T3DB: Saccharopine

Identification Taxonomy Biological Properties Physical Properties Toxicity Profile Spectra Concentrations Links References Gene Regulation Targets (1)XML

Targets (1)

Record Information

Version

2.0

Creation Date

2014-08-29 06:50:55 UTC

Update Date

2018-03-21 17:46:23 UTC

Accession Number

T3D4398

Identification

Common Name

Saccharopine

Class

Small Molecule

Description

Saccharopine 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.

Compound Type

Amine
Animal Toxin
Food Toxin
Mammal Toxin
Metabolite
Natural Compound
Organic Compound

Chemical Structure

MOL SDF PDB SMILES InChI

Synonyms

Synonym
(S)-N-(5-amino-5-carboxypentyl)-L-Glutamic acid
epsilon-N-(L-Glutar-2-yl)-L-lysine
L-N-(5-Amino-5-carboxypentyl)-Glutamic acid
L-Saccharopin
L-Saccharopine
N(6)-(L-1,3-Dicarboxypropyl)-L-lysine
N-(5-Amino-5-carboxypentyl)-glutamic acid
N-(5-Amino-5-carboxypentyl)-L-glutamic acid
N-[(5S)-5-Amino-5-carboxypentyl]-L-Glutamic acid
N6-(L-1,3-Dicarboxypropyl)-L-lysine
Saccharopin

Chemical Formula

C₁₁H₂₀N₂O₆

Average Molecular Mass

276.286 g/mol

Monoisotopic Mass

276.132 g/mol

CAS Registry Number

997-68-2

IUPAC Name

(2S)-2-{[(5S)-5-amino-5-carboxypentyl]amino}pentanedioic acid

Traditional Name

saccharopine

SMILES

[H][C@](N)(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 Key

InChIKey=ZDGJAHTZVHVLOT-YUMQZZPRSA-N

Chemical Taxonomy

Description

belongs to the class of organic compounds known as glutamic acid and derivatives. Glutamic acid and derivatives 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.

Kingdom

Organic compounds

Super Class

Organic acids and derivatives

Class

Carboxylic acids and derivatives

Sub Class

Amino acids, peptides, and analogues

Direct Parent

Glutamic 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 Framework

Aliphatic acyclic compounds

External Descriptors

L-lysine derivative (CHEBI:16927 )
amino acid opine (CHEBI:16927 )

Biological Properties

Status

Detected and Not Quantified

Origin

Endogenous

Cellular Locations

Membrane
Mitochondria

Biofluid Locations

Not Available

Tissue Locations

Not Available

Pathways

Name	SMPDB Link	KEGG Link
Lysine Degradation	SMP00037	map00310
Hyperlysinemia I, Familial	SMP00527	Not Available
Hyperlysinemia II or Saccharopinuria	SMP00528	Not Available
Saccharopinuria/Hyperlysinemia II	SMP00239	Not Available

Applications

Not Available

Biological Roles

Chemical Roles

Not Available

Physical Properties

State

Solid

Appearance

White powder.

Experimental Properties

Property	Value
Melting Point	247 - 250°C
Boiling Point	Not Available
Solubility	Not Available
LogP	Not Available

Predicted Properties

Property	Value	Source
Water Solubility	5.25 g/L	ALOGPS
logP	-2.8	ALOGPS
logP	-5.4	ChemAxon
logS	-1.7	ALOGPS
pKa (Strongest Acidic)	1.44	ChemAxon
pKa (Strongest Basic)	10.89	ChemAxon
Physiological Charge	-1	ChemAxon
Hydrogen Acceptor Count	8	ChemAxon
Hydrogen Donor Count	5	ChemAxon
Polar Surface Area	149.95 Å²	ChemAxon
Rotatable Bond Count	11	ChemAxon
Refractivity	63.95 m³·mol⁻¹	ChemAxon
Polarizability	28.14 Å³	ChemAxon
Number of Rings	0	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	Yes	ChemAxon
MDDR-like Rule	Yes	ChemAxon

Spectra

Spectrum Type	Description	Splash Key	Deposition Date	View
GC-MS	GC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (Non-derivatized)	splash10-0a4i-0923000000-1964addb7be546c2a45a	2014-06-16	View Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (Non-derivatized)	splash10-0a4j-0913000000-49fae417f545c42253dd	2014-06-16	View Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Non-derivatized)	splash10-0a4i-0923000000-1964addb7be546c2a45a	2017-09-12	View Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Non-derivatized)	splash10-0a4j-0913000000-49fae417f545c42253dd	2017-09-12	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	splash10-001u-6950000000-fed481b3c49c1ab6ccd2	2016-09-22	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (3 TMS) - 70eV, Positive	splash10-006x-9220800000-77f63e444994f915feaa	2017-10-06	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	Not Available	2021-10-12	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_1_1) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_1_2) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_1_3) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_1_4) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_1_5) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_2_1) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_2_2) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_2_3) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_2_4) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_2_5) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_2_6) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_2_7) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_2_8) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_2_9) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_2_10) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_2_11) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_3_2) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_3_3) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QTOF (UPLC Q-Tof Premier, Waters) , Positive	splash10-001i-9240000000-d841eea4ebc5da1106f7	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QTOF (UPLC Q-Tof Premier, Waters) , Negative	splash10-0a4i-0290000000-c0b375ed0505ad2eab6c	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QTOF , negative	splash10-0a4i-0290000000-c0b375ed0505ad2eab6c	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QTOF , positive	splash10-001i-9240000000-d841eea4ebc5da1106f7	2017-09-14	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-06ur-0190000000-34536967c85ac70477b5	2016-09-12	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-01qi-2790000000-ef0279e3d556894509f0	2016-09-12	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-0019-6900000000-76748510f1b49f459caf	2016-09-12	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-004i-0190000000-417ff61b4b14d1bfe5fc	2016-09-12	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-01u9-1490000000-b4e2c5921f08ff4ee977	2016-09-12	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-0kms-7920000000-32382165ff3ba15b14d6	2016-09-12	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-0059-0190000000-b1accd72c8a2f16e7a71	2021-09-22	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-001i-9310000000-56c681de611fbd62d1c7	2021-09-22	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-001i-9000000000-f91927cbf4969536ddce	2021-09-22	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-0a4i-0090000000-dfdb3652043e0e0c5f80	2021-09-22	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-057i-1390000000-910bea675f309038db9a	2021-09-22	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-0f95-7900000000-1df925bebb97a29a8080	2021-09-22	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 500 MHz, H₂O, experimental)	Not Available	2012-12-04	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 100 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 100 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 1000 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 1000 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 200 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 200 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 300 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 300 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 400 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 400 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 500 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 500 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 600 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 600 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 700 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 700 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 800 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 800 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 900 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 900 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
2D NMR	[¹H, ¹³C]-HSQC NMR Spectrum (2D, 600 MHz, H₂O, experimental)	Not Available	2012-12-05	View Spectrum

Toxicity Profile

Route of Exposure

Not Available

Mechanism of Toxicity

Not Available

Metabolism

Not Available

Toxicity Values

Not Available

Lethal Dose

Not Available

Carcinogenicity (IARC Classification)

No indication of carcinogenicity to humans (not listed by IARC).

Uses/Sources

This is an endogenously produced metabolite found in the human body. It is used in metabolic reactions, catabolic reactions or waste generation.

Minimum Risk Level

Not Available

Health Effects

Not Available

Symptoms

Not Available

Treatment

Not Available

Normal Concentrations

Not Available

Abnormal Concentrations

Not Available

External Links

DrugBank ID

DB04207

HMDB ID

HMDB00279

PubChem Compound ID

160556

ChEMBL ID

Not Available

ChemSpider ID

141086

KEGG ID

C00449

UniProt ID

Not Available

OMIM ID

ChEBI ID

16927

BioCyc ID

SACCHAROPINE

CTD ID

Not Available

Stitch ID

Not Available

PDB ID

SHR

ACToR ID

Not Available

Wikipedia Link

Saccharopine

References

Synthesis Reference

Not Available

MSDS

Link

General References

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. [463877 ]
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. [10567240 ]
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. [10772957 ]
Fellows FC, Carson NA: Enzyme studies in a patient with saccharopinuria: a defect of lysine metabolism. Pediatr Res. 1974 Jan;8(1):42-9. [4809305 ]
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. [977722 ]
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. [571908 ]
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. [117247 ]

Gene Regulation

Up-Regulated Genes

Not Available

Down-Regulated Genes

Not Available

Targets

Target Details

1. Alpha-aminoadipic semialdehyde synthase, mitochondrial

General Function:: Saccharopine dehydrogenase (nadp+, l-lysine-forming) 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 Da

References

Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
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. [17016423 ]
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. [10592235 ]

Saccharopine (T3D4398)

Structure for T3D4398: Saccharopine

Targets

References