MiMeDB: Showing metabocard for Saccharopine (MMDBc0000510)

Record Information

Version

1.0

Status

Detected and Quantified

Creation Date

2020-12-10 18:39:24 UTC

Update Date

2024-10-11 04:21:05 UTC

Metabolite ID

MMDBc0000510

Metabolite Identification

Common Name

Saccharopine

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.

Structure

MOL SDF PDB SMILES InChI

Synonyms

Not Available

Molecular Formula

C₁₁H₂₀N₂O₆

Average Mass

276.2863

Monoisotopic Mass

276.132136382

IUPAC Name

Not Available

Traditional Name

Not Available

CAS Registry Number

Not Available

SMILES

Not Available

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

ZDGJAHTZVHVLOT-YUMQZZPRSA-N

Chemical Taxonomy

Functional Ontology

Not Available

Physical Properties

State

Expected Solid

Predicted Properties

Not Available

Spectra

Not Available

Biological Properties

Cellular Locations

Mitochondria

Biospecimen Locations

Blood
Feces
Placenta
Urine

Tissue Locations

Placenta

Associated OMIM IDs

114500 (Colorectal cancer)
610247 (Eosinophilic esophagitis)

Human Proteins and Enzymes

Protein ID	Protein Name	Protein Type	Uniprot ID	Species
MMDBp0192472	Alpha-aminoadipic semialdehyde synthase, mitochondrial	Unknown	Q9UDR5	Homo sapiens
MMDBp0194066	Probable saccharopine dehydrogenase	Unknown	Q8NBX0	Homo sapiens
MMDBp0194178	Aminoadipate-semialdehyde synthase	Enzyme	A4D0W4	Homo sapiens

Human Pathways

Pathways

Name	SMPDB/PathBank

Metabolic Reactions

Reactions

Reaction ID	Precursor	Product	Enzyme	Data Source	Reference
MMDBr0002084	Oxoglutaric acid	Saccharopine	aminoadipate-semialdehyde synthase	VMH; KEGG	30371894
MMDBr0002085	Saccharopine	L-Glutamic acid	aminoadipate-semialdehyde synthase	VMH; KEGG	30371894
MMDBr0002583	Saccharopine	L-Glutamic acid	aminoadipate-semialdehyde synthase	VMH; KEGG	30371894
MMDBr0010977	Saccharopine	L-Glutamic acid	Not Available	VMH	30371894
MMDBr0010992	Saccharopine	Oxoglutaric acid	Not Available	VMH	30371894

Health Effects and Bioactivity

Health Outcome/Bioactivity	Metabolite Response/Effect	Evidence Type	Host and Biospecimen	Data Source	Reference

Microbial Sources

Superkingdom/Kingdom	Phylum	Total species	Hosts and Body Sites	Microbial Links
Bacteria/Eubacteria	Verrucomicrobia	1	Human feces; Human stool; Human ; Human urine	Indirect association between microbiota composition and metabolites measured in host biospecimen
Bacteria/Eubacteria	Firmicutes	11	Human stool; Human feces; Human ; Human urine; Human sputum	Indirect association between microbiota composition and metabolites measured in host biospecimen; Metabolic reconstruction
Archaea	Euryarchaeota	1	Human feces	Indirect association between microbiota composition and metabolites measured in host biospecimen
Archaea	Euryarchaeota	2	Human feces; Human	Indirect association between microbiota composition and metabolites measured in host biospecimen; Metabolic reconstruction
Bacteria/Eubacteria	Proteobacteria	12	Human feces; Human pleural fluid plaque; Human	Metabolic reconstruction
Bacteria	Actinobacteria	1	Human feces; Human	Metabolic reconstruction
Bacteria/Eubacteria	Actinobacteria	3	Human feces; Human	Metabolic reconstruction
Bacteria/Eubacteria	Planctomycetes	1	Human feces	Metabolic reconstruction
Eukaryota/Fungi	Ascomycota	10	Human feces; Human saliva	Unknown

Exposure Sources

Source Type	Activity	Data Source	Reference
Drugs	Antimicrobial	U.S. Environmental Protection Agency	CompTox
Cosmetics	Not Available	U.S. Environmental Protection Agency	CompTox
Domestics	Not Available	U.S. Environmental Protection Agency	CompTox

Host Biospecimen and Location

Host and Biospecimen	Status	Age	Sex	Health Condition	Data Source	Reference
Human Feces	Detected but not Quantified				HMDB
Human Placenta	Detected but not Quantified	Not Specified	Not Specified	Normal	HMDB	34986597
Human Urine	Detected but not Quantified	Children (1-13 years old)	Female	Normal	HMDB	117247
Human Feces	Detected but not Quantified	Not Specified	Both	Normal	HMDB	25486321
Human Feces	Detected but not Quantified	Adult (>18 years old)	Both	Normal	HMDB	27543620
Human Feces	Detected but not Quantified	Adult (>18 years old)	Both	Normal	HMDB	25037050
Human Feces	Detected but not Quantified	Adult (>18 years old)	Both	Normal	HMDB	29808030
Human Blood	Detected but not Quantified				HMDB

External Links

HMDB ID

Not Available

DrugBank ID

Not Available

Phenol Explorer Compound ID

Not Available

FooDB ID

Not Available

KNApSAcK ID

Not Available

Chemspider ID

Not Available

KEGG Compound ID

Not Available

BioCyc ID

Not Available

BiGG ID

Not Available

Wikipedia Link

Not Available

METLIN ID

Not Available

PubChem Compound

Not Available

PDB ID

Not Available

ChEBI ID

Not Available

Food Biomarker Ontology

Not Available

References

Synthesis Reference

Not Available

General References

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. doi: 10.1007/BF01805581. [PubMed:117247 ]
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 ]
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. doi: 10.1016/s0022-3476(79)80657-5. [PubMed:571908 ]
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. doi: 10.1210/jcem-43-4-796. [PubMed:977722 ]
Fellows FC, Carson NA: Enzyme studies in a patient with saccharopinuria: a defect of lysine metabolism. Pediatr Res. 1974 Jan;8(1):42-9. doi: 10.1203/00006450-197401000-00008. [PubMed:4809305 ]
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 ]
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. doi: 10.1006/bbrc.2000.2575. [PubMed:10772957 ]
Elshenawy S, Pinney SE, Stuart T, Doulias PT, Zura G, Parry S, Elovitz MA, Bennett MJ, Bansal A, Strauss JF 3rd, Ischiropoulos H, Simmons RA: The Metabolomic Signature of the Placenta in Spontaneous Preterm Birth. Int J Mol Sci. 2020 Feb 4;21(3). pii: ijms21031043. doi: 10.3390/ijms21031043. [PubMed:32033212 ]

Showing metabocard for Saccharopine (MMDBc0000510)

MOL for #<Metabolite:0x00007f3ddf403278>

3D MOL for #<Metabolite:0x00007f3ddf403278>

3D SDF for #<Metabolite:0x00007f3ddf403278>

3D-SDF for #<Metabolite:0x00007f3ddf403278>

PDB for #<Metabolite:0x00007f3ddf403278>

3D PDB for #<Metabolite:0x00007f3ddf403278>

SMILES for #<Metabolite:0x00007f3ddf403278>

INCHI for #<Metabolite:0x00007f3ddf403278>

Structure for #<Metabolite:0x00007f3ddf403278>

3D Structure for #<Metabolite:0x00007f3ddf403278>