Human Metabolome Database: Showing metabocard for Dihydrothymine (HMDB0000079)

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Identification Taxonomy Ontology Physical properties Spectra Biological properties Concentrations Links References enzymes (2) Show 2 proteins XML

enzymes (2) Show 2 proteins

Record Information

Version

4.0

Status

Detected and Quantified

Creation Date

2005-11-16 15:48:42 UTC

Update Date

2020-02-27 20:29:29 UTC

HMDB ID

HMDB0000079

Secondary Accession Numbers

HMDB00079

Metabolite Identification

Common Name

Dihydrothymine

Description

Dihydrothymine 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 to 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 backflow of acidic stomach contents into the esophagus (gastroesophageal reflux) and recurrent episodes of vomiting.

Structure

MOL SDF PDB SMILES InChI

Synonyms

Value	Source
5,6-Dihydro-5-methyluracil	ChEBI
5-Methyl-5,6-dihydrouracil	ChEBI
5,6-Dihydrothymine	HMDB
5-Methyl-hydrouracil	HMDB
5-Methyldihydropyrimidine-2,4(1H,3H)-dione	HMDB
Dihydro-5-methyl-2,4(1H,3H)-pyrimidinedione	HMDB
5-Methyldihydrouracil	HMDB
5,6-Dihydrothymine, (S)-isomer	HMDB

Chemical Formula

C₅H₈N₂O₂

Average Molecular Weight

128.1292

Monoisotopic Molecular Weight

128.05857751

IUPAC Name

5-methyl-1,3-diazinane-2,4-dione

Traditional Name

dihydrothymine

CAS Registry Number

696-04-8

SMILES

CC1CNC(=O)NC1=O

InChI Identifier

InChI=1S/C5H8N2O2/c1-3-2-6-5(9)7-4(3)8/h3H,2H2,1H3,(H2,6,7,8,9)

InChI Key

NBAKTGXDIBVZOO-UHFFFAOYSA-N

Chemical Taxonomy

Description

belongs to the class of organic compounds known as hydropyrimidines. Hydropyrimidines are compounds containing a hydrogenated pyrimidine ring (i.e. containing less than the maximum number of double bonds.).

Kingdom

Organic compounds

Super Class

Organoheterocyclic compounds

Class

Diazines

Sub Class

Pyrimidines and pyrimidine derivatives

Direct Parent

Hydropyrimidines

Alternative Parents

Substituents

5,6-dihydropyrimidine
Hydropyrimidine
Azacycle
Organic 1,3-dipolar compound
Propargyl-type 1,3-dipolar organic compound
Organic nitrogen compound
Organic oxygen compound
Organopnictogen compound
Hydrocarbon derivative
Organooxygen compound
Organonitrogen compound
Aliphatic heteromonocyclic compound

Molecular Framework

Aliphatic heteromonocyclic compounds

External Descriptors

pyrimidone (CHEBI:27468 )
a base derivative (DIHYDRO-THYMINE )
a pyrimidine-related compound (DIHYDRO-THYMINE )

Ontology

Physiological effect

Health effect:

Health condition:

Beta-ureidopropionase deficiency

Disposition

Route of exposure:

Enteral:

Ingestion

Source:

Biological:

Animal

Plant:

Biological location:

Organ and components:

Prostate

Biofluid and excreta:

Subcellular:

Cytoplasm

Process

Naturally occurring process:

Metabolite

Physical Properties

State

Solid

Experimental Properties

Property	Value	Reference
Melting Point	Not Available	Not Available
Boiling Point	Not Available	Not Available
Water Solubility	Not Available	Not Available
LogP	Not Available	Not Available

Predicted Properties

Property	Value	Source
Water Solubility	18.7 g/L	ALOGPS
logP	-0.8	ALOGPS
logP	-0.67	ChemAxon
logS	-0.84	ALOGPS
pKa (Strongest Acidic)	11.7	ChemAxon
pKa (Strongest Basic)	-7.4	ChemAxon
Physiological Charge	0	ChemAxon
Hydrogen Acceptor Count	2	ChemAxon
Hydrogen Donor Count	2	ChemAxon
Polar Surface Area	58.2 Å²	ChemAxon
Rotatable Bond Count	0	ChemAxon
Refractivity	30.32 m³·mol⁻¹	ChemAxon
Polarizability	12.03 Å³	ChemAxon
Number of Rings	1	ChemAxon
Bioavailability	Yes	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	No	ChemAxon
Veber's Rule	No	ChemAxon
MDDR-like Rule	No	ChemAxon

Spectra

Spectrum Type	Description	Splash Key	View
GC-MS	GC-MS Spectrum - GC-MS (1 TMS)	splash10-000i-5900000000-0b84b9786838d29e07ab	Spectrum
GC-MS	GC-MS Spectrum - GC-MS (2 TMS)	splash10-0zmi-8980000000-d75d30c6e5fdb4643aa5	Spectrum
GC-MS	GC-MS Spectrum - GC-MS (Non-derivatized)	splash10-000i-5900000000-0b84b9786838d29e07ab	Spectrum
GC-MS	GC-MS Spectrum - GC-MS (Non-derivatized)	splash10-0zmi-8980000000-d75d30c6e5fdb4643aa5	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	splash10-004i-9300000000-05ab95b9effabc03847d	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)	splash10-004i-8900000000-db662635cbae4d48204b	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)	splash10-0006-9000000000-c3960ffe99d74c617000	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)	splash10-0006-9000000000-9a6c2715f931ff084157	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-004i-0900000000-b0b2721bf2e4a74bbba2	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-0a4l-9100000000-b89dfebf5db699f3651c	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-052f-9000000000-97f152f0bbe6fb600c5c	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-004i-3900000000-98c26fdc1559c4c1afc2	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-0006-9000000000-320f4c88705757a63b75	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-0006-9000000000-76fbb95e0354defdb94e	Spectrum
MS	Mass Spectrum (Electron Ionization)	splash10-004l-9200000000-873ae62dcdf602237ec1	Spectrum
1D NMR	1H NMR Spectrum	Not Available	Spectrum
1D NMR	1H NMR Spectrum	Not Available	Spectrum
1D NMR	13C NMR Spectrum	Not Available	Spectrum
2D NMR	[1H,13C] 2D NMR Spectrum	Not Available	Spectrum

Biological Properties

Cellular Locations

Cytoplasm

Biospecimen Locations

Blood
Cerebrospinal Fluid (CSF)
Feces
Saliva
Urine

Tissue Locations

Prostate

Pathways

Name	SMPDB/Pathwhiz	KEGG
Pyrimidine Metabolism
Beta Ureidopropionase Deficiency		Not Available
UMP Synthase Deficiency (Orotic Aciduria)		Not Available
Dihydropyrimidinase Deficiency		Not Available
MNGIE (Mitochondrial Neurogastrointestinal Encephalopathy)		Not Available

Normal Concentrations

Biospecimen	Status	Value	Age	Sex	Condition	Reference	Details
Blood	Expected but not Quantified		Not Available	Not Available	Normal		details
Cerebrospinal Fluid (CSF)	Detected and Quantified	1.1 +/- 0.3 uM	Adult (>18 years old)	Not Specified	Normal	15385443	details
Feces	Detected but not Quantified		Adult (>18 years old)	Both	Normal	29808030	details
Saliva	Detected but not Quantified		Adult (>18 years old)	Male	Normal	22308371	details
Saliva	Detected but not Quantified		Adult (>18 years old)	Male	Normal	22308371	details
Saliva	Detected but not Quantified		Adult (>18 years old)	Male	Normal	22308371	details
Saliva	Detected but not Quantified		Adult (>18 years old)	Male	Normal	22308371	details
Saliva	Detected but not Quantified		Adult (>18 years old)	Male	Normal	22308371	details
Saliva	Detected but not Quantified		Adult (>18 years old)	Male	Normal	22308371	details
Saliva	Detected but not Quantified		Adult (>18 years old)	Male	Normal	22308371	details
Saliva	Detected but not Quantified		Adult (>18 years old)	Male	Normal	22308371	details
Saliva	Detected but not Quantified		Adult (>18 years old)	Male	Normal	22308371	details
Saliva	Detected but not Quantified		Adult (>18 years old)	Male	Normal	22308371	details
Urine	Detected and Quantified	0.4 umol/mmol creatinine	Adult (>18 years old)	Both	Normal	12798197	details
Urine	Detected and Quantified	5.00 (0.00-10.00) umol/mmol creatinine	Adult (>18 years old)	Both	Normal	16613999	details
Urine	Detected and Quantified	0-3 umol/mmol creatinine	Children (1 - 18 years old)	Both	Normal	BC Children's Hos...	details
Urine	Detected and Quantified	2.4 (1.3-4.4) umol/mmol creatinine	Adult (>18 years old)	Both	Normal	24023812	details
Urine	Detected and Quantified	8.736 +/- 1.827 umol/mmol creatinine	Children (1 - 13 years old)	Not Specified	Normal	Mordechai, Hien, ...	details
Urine	Detected and Quantified	0.40 (0.17-0.64) umol/mmol creatinine	Adult (>18 years old)	Male	Normal	9857238	details
Urine	Detected and Quantified	<0.6 umol/mmol creatinine	Infant (0-1 year old)	Both	Normal	30817767	details
Urine	Detected and Quantified	0.57 (0.21-0.94) umol/mmol creatinine	Adult (>18 years old)	Female	Normal	9857238	details

Abnormal Concentrations

Biospecimen	Status	Value	Age	Sex	Condition	Reference	Details
Cerebrospinal Fluid (CSF)	Detected and Quantified	0.0 - 24.0 uM	Not Specified	Both	Dihydropyrimidinase deficiency	17383919	details
Cerebrospinal Fluid (CSF)	Detected and Quantified	4.0 - 5.2 uM	Adult (>18 years old)	Not Specified	Beta-ureidopropionase deficiency	15385443	details
Urine	Detected and Quantified	11.664 +/- 5.285 umol/mmol creatinine	Children (1 - 13 years old)	Not Specified	Eosinophilic esophagitis	Mordechai, Hien, ...	details

Associated Disorders and Diseases

Disease References

Dihydropyrimidinase deficiency
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:17383919 ]
Beta-ureidopropionase deficiency
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:15385443 ]
Eosinophilic esophagitis
(). Mordechai, Hien, and David S. Wishart. .

Associated OMIM IDs

222748 (Dihydropyrimidinase deficiency)
613161 (Beta-ureidopropionase deficiency)
610247 (Eosinophilic esophagitis)

External Links

DrugBank ID

Not Available

Phenol Explorer Compound ID

Not Available

FoodDB ID

FDB021892

KNApSAcK ID

Not Available

Chemspider ID

84456

KEGG Compound ID

C00906

BioCyc ID

Not Available

BiGG ID

Wikipedia Link

METLIN ID

PubChem Compound

PDB ID

Not Available

ChEBI ID

27468

Food Biomarker Ontology

Not Available

VMH ID

Not Available

References

Synthesis Reference

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.

Material Safety Data Sheet (MSDS)

Download (PDF)

General References

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:9323563 ]
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:11106323 ]
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:12798197 ]
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:9860876 ]
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:9857238 ]
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:8615641 ]
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:9679586 ]
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:9714435 ]
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:19212411 ]

Enzymes

Enzyme Details

1. Dihydropyrimidinase

General function:: Involved in hydrolase activity
Specific function:: Catalyzes the second step of the reductive pyrimidine degradation, the reversible hydrolytic ring opening of dihydropyrimidines. Can catalyze the ring opening of 5,6-dihydrouracil to N-carbamyl-alanine and of 5,6-dihydrothymine to N-carbamyl-amino isobutyrate.
Gene Name:: DPYS
Uniprot ID:: Q14117
Molecular weight:: 56629.36

Reactions

Dihydrothymine + Water → Ureidoisobutyric acid	details

Enzyme Details

2. Dihydropyrimidine dehydrogenase [NADP(+)]

General function:: Involved in electron carrier activity
Specific function:: Involved in pyrimidine base degradation. Catalyzes the reduction of uracil and thymine. Also involved the degradation of the chemotherapeutic drug 5-fluorouracil.
Gene Name:: DPYD
Uniprot ID:: Q12882
Molecular weight:: 111400.32

Reactions

Dihydrothymine + NADP → Thymine + NADPH + Hydrogen Ion	details

Showing metabocard for Dihydrothymine (HMDB0000079)

Structure for HMDB0000079 (Dihydrothymine)

Enzymes

Reactions

Reactions