H,13C] 2D NMR SpectrumNot AvailableView in JSpectraViewer
Biological Properties
Cellular Locations
  • Mitochondria
Biospecimen Locations
  • Blood
  • Feces
  • Urine
Tissue LocationNot Available
Pathways
NameSMPDB/PathwhizKEGG
2-aminoadipic 2-oxoadipic aciduriaThumbThumb?image type=greyscaleThumb?image type=simpleNot Available
Glutaric Aciduria Type IThumbThumb?image type=greyscaleThumb?image type=simpleNot Available
Hyperlysinemia I, FamilialThumbThumb?image type=greyscaleThumb?image type=simpleNot Available
Hyperlysinemia II or SaccharopinuriaThumbThumb?image type=greyscaleThumb?image type=simpleNot Available
Lysine DegradationThumbThumb?image type=greyscaleThumb?image type=simpleMap00310
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodExpected but not Quantified Not AvailableNot Available
Normal
    details
    FecesDetected but not Quantified Not SpecifiedBoth
    Normal
    details
    FecesDetected but not Quantified Adult (>18 years old)Both
    Normal
    details
    FecesDetected but not Quantified Adult (>18 years old)Both
    Normal
    details
    UrineDetected but not Quantified Children (1-13 years old)FemaleNormal details
    Abnormal Concentrations
    BiospecimenStatusValueAgeSexConditionReferenceDetails
    FecesDetected but not Quantified Adult (>18 years old)Both
    Colorectal cancer
    details
    FecesDetected but not Quantified Adult (>18 years old)Both
    Colorectal cancer
    details
    Associated Disorders and Diseases
    Disease ReferencesNone
    Associated OMIM IDsNone
    DrugBank IDDB04207
    Phenol Explorer Compound IDNot Available
    FoodDB IDFDB000461
    KNApSAcK IDC00007227
    Chemspider ID141086
    KEGG Compound IDC00449
    BioCyc IDSACCHAROPINE
    BiGG ID1484994
    Wikipedia LinkSaccharopine
    METLIN ID383
    PubChem Compound160556
    PDB IDSHR
    ChEBI ID16927
    References
    Synthesis ReferenceBurkard, Ulrike; Walther, Ingrid; Effenberger, Franz. Amino acids. 6. Investigations on the synthesis of L-saccharopin. Liebigs Annalen der Chemie (1986), (6), 1030-43.
    Material Safety Data Sheet (MSDS)Download (PDF)
    General References
    1. IJlst L, de Kromme I, Oostheim W, Wanders RJ: Molecular cloning and expression of human L-pipecolate oxidase. Biochem Biophys Res Commun. 2000 Apr 21;270(3):1101-5. [PubMed:10772957 ]
    2. Krieger I, Bachmann C, Gronemeyer WH, Cejka J: Propionic acidemia and hyperlysinemia in a case with ornithine transcarbamylase (OTC) deficiency. J Clin Endocrinol Metab. 1976 Oct;43(4):796-802. [PubMed:977722 ]
    3. Cederbaum SD, Shaw KN, Dancis J, Hutzler J, Blaskovics JC: Hyperlysinemia with saccharopinuria due to combined lysine-ketoglutarate reductase and saccharopine dehydrogenase deficiencies presenting as cystinuria. J Pediatr. 1979 Aug;95(2):234-8. [PubMed:571908 ]
    4. Casey RE, Zaleski WA, Philp M, Mendelson IS, MacKenzie SL: Biochemical and clinical studies of a new case of alpha-aminoadipic aciduria. J Inherit Metab Dis. 1978;1(4):129-35. [PubMed:117247 ]
    5. Fellows FC, Carson NA: Enzyme studies in a patient with saccharopinuria: a defect of lysine metabolism. Pediatr Res. 1974 Jan;8(1):42-9. [PubMed:4809305 ]
    6. Dancis J, Hutzler J, Cox RP: Familial hyperlysinemia: enzyme studies, diagnostic methods, comments on terminology. Am J Hum Genet. 1979 May;31(3):290-9. [PubMed:463877 ]
    7. Papes F, Kemper EL, Cord-Neto G, Langone F, Arruda P: Lysine degradation through the saccharopine pathway in mammals: involvement of both bifunctional and monofunctional lysine-degrading enzymes in mouse. Biochem J. 1999 Dec 1;344 Pt 2:555-63. [PubMed:10567240 ]

    Enzymes

    General function:
    Involved in oxidoreductase activity
    Specific function:
    Bifunctional enzyme that catalyzes the first two steps in lysine degradation. The N-terminal and the C-terminal contain lysine-ketoglutarate reductase and saccharopine dehydrogenase activity, respectively.
    Gene Name:
    AASS
    Uniprot ID:
    Q9UDR5
    Molecular weight:
    102130.895
    Reactions
    Saccharopine + NADP + Water → L-Lysine + Oxoglutaric acid + NADPH + Hydrogen Iondetails
    Saccharopine + NAD + Water → L-Glutamic acid + (S)-2-amino-6-oxohexanoate + NADH + Hydrogen Iondetails
    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:17139284 ]
    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:17016423 ]
    3. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [PubMed:10592235 ]
    General function:
    Involved in catalytic activity
    Specific function:
    N(6)-(L-1,3-dicarboxypropyl)-L-lysine + NAD(+) + H(2)O = L-glutamate + 2-aminoadipate 6-semialdehyde + NADH
    Gene Name:
    SCCPDH
    Uniprot ID:
    Q8NBX0
    Molecular weight:
    47151.0
    General function:
    Involved in oxidoreductase activity
    Specific function:
    Not Available
    Gene Name:
    AASS
    Uniprot ID:
    A4D0W4
    Molecular weight:
    102130.9