创建日期
2005-11-16 15:48:42 UTC
更新日期
2021-09-14 15:20:01 UTC
描述
Dihydrothymine (CAS: 696-04-8) is an intermediate breakdown product of thymine. Dihydropyrimidine dehydrogenase catalyzes the reduction of thymine into 5,6-dihydrothymine; then dihydropyrimidinase hydrolyzes 5,6-dihydrothymine into N-carbamyl-beta-alanine. Finally, beta-ureidopropionase catalyzes the conversion of N-carbamyl-beta-alanine into beta-alanine. When present at abnormally high levels, dihydrothymine can be toxic, although the mechanism of toxicity is not clear. In particular, patients with dihydropyrimidinase deficiency exhibit highly increased concentrations of 5,6-dihydrouracil and 5,6-dihydrothymine; and moderately increased concentrations of uracil and thymine can be detected in urine. Dihydropyrimidinase deficiency is a disorder that can cause neurological and gastrointestinal problems in some affected individuals. The most common neurological abnormalities that occur are intellectual disability, seizures, weak muscle tone (hypotonia), abnormally small head size (microcephaly), and autistic behaviours that affect communication and social interaction. Gastrointestinal problems that occur in dihydropyrimidinase deficiency include the backflow of acidic stomach contents into the esophagus (gastroesophageal reflux) and recurrent episodes of vomiting.
同义词
1:(-)-(S)-5,6-Dihydrothymine
2:(5S)-5-Methyl-1,3-diazinane-2,4-dione
3:5,6-Dihydro-5-methyluracil
4:5,6-Dihydrothymine
5:5-Methyl-5,6-dihydrouracil
6:5-Methyldihydropyrimidine-2,4(1H,3H)-dione
7:Dihydro-5-methyl-2,4(1H,3H)-pyrimidinedione
8:Dihydrothymine
化学名称
(5S)-5-methyl-1,3-diazinane-2,4-dione
传统名称
(5S)-5-methyl-1,3-diazinane-2,4-dione
代谢物结构字符串
C[C@H]1CNC(=O)NC1=O
inchi标识符
InChI=1S/C5H8N2O2/c1-3-2-6-5(9)7-4(3)8/h3H,2H2,1H3,(H2,6,7,8,9)/t3-/m0/s1
印记键
NBAKTGXDIBVZOO-VKHMYHEASA-N
分类学
description: belongs to the class of organic compounds known as pyrimidones. Pyrimidones are compounds that contain a pyrimidine ring, which bears a ketone. Pyrimidine is a 6-membered ring consisting of four carbon atoms and two nitrogen centers at the 1- and 3- ring positions.
description:Pyrimidones
kingdom:Organic compounds
super_class:Organoheterocyclic compounds
class:Diazines
sub_class:Pyrimidines and pyrimidine derivatives
molecular_framework:Aliphatic heteromonocyclic compounds
1:Azacyclic compounds
2:Carbonyl compounds
3:Diazinanes
4:Dicarboximides
5:Hydrocarbon derivatives
6:N-acyl ureas
7:Organic oxides
8:Organonitrogen compounds
9:Organopnictogen compounds
10:1,3-diazinane
11:Aliphatic heteromonocyclic compound
12:Azacycle
13:Carbonic acid derivative
14:Carbonyl group
15:Carboxylic acid derivative
16:Dicarboximide
17:Hydrocarbon derivative
18:N-acyl urea
19:Organic nitrogen compound
20:Organic oxide
21:Organic oxygen compound
22:Organonitrogen compound
23:Organooxygen compound
24:Organopnictogen compound
25:Pyrimidone
26:Urea
27:Ureide
本体论
term:Physiological effect
definition:The effect on an organism physiology, resulting from its exposure to a chemical.
parent_id:
level:1
type:parent
term:Health effect
definition:A health condition or observation associated with a stimuli or with a biological activity of a chemical.
parent_id:7693
*level:2
type:parent
term:Health condition
definition:A health effect that consists on short or long-term disease, condition, disorder, syndrome or constant abnormality.
parent_id:7694
**level:3
type:parent
term:Beta-ureidopropionase deficiency
definition:
parent_id:7695
***level:4
type:child
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:Organ and components
definition:An anatomical organizational level including multiple tissues or substructures, which enables a common biological function.
parent_id:7725
**level:3
type:parent
term:Prostate
definition:The male reproductive accessory gland that produces prostatic fluid and is located adjacent to or around the urethra distal to the urinary bladder in mammals. (nci).
parent_id:7727
***level:4
type:child
synonym:Prostate gland
term:Biofluid and excreta
definition:A liquid, semi-solid or solid material originating in the body.
parent_id:7725
**level:3
type:parent
term:Saliva
definition:The watery fluid in the mouth made by the salivary glands. saliva moistens food to help digestion and it helps protect the mouth against infections. (nci).
parent_id:7731
***level:4
type:child
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:Cerebrospinal fluid
definition:The fluid that is contained within the brain ventricles, the subarachnoid space and the central canal of the spinal cord. (nci).
parent_id:7731
***level:4
type:child
synonym:Csf
term:Subcellular
definition:An anatomical organizational level including a component within a biological cell .
parent_id:7725
**level:3
type:parent
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:Biological role
definition:The biological function of a chemical. the biological role answers the question how a chemical is involved in molecular processes in an organism. this can include biochemical effects of non-endogenous chemicals, which are also assigned an industrial application such as pharmaceuticals. the biological role is limited to cellular levls, and will not include role at system process level, such as a chemical which has a role in a disease.
parent_id:7671
*level:2
type:parent
term:Metabolite
definition:A chemical substance produced during metabolism process, as an intermediate or end-product.
parent_id:7672
**level:3
type:child
预测性质
1:
kind:logp
value:-0.80
source:ALOGPS
2:
kind:logs
value:-0.84
source:ALOGPS
3:
kind:solubility
value:18.7 g/L
source:ALOGPS
4:
kind:logp
value:-0.67
source:ChemAxon
5:
kind:pka_strongest_acidic
value:11.7
source:ChemAxon
6:
kind:pka_strongest_basic
value:-7.4
source:ChemAxon
7:
kind:iupac
value:(5S)-5-methyl-1,3-diazinane-2,4-dione
source:ChemAxon
8:
kind:average_mass
value:128.131
source:ChemAxon
9:
kind:mono_mass
value:128.058577506
source:ChemAxon
10:
kind:smiles
value:C[C@H]1CNC(=O)NC1=O
source:ChemAxon
11:
kind:formula
value:C5H8N2O2
source:ChemAxon
12:
kind:inchi
value:InChI=1S/C5H8N2O2/c1-3-2-6-5(9)7-4(3)8/h3H,2H2,1H3,(H2,6,7,8,9)/t3-/m0/s1
source:ChemAxon
13:
kind:inchikey
value:NBAKTGXDIBVZOO-VKHMYHEASA-N
source:ChemAxon
14:
kind:polar_surface_area
value:58.2
source:ChemAxon
15:
kind:refractivity
value:30.32
source:ChemAxon
16:
kind:polarizability
value:12.03
source:ChemAxon
17:
kind:rotatable_bond_count
value:0
source:ChemAxon
18:
kind:acceptor_count
value:2
source:ChemAxon
19:
kind:donor_count
value:2
source:ChemAxon
20:
kind:physiological_charge
value:0
source:ChemAxon
21:
kind:formal_charge
value:0
source:ChemAxon
22:
kind:number_of_rings
value:1
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):Cytoplasm
2:
biospecimen:(1):Blood
biospecimen:(2):Cerebrospinal Fluid (CSF)
biospecimen:(3):Feces
biospecimen:(4):Saliva
biospecimen:(5):Urine
3:
tissue:(1):Prostate
4:
[1]:
name:Beta Ureidopropionase Deficiency
smpdb_id:SMP00172
kegg_map_id:
[2]:
name:Dihydropyrimidinase Deficiency
smpdb_id:SMP00178
kegg_map_id:
[3]:
name:MNGIE (Mitochondrial Neurogastrointestinal Encephalopathy)
smpdb_id:SMP00202
kegg_map_id:
[4]:
name:Pyrimidine metabolism
smpdb_id:
kegg_map_id:map00240
[5]:
name:UMP Synthase Deficiency (Orotic Aciduria)
smpdb_id:SMP00219
kegg_map_id:
正常浓度
1:
biospecimen:Blood
concentration_value:
concentration_units:
subject_age:
subject_sex:
subject_condition:Normal
2:
biospecimen:Cerebrospinal Fluid (CSF)
concentration_value:1.1 +/- 0.3
concentration_units:uM
subject_age:Adult (>18 years old)
subject_sex:Not Specified
subject_condition:Normal
3:
biospecimen:Feces
concentration_value:
concentration_units:
subject_age:Adult (>18 years old)
subject_sex:Both
subject_condition:Normal
4:
biospecimen:Saliva
concentration_value:
concentration_units:
subject_age:Adult (>18 years old)
subject_sex:Male
subject_condition:Normal
5:
biospecimen:Saliva
concentration_value:
concentration_units:
subject_age:Adult (>18 years old)
subject_sex:Male
subject_condition:Normal
6:
biospecimen:Saliva
concentration_value:
concentration_units:
subject_age:Adult (>18 years old)
subject_sex:Male
subject_condition:Normal
7:
biospecimen:Saliva
concentration_value:
concentration_units:
subject_age:Adult (>18 years old)
subject_sex:Male
subject_condition:Normal
8:
biospecimen:Saliva
concentration_value:
concentration_units:
subject_age:Adult (>18 years old)
subject_sex:Male
subject_condition:Normal
9:
biospecimen:Saliva
concentration_value:
concentration_units:
subject_age:Adult (>18 years old)
subject_sex:Male
subject_condition:Normal
10:
biospecimen:Saliva
concentration_value:
concentration_units:
subject_age:Adult (>18 years old)
subject_sex:Male
subject_condition:Normal
11:
biospecimen:Saliva
concentration_value:
concentration_units:
subject_age:Adult (>18 years old)
subject_sex:Male
subject_condition:Normal
12:
biospecimen:Saliva
concentration_value:
concentration_units:
subject_age:Adult (>18 years old)
subject_sex:Male
subject_condition:Normal
13:
biospecimen:Saliva
concentration_value:
concentration_units:
subject_age:Adult (>18 years old)
subject_sex:Male
subject_condition:Normal
14:
biospecimen:Urine
concentration_value:0.4
concentration_units:umol/mmol creatinine
subject_age:Adult (>18 years old)
subject_sex:Both
subject_condition:Normal
15:
biospecimen:Urine
concentration_value:5.00 (0.00-10.00)
concentration_units:umol/mmol creatinine
subject_age:Adult (>18 years old)
subject_sex:Both
subject_condition:Normal
16:
biospecimen:Urine
concentration_value:0-3
concentration_units:umol/mmol creatinine
subject_age:Children (1 - 18 years old)
subject_sex:Both
subject_condition:Normal
17:
biospecimen:Urine
concentration_value:2.4 (1.3-4.4)
concentration_units:umol/mmol creatinine
subject_age:Adult (>18 years old)
subject_sex:Both
subject_condition:Normal
18:
biospecimen:Urine
concentration_value:8.736 +/- 1.827
concentration_units:umol/mmol creatinine
subject_age:Children (1 - 13 years old)
subject_sex:Not Specified
subject_condition:Normal
19:
biospecimen:Urine
concentration_value:0.40 (0.17-0.64)
concentration_units:umol/mmol creatinine
subject_age:Adult (>18 years old)
subject_sex:Male
subject_condition:Normal
20:
biospecimen:Urine
concentration_value:<0.6
concentration_units:umol/mmol creatinine
subject_age:Infant (0-1 year old)
subject_sex:Both
subject_condition:Normal
21:
biospecimen:Urine
concentration_value:0.57 (0.21-0.94)
concentration_units:umol/mmol creatinine
subject_age:Adult (>18 years old)
subject_sex:Female
subject_condition:Normal
异常浓度
1:
biospecimen:Cerebrospinal Fluid (CSF)
concentration_value:0.0 - 24.0
concentration_units:uM
patient_age:Not Specified
patient_sex:Both
patient_information:Dihydropyrimidinase deficiency
2:
biospecimen:Cerebrospinal Fluid (CSF)
concentration_value:4.0 - 5.2
concentration_units:uM
patient_age:Adult (>18 years old)
patient_sex:Not Specified
patient_information:Beta-ureidopropionase deficiency
3:
biospecimen:Urine
concentration_value:11.664 +/- 5.285
concentration_units:umol/mmol creatinine
patient_age:Children (1 - 13 years old)
patient_sex:Not Specified
patient_information:Eosinophilic esophagitis
疾病参考
1:
name:Dihydropyrimidinase deficiency
omim_id:222748
[1]:
reference_text:van Kuilenburg AB, Meijer J, Dobritzsch D, Meinsma R, Duran M, Lohkamp B, Zoetekouw L, Abeling NG, van Tinteren HL, Bosch AM: Clinical, biochemical and genetic findings in two siblings with a dihydropyrimidinase deficiency. Mol Genet Metab. 2007 Jun;91(2):157-64. Epub 2007 Mar 26.
pubmed_id:17383919
2:
name:Beta-ureidopropionase deficiency
omim_id:613161
[1]:
reference_text:van Kuilenburg AB, Meinsma R, Beke E, Assmann B, Ribes A, Lorente I, Busch R, Mayatepek E, Abeling NG, van Cruchten A, Stroomer AE, van Lenthe H, Zoetekouw L, Kulik W, Hoffmann GF, Voit T, Wevers RA, Rutsch F, van Gennip AH: beta-Ureidopropionase deficiency: an inborn error of pyrimidine degradation associated with neurological abnormalities. Hum Mol Genet. 2004 Nov 15;13(22):2793-801. Epub 2004 Sep 22.
pubmed_id:15385443
3:
name:Eosinophilic esophagitis
omim_id:610247
[1]:
reference_text:Mordechai, Hien, and David S. Wishart
pubmed_id:
代谢途径的数据库编号
DIHYDRO-THYMINE
综合参考
Yamane, Tetsuo; Wyluda, Benjamin J.; Shulman, Robert G. Dihydrothymine from ultraviolet-irradiated DNA. Proceedings of the National Academy of Sciences of the United States of America (1967), 58(2), 439-42.
一般参考
1:
protein_accession:HMDBP00543
name:Dihydropyrimidinase
uniprot_id:Q14117
gene_name:DPYS
protein_type:Unknown
2:
protein_accession:HMDBP00727
name:Dihydropyrimidine dehydrogenase [NADP(+)]
uniprot_id:Q12882
gene_name:DPYD
protein_type:Unknown
蛋白质结合
1:
reference_text:Sreekumar A, Poisson LM, Rajendiran TM, Khan AP, Cao Q, Yu J, Laxman B, Mehra R, Lonigro RJ, Li Y, Nyati MK, Ahsan A, Kalyana-Sundaram S, Han B, Cao X, Byun J, Omenn GS, Ghosh D, Pennathur S, Alexander DC, Berger A, Shuster JR, Wei JT, Varambally S, Beecher C, Chinnaiyan AM: Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression. Nature. 2009 Feb 12;457(7231):910-4. doi: 10.1038/nature07762.
pubmed_id:19212411
2:
reference_text:Hofmann U, Schwab M, Seefried S, Marx C, Zanger UM, Eichelbaum M, Murdter TE: Sensitive method for the quantification of urinary pyrimidine metabolites in healthy adults by gas chromatography-tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2003 Jul 5;791(1-2):371-80.
pubmed_id:12798197
3:
reference_text:Assmann B, Hoffmann GF, Wagner L, Brautigam C, Seyberth HW, Duran M, Van Kuilenburg AB, Wevers R, Van Gennip AH: Dihydropyrimidinase deficiency and congenital microvillous atrophy: coincidence or genetic relation? J Inherit Metab Dis. 1997 Sep;20(5):681-8.
pubmed_id:9323563
4:
reference_text:van Lenthe H, van Kuilenburg AB, Ito T, Bootsma AH, van Cruchten A, Wada Y, van Gennip AH: Defects in pyrimidine degradation identified by HPLC-electrospray tandem mass spectrometry of urine specimens or urine-soaked filter paper strips. Clin Chem. 2000 Dec;46(12):1916-22.
pubmed_id:11106323
5:
reference_text:Rosenbaum K, Jahnke K, Curti B, Hagen WR, Schnackerz KD, Vanoni MA: Porcine recombinant dihydropyrimidine dehydrogenase: comparison of the spectroscopic and catalytic properties of the wild-type and C671A mutant enzymes. Biochemistry. 1998 Dec 15;37(50):17598-609.
pubmed_id:9860876
6:
reference_text:Sumi S, Kidouchi K, Kondou M, Hayashi K, Dobashi K, Kouwaki M, Togari H, Wada Y: Possible prediction of adverse reactions to fluorouracil by the measurement of urinary dihydrothymine and thymine. Int J Mol Med. 1998 Oct;2(4):477-82.
pubmed_id:9857238
7:
reference_text:Van Kuilenburg AB, Van Lenthe H, Van Gennip AH: Identification and tissue-specific expression of a NADH-dependent activity of dihydropyrimidine dehydrogenase in man. Anticancer Res. 1996 Jan-Feb;16(1):389-94.
pubmed_id:8615641
8:
reference_text:Kobayashi K, Sumi S, Kidouchi K, Mizuno I, Mohri N, Fukui T, Akamo Y, Takeyama H, Manabe T: [A case of gastric cancer with decreased dihydropyrimidine dehydrogenase activity]. Gan To Kagaku Ryoho. 1998 Jul;25(8):1217-9.
pubmed_id:9679586
9:
reference_text:Sumi S, Imaeda M, Kidouchi K, Ohba S, Hamajima N, Kodama K, Togari H, Wada Y: Population and family studies of dihydropyrimidinuria: prevalence, inheritance mode, and risk of fluorouracil toxicity. Am J Med Genet. 1998 Jul 24;78(4):336-40.
pubmed_id:9714435