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Record Information
Version3.6
Creation Date2005-11-16 15:48:42 UTC
Update Date2013-05-29 19:25:20 UTC
HMDB IDHMDB00279
Secondary Accession NumbersNone
Metabolite Identification
Common NameSaccharopine
DescriptionSaccharopine is an intermediate in the degradation of lysine, formed by condensation of lysine and alpha-ketoglutarate. The saccharopine pathway is the main route for lysine degradation in mammal 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 (EC EC 1.5.1.8, LOR/SDH). The reactions involved by saccharopine dehydrogenases have a 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 the question of whether the degradation of lysine has any functional significance during brain development and puts 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 autosomic genetic disorder known as familial hyperlysinemia, which is characterized by serious defects in the functioning of the nervous system, and characterized by 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 ).
Structure
Thumb
Synonyms
  1. (S)-N-(5-amino-5-carboxypentyl)-L-Glutamic acid
  2. epsilon-N-(L-Glutar-2-yl)-L-lysine
  3. L-N-(5-Amino-5-carboxypentyl)-Glutamic acid
  4. L-Saccharopin
  5. L-Saccharopine
  6. N(6)-(L-1,3-Dicarboxypropyl)-L-lysine
  7. N-(5-Amino-5-carboxypentyl)-glutamic acid
  8. N-(5-Amino-5-carboxypentyl)-L-glutamic acid
  9. N-[(5S)-5-Amino-5-carboxypentyl]-L-Glutamic acid
  10. N6-(L-1,3-Dicarboxypropyl)-L-lysine
  11. Saccharopin
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
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
  • Organic Compounds
Substituents
  • Carboxylic Acid
  • Polyamine
  • Primary Aliphatic Amine (Alkylamine)
  • Secondary Aliphatic Amine (Dialkylamine)
  • Tricarboxylic Acid Derivative
Direct ParentAlpha Amino Acids and Derivatives
Ontology
StatusDetected and Not Quantified
Origin
  • Endogenous
Biofunction
  • Protein synthesis, amino acid biosynthesis
ApplicationNot Available
Cellular locations
  • Mitochondria
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 Area149.95ChemAxon
Rotatable Bond Count11ChemAxon
Refractivity63.95ChemAxon
Polarizability27.98ChemAxon
Spectra
SpectraGC-MSLC-MS1D NMR2D NMR
Biological Properties
Cellular Locations
  • Mitochondria
Biofluid Locations
  • Blood
  • Urine
Tissue LocationNot Available
Pathways
NameSMPDB LinkKEGG Link
Lysine DegradationSMP00037map00310
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodExpected but not QuantifiedNot ApplicableNot AvailableNot Available
Normal
  • Not Applicable
details
UrineDetected but not QuantifiedNot ApplicableChildren (1-13 years old)FemaleNormal details
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB04207
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDFDB000461
KNApSAcK IDC00007227
Chemspider ID141086
KEGG Compound IDC00449
BioCyc IDSACCHAROPINE
BiGG ID1484994
Wikipedia LinkSaccharopine
NuGOwiki LinkHMDB00279
Metagene LinkHMDB00279
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