创建日期
2005-11-16 15:48:42 UTC
更新日期
2021-09-14 15:41:42 UTC
二级访问
HMDB00279
HMDB0062698
HMDB62698
描述
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.
同义词
1:epsilon-N-(L-Glutar-2-yl)-L-lysine
2:N-[(S)-5-Amino-5-carboxypentyl]-L-glutamic acid
3:N6-(L-1,3-Dicarboxypropyl)-L-lysine
4:L-Saccharopine
5:N-[(S)-5-Amino-5-carboxypentyl]-L-glutamate
6:(S)-N-(5-Amino-5-carboxypentyl)-L-glutamic acid
7:L-N-(5-Amino-5-carboxypentyl)-glutamic acid
8:L-Saccharopin
9:N(6)-(L-1,3-Dicarboxypropyl)-L-lysine
10:N-(5-Amino-5-carboxypentyl)-glutamic acid
11:N-(5-Amino-5-carboxypentyl)-L-glutamic acid
12:N-[(5S)-5-Amino-5-carboxypentyl]-L-glutamic acid
13:Saccharopin
化学名称
(2S)-2-{[(5S)-5-amino-5-carboxypentyl]amino}pentanedioic acid
代谢物结构字符串
N[C@@H](CCCCN[C@@H](CCC(O)=O)C(O)=O)C(O)=O
inchi标识符
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
印记键
ZDGJAHTZVHVLOT-YUMQZZPRSA-N
分类学
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.
description:Glutamic acid and derivatives
kingdom:Organic compounds
super_class:Organic acids and derivatives
class:Carboxylic acids and derivatives
sub_class:Amino acids, peptides, and analogues
molecular_framework:Aliphatic acyclic compounds
1:Amino acids
2:Amino fatty acids
3:Carbonyl compounds
4:Carboxylic acids
5:Dialkylamines
6:Hydrocarbon derivatives
7:L-alpha-amino acids
8:Monoalkylamines
9:Organic oxides
10:Organopnictogen compounds
11:Tricarboxylic acids and derivatives
12:Aliphatic acyclic compound
13:Alpha-amino acid
14:Amine
15:Amino acid
16:Amino fatty acid
17:Carbonyl group
18:Carboxylic acid
19:Fatty acyl
20:Glutamic acid or derivatives
21:Hydrocarbon derivative
22:L-alpha-amino acid
23:Organic nitrogen compound
24:Organic oxide
25:Organic oxygen compound
26:Organonitrogen compound
27:Organooxygen compound
28:Organopnictogen compound
29:Primary aliphatic amine
30:Primary amine
31:Secondary aliphatic amine
32:Secondary amine
33:Tricarboxylic acid or derivatives
34:L-lysine derivative
35:amino acid opine
本体论
term:Disposition
definition:A concept that describes the origin of a chemical, its location within an organism, or its route of exposure.
parent_id:
level:1
type:parent
term:Route of exposure
definition:A mean by which a chemical agent comes in contact with an organism, either under intended or unintended circumstances.
parent_id:7724
*level:2
type:parent
term:Enteral
definition:Chemical exposure via the alimentary canal (mouth to anus).
parent_id:7743
**level:3
type:parent
term:Ingestion
definition:Chemical exposure facilitated by entry through the mouth.
parent_id:7744
***level:4
type:child
synonym:Digestion
term:Source
definition:Natural or synthetic origin of a chemical.
parent_id:7724
*level:2
type:parent
term:Endogenous
definition:
parent_id:7735
**level:3
type:child
term:Food
definition:
parent_id:7735
**level:3
type:child
term:Biological
definition:A living organism (species or a higher taxonomy rank), in which a chemical can be found.
parent_id:7735
**level:3
type:parent
term:Animal
definition:A living organism belonging to the kingdom animalia. it feeds on organic matter, typically having specialized sense organs and nervous system and able to respond rapidly to stimuli.
parent_id:7736
***level:4
type:child
synonym:Fauna
term:Plant
definition:A living organism belonging to the kingdom plantea. typically, it grows in a permanent site, absorbs water and inorganic substances through its roots, and synthesizes nutrients in its leaves by photosynthesis using the green pigment chlorophyll. examples incude trees, shrubs, herbs, grasses, ferns, and mosses.
parent_id:7736
***level:4
type:parent
synonym:Flora
term:Biological location
definition:The physiological origin within an organism, including anatomical compnents, biofluids and excreta.
parent_id:7724
*level:2
type:parent
term:Tissue and substructures
definition:An anatomical organizational level including multiple cells yet not comprising a complete organ .
parent_id:7725
**level:3
type:parent
term:Placenta
definition:An organ present in some vertebrates during embryonic gestation that surrounds the fetus and provides it with nutrients and oxygen, facilitates gas and waste exchange between the fetus and mother, and provides parasitic cloaking from the mother's immune system by excretion of neurokinin b. (nci).
parent_id:7729
***level:4
type:child
term:Biofluid and excreta
definition:A liquid, semi-solid or solid material originating in the body.
parent_id:7725
**level:3
type:parent
term:Feces
definition:The material discharged from the bowel during defecation. It consists of undigested food, intestinal mucus, epithelial cells, and bacteria.
parent_id:7731
***level:4
type:child
synonym:Fecal
synonym:Stool
synonym:Faecal
synonym:Faeces
term:Urine
definition:Excretion in liquid state processed by the kidney.
parent_id:7731
***level:4
type:child
term:Blood
definition:A liquid tissue with the primary function of transporting oxygen and carbon dioxide (nci). it supplies the tissues with nutrients, removes waste products, and contains various components of the immune system defending the body against infection.
parent_id:7731
***level:4
type:child
term:Subcellular
definition:An anatomical organizational level including a component within a biological cell .
parent_id:7725
**level:3
type:parent
term:Mitochondria
definition:
parent_id:7730
***level:4
type:child
term:Cytoplasm
definition:The portion of the cell contained within the plasma membrane but excluding the nucleus.
parent_id:7730
***level:4
type:child
synonym:Cytoplasma
term:Process
definition:Biological or chemical events, or a series thereof, leading to a known function or end-product.
parent_id:
level:1
type:parent
term:Naturally occurring process
definition:Naturally-occurring molecular events or a series thereof, leading to a known function or end-product.
parent_id:7659
*level:2
type:parent
term:Biological process
definition:Biological or chemical events or a series thereof, leading to a known function or end-product within an organism.
parent_id:7660
**level:3
type:parent
term:Biochemical pathway
definition:A linked series of chemical reactions that occur in a defined order within or between organism cells, and lead to a known function or end product.
parent_id:7661
***level:4
type:parent
term:Role
definition:The purpose or function assumed by a chemical, either naturally or as intended by humans .
parent_id:
level:1
type:parent
term:Indirect biological role
definition:An indirect function of a chemical which affect the physiological state of any organism (apart from the source organism, if of biological source).
parent_id:7671
*level:2
type:parent
term:Metabotoxin
definition:An endogenous metabolite that causes adverse health effects at chronically high levels.
parent_id:7691
**level:3
type:child
term:Acidogen
definition:An acidic chemical substance that induces acidosis, which has multiple adverse effects on many organ systems.
parent_id:7691
**level:3
type:child
term:Industrial application
definition:The assumed function of a chemical utilized by human.
parent_id:7671
*level:2
type:parent
term:Pharmaceutical industry
definition:A pharmacologic activity for which a chemical substance is utilized owing to its biological role.
parent_id:7678
**level:3
type:parent
term:Pharmaceutical
definition:
parent_id:7679
***level:4
type:child
实验性质
1:
kind:melting_point
value:247 - 250 °C
source:
预测性质
1:
kind:logp
value:-2.77
source:ALOGPS
2:
kind:logs
value:-1.72
source:ALOGPS
3:
kind:solubility
value:5.25 g/L
source:ALOGPS
4:
kind:logp
value:-5.4
source:ChemAxon
5:
kind:pka_strongest_acidic
value:1.44
source:ChemAxon
6:
kind:pka_strongest_basic
value:10.89
source:ChemAxon
7:
kind:iupac
value:(2S)-2-{[(5S)-5-amino-5-carboxypentyl]amino}pentanedioic acid
source:ChemAxon
8:
kind:average_mass
value:276.2863
source:ChemAxon
9:
kind:mono_mass
value:276.132136382
source:ChemAxon
10:
kind:smiles
value:N[C@@H](CCCCN[C@@H](CCC(O)=O)C(O)=O)C(O)=O
source:ChemAxon
11:
kind:formula
value:C11H20N2O6
source:ChemAxon
12:
kind:inchi
value: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
source:ChemAxon
13:
kind:inchikey
value:ZDGJAHTZVHVLOT-YUMQZZPRSA-N
source:ChemAxon
14:
kind:polar_surface_area
value:149.95
source:ChemAxon
15:
kind:refractivity
value:63.95
source:ChemAxon
16:
kind:polarizability
value:28.14
source:ChemAxon
17:
kind:rotatable_bond_count
value:11
source:ChemAxon
18:
kind:acceptor_count
value:8
source:ChemAxon
19:
kind:donor_count
value:5
source:ChemAxon
20:
kind:physiological_charge
value:-1
source:ChemAxon
21:
kind:formal_charge
value:0
source:ChemAxon
22:
kind:number_of_rings
value:0
source:ChemAxon
23:
kind:bioavailability
value:Yes
source:ChemAxon
24:
kind:rule_of_five
value:Yes
source:ChemAxon
25:
kind:ghose_filter
value:No
source:ChemAxon
26:
kind:veber_rule
value:No
source:ChemAxon
27:
kind:mddr_like_rule
value:No
source:ChemAxon
生物学性质
1:
cellular:(1):Mitochondria
2:
biospecimen:(1):Blood
biospecimen:(2):Feces
biospecimen:(3):Urine
3:
tissue:(1):Placenta
4:
[1]:
name:2-aminoadipic 2-oxoadipic aciduria
smpdb_id:SMP00719
kegg_map_id:
[2]:
name:Glutaric Aciduria Type I
smpdb_id:SMP00186
kegg_map_id:
[3]:
name:Hyperlysinemia I, Familial
smpdb_id:SMP00527
kegg_map_id:
[4]:
name:Hyperlysinemia II or Saccharopinuria
smpdb_id:SMP00528
kegg_map_id:
[5]:
name:Lysine degradation
smpdb_id:
kegg_map_id:map00310
[6]:
name:Pyridoxine dependency with seizures
smpdb_id:SMP00571
kegg_map_id:
[7]:
name:Saccharopinuria/Hyperlysinemia II
smpdb_id:SMP00239
kegg_map_id:
正常浓度
1:
biospecimen:Blood
concentration_value:
concentration_units:
subject_age:
subject_sex:
subject_condition:Normal
2:
biospecimen:Feces
concentration_value:
concentration_units:
subject_age:Not Specified
subject_sex:Both
subject_condition:Normal
3:
biospecimen:Feces
concentration_value:
concentration_units:
subject_age:Adult (>18 years old)
subject_sex:Both
subject_condition:Normal
4:
biospecimen:Feces
concentration_value:
concentration_units:
subject_age:Adult (>18 years old)
subject_sex:Both
subject_condition:Normal
5:
biospecimen:Feces
concentration_value:
concentration_units:
subject_age:Adult (>18 years old)
subject_sex:Both
subject_condition:Normal
6:
biospecimen:Urine
concentration_value:
concentration_units:
subject_age:Children (1-13 years old)
subject_sex:Female
subject_condition:Normal
异常浓度
1:
biospecimen:Feces
concentration_value:
concentration_units:
patient_age:Adult (>18 years old)
patient_sex:Both
patient_information:Colorectal cancer
2:
biospecimen:Feces
concentration_value:
concentration_units:
patient_age:Adult (>18 years old)
patient_sex:Both
patient_information:Colorectal cancer
疾病参考
1:
name:Colorectal cancer
omim_id:114500
[1]:
reference_text:Ishiwata S, Itoh K, Yamaguchi T, Ishida N, Mizugaki M: Comparison of serum and urinary levels of modified nucleoside, 1-methyladenosine, in cancer patients using a monoclonal antibody-based inhibition ELISA. Tohoku J Exp Med. 1995 May;176(1):61-8.
pubmed_id:7482520
[2]:
reference_text:Cheng Y, Xie G, Chen T, Qiu Y, Zou X, Zheng M, Tan B, Feng B, Dong T, He P, Zhao L, Zhao A, Xu LX, Zhang Y, Jia W: Distinct urinary metabolic profile of human colorectal cancer. J Proteome Res. 2012 Feb 3;11(2):1354-63. doi: 10.1021/pr201001a. Epub 2011 Dec 28.
pubmed_id:22148915
[3]:
reference_text:Monleon D, Morales JM, Barrasa A, Lopez JA, Vazquez C, Celda B: Metabolite profiling of fecal water extracts from human colorectal cancer. NMR Biomed. 2009 Apr;22(3):342-8. doi: 10.1002/nbm.1345.
pubmed_id:19006102
[4]:
reference_text:Weir TL, Manter DK, Sheflin AM, Barnett BA, Heuberger AL, Ryan EP: Stool microbiome and metabolome differences between colorectal cancer patients and healthy adults. PLoS One. 2013 Aug 6;8(8):e70803. doi: 10.1371/journal.pone.0070803. Print 2013.
pubmed_id:23940645
[5]:
reference_text:Phua LC, Chue XP, Koh PK, Cheah PY, Ho HK, Chan EC: Non-invasive fecal metabonomic detection of colorectal cancer. Cancer Biol Ther. 2014 Apr;15(4):389-97. doi: 10.4161/cbt.27625. Epub 2014 Jan 14.
pubmed_id:24424155
[6]:
reference_text:Ritchie SA, Ahiahonu PW, Jayasinghe D, Heath D, Liu J, Lu Y, Jin W, Kavianpour A, Yamazaki Y, Khan AM, Hossain M, Su-Myat KK, Wood PL, Krenitsky K, Takemasa I, Miyake M, Sekimoto M, Monden M, Matsubara H, Nomura F, Goodenowe DB: Reduced levels of hydroxylated, polyunsaturated ultra long-chain fatty acids in the serum of colorectal cancer patients: implications for early screening and detection. BMC Med. 2010 Feb 15;8:13. doi: 10.1186/1741-7015-8-13.
pubmed_id:20156336
[7]:
reference_text:Qiu Y, Cai G, Su M, Chen T, Zheng X, Xu Y, Ni Y, Zhao A, Xu LX, Cai S, Jia W: Serum metabolite profiling of human colorectal cancer using GC-TOFMS and UPLC-QTOFMS. J Proteome Res. 2009 Oct;8(10):4844-50. doi: 10.1021/pr9004162.
pubmed_id:19678709
[8]:
reference_text:Ni Y, Xie G, Jia W: Metabonomics of human colorectal cancer: new approaches for early diagnosis and biomarker discovery. J Proteome Res. 2014 Sep 5;13(9):3857-70. doi: 10.1021/pr500443c. Epub 2014 Aug 14.
pubmed_id:25105552
[9]:
reference_text:Ikeda A, Nishiumi S, Shinohara M, Yoshie T, Hatano N, Okuno T, Bamba T, Fukusaki E, Takenawa T, Azuma T, Yoshida M: Serum metabolomics as a novel diagnostic approach for gastrointestinal cancer. Biomed Chromatogr. 2012 May;26(5):548-58. doi: 10.1002/bmc.1671. Epub 2011 Jul 20.
pubmed_id:21773981
[10]:
reference_text:Goedert JJ, Sampson JN, Moore SC, Xiao Q, Xiong X, Hayes RB, Ahn J, Shi J, Sinha R: Fecal metabolomics: assay performance and association with colorectal cancer. Carcinogenesis. 2014 Sep;35(9):2089-96. doi: 10.1093/carcin/bgu131. Epub 2014 Jul 18.
pubmed_id:25037050
[11]:
reference_text:Sinha R, Ahn J, Sampson JN, Shi J, Yu G, Xiong X, Hayes RB, Goedert JJ: Fecal Microbiota, Fecal Metabolome, and Colorectal Cancer Interrelations. PLoS One. 2016 Mar 25;11(3):e0152126. doi: 10.1371/journal.pone.0152126. eCollection 2016.
pubmed_id:27015276
[12]:
reference_text:Lin Y, Ma C, Liu C, Wang Z, Yang J, Liu X, Shen Z, Wu R: NMR-based fecal metabolomics fingerprinting as predictors of earlier diagnosis in patients with colorectal cancer. Oncotarget. 2016 May 17;7(20):29454-64. doi: 10.18632/oncotarget.8762.
pubmed_id:27107423
[13]:
reference_text:Brown DG, Rao S, Weir TL, O'Malia J, Bazan M, Brown RJ, Ryan EP: Metabolomics and metabolic pathway networks from human colorectal cancers, adjacent mucosa, and stool. Cancer Metab. 2016 Jun 6;4:11. doi: 10.1186/s40170-016-0151-y. eCollection 2016.
pubmed_id:27275383
[14]:
reference_text:Wang X, Wang J, Rao B, Deng L: Gut flora profiling and fecal metabolite composition of colorectal cancer patients and healthy individuals. Exp Ther Med. 2017 Jun;13(6):2848-2854. doi: 10.3892/etm.2017.4367. Epub 2017 Apr 20.
pubmed_id:28587349
[15]:
reference_text:Silke Matysik, Caroline Ivanne Le Roy, Gerhard Liebisch, Sandrine Paule Claus. Metabolomics of fecal samples: A practical consideration. Trends in Food Science & Technology. Vol. 57, Part B, Nov. 2016, p.244-255: http://www.sciencedirect.com/science/article/pii/S0924224416301984
综合参考
Burkard, Ulrike; Walther, Ingrid; Effenberger, Franz. Amino acids. 6. Investigations on the synthesis of L-saccharopin. Liebigs Annalen der Chemie (1986), (6), 1030-43.
一般参考
1:
protein_accession:HMDBP00852
name:Alpha-aminoadipic semialdehyde synthase, mitochondrial
uniprot_id:Q9UDR5
gene_name:AASS
protein_type:Unknown
2:
protein_accession:HMDBP07267
name:Probable saccharopine dehydrogenase
uniprot_id:Q8NBX0
gene_name:SCCPDH
protein_type:Unknown
3:
protein_accession:HMDBP07400
name:Aminoadipate-semialdehyde synthase
uniprot_id:A4D0W4
gene_name:AASS
protein_type:Enzyme
蛋白质结合
1:
reference_text: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_id:10772957
2:
reference_text: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_id:977722
3:
reference_text: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_id:571908
4:
reference_text: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_id:117247
5:
reference_text: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_id:4809305
6:
reference_text: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_id:463877
7:
reference_text: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_id:10567240
8:
reference_text: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_id:32033212