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pyrimidine nucleobase metabolic process

Definition

Target type: biologicalprocess

The chemical reactions and pathways involving pyrimidine nucleobases, 1,3-diazine, organic nitrogenous bases. [GOC:go_curators]

Pyrimidine nucleobase metabolic process is a fundamental biological process responsible for the synthesis, modification, and degradation of pyrimidine nucleobases, essential building blocks of DNA and RNA. This process involves a series of enzymatic reactions that convert simple precursor molecules into complex pyrimidine nucleobases, such as cytosine, thymine, and uracil. These nucleobases are then incorporated into nucleotides, which in turn form the backbone of DNA and RNA, carrying the genetic code and playing crucial roles in cellular functions like replication, transcription, and translation. The pyrimidine metabolic pathway begins with the synthesis of the precursor molecule, carbamoyl phosphate, from glutamine and bicarbonate. Carbamoyl phosphate then reacts with aspartate to form carbamoyl aspartate, which is subsequently converted into dihydroorotate. Dihydroorotate is then oxidized to orotate, which undergoes a series of reactions to form the pyrimidine nucleotide, uridine monophosphate (UMP). UMP can be further phosphorylated to UDP and UTP, which serve as precursors for the synthesis of other pyrimidine nucleotides, such as cytidine triphosphate (CTP) and thymidine triphosphate (TTP). The degradation of pyrimidine nucleobases occurs primarily in the liver, where they are converted to β-alanine, β-aminoisobutyrate, or uracil. These degradation products are then excreted in urine. Disruptions in pyrimidine metabolism can lead to a variety of genetic diseases, including orotic aciduria, which is characterized by an accumulation of orotic acid in the urine, and pyrimidine nucleoside phosphorylase deficiency, which causes a buildup of pyrimidine nucleosides in the blood and tissues. These disorders can lead to various clinical manifestations, including developmental delays, immune deficiencies, and neurological dysfunction.'
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Proteins (3)

ProteinDefinitionTaxonomy
Thymidine phosphorylaseA thymidine phosphorylase that is encoded in the genome of Escherichia coli K-12. [OMA:P07650, PRO:DNx]Escherichia coli K-12
Ribonucleoside-diphosphate reductase large subunitA ribonucleoside-diphosphate reductase large subunit that is encoded in the genome of human. [PRO:DNx, UniProtKB:P23921]Homo sapiens (human)
Thymidine phosphorylaseA thymidine phosphorylase that is encoded in the genome of human. [PRO:DNx, UniProtKB:P19971]Homo sapiens (human)

Compounds (29)

CompoundDefinitionClassesRoles
hydroxyureaone-carbon compound;
ureas
antimetabolite;
antimitotic;
antineoplastic agent;
DNA synthesis inhibitor;
EC 1.17.4.1 (ribonucleoside-diphosphate reductase) inhibitor;
genotoxin;
immunomodulator;
radical scavenger;
teratogenic agent
thymidinepyrimidine 2'-deoxyribonucleosideEscherichia coli metabolite;
human metabolite;
metabolite;
mouse metabolite
floxuridinefloxuridine : A pyrimidine 2'-deoxyribonucleoside compound having 5-fluorouracil as the nucleobase; used to treat hepatic metastases of gastrointestinal adenocarcinomas and for palliation in malignant neoplasms of the liver and gastrointestinal tract.

Floxuridine: An antineoplastic antimetabolite that is metabolized to fluorouracil when administered by rapid injection; when administered by slow, continuous, intra-arterial infusion, it is converted to floxuridine monophosphate. It has been used to treat hepatic metastases of gastrointestinal adenocarcinomas and for palliation in malignant neoplasms of the liver and gastrointestinal tract.
nucleoside analogue;
organofluorine compound;
pyrimidine 2'-deoxyribonucleoside
antimetabolite;
antineoplastic agent;
antiviral drug;
radiosensitizing agent
idoxuridineorganoiodine compound;
pyrimidine 2'-deoxyribonucleoside
antiviral drug;
DNA synthesis inhibitor
uridine diphosphateUridine Diphosphate: A uracil nucleotide containing a pyrophosphate group esterified to C5 of the sugar moiety.pyrimidine ribonucleoside 5'-diphosphate;
uridine 5'-phosphate
Escherichia coli metabolite;
mouse metabolite
bromodeoxyuridineBromodeoxyuridine: A nucleoside that substitutes for thymidine in DNA and thus acts as an antimetabolite. It causes breaks in chromosomes and has been proposed as an antiviral and antineoplastic agent. It has been given orphan drug status for use in the treatment of primary brain tumors.pyrimidine 2'-deoxyribonucleosideantimetabolite;
antineoplastic agent
cytidine diphosphateCytidine Diphosphate: Cytidine 5'-(trihydrogen diphosphate). A cytosine nucleotide containing two phosphate groups esterified to the sugar moiety. Synonyms: CRPP; cytidine pyrophosphate.cytidine 5'-phosphate;
pyrimidine ribonucleoside 5'-diphosphate
Escherichia coli metabolite;
mouse metabolite
trifluridinetrifluridine : A pyrimidine 2'-deoxyribonucleoside compound having 5-trifluoromethyluracil as the nucleobase. An antiviral drug used mainly in the treatment of primary keratoconjunctivitis and recurrent epithelial keratitis.

Trifluridine: An antiviral derivative of THYMIDINE used mainly in the treatment of primary keratoconjunctivitis and recurrent epithelial keratitis due to HERPES SIMPLEX virus. (From Martindale, The Extra Pharmacopoeia, 30th ed, p557)
nucleoside analogue;
organofluorine compound;
pyrimidine 2'-deoxyribonucleoside
antimetabolite;
antineoplastic agent;
antiviral drug;
EC 2.1.1.45 (thymidylate synthase) inhibitor
deoxyuridinepyrimidine 2'-deoxyribonucleosideEscherichia coli metabolite;
human metabolite;
mouse metabolite;
Saccharomyces cerevisiae metabolite
captoprilcaptopril : A L-proline derivative in which L-proline is substituted on nitrogen with a (2S)-2-methyl-3-sulfanylpropanoyl group. It is used as an anti-hypertensive ACE inhibitor drug.

Captopril: A potent and specific inhibitor of PEPTIDYL-DIPEPTIDASE A. It blocks the conversion of ANGIOTENSIN I to ANGIOTENSIN II, a vasoconstrictor and important regulator of arterial blood pressure. Captopril acts to suppress the RENIN-ANGIOTENSIN SYSTEM and inhibits pressure responses to exogenous angiotensin.
alkanethiol;
L-proline derivative;
N-acylpyrrolidine;
pyrrolidinemonocarboxylic acid
antihypertensive agent;
EC 3.4.15.1 (peptidyl-dipeptidase A) inhibitor
2',3'-dideoxythymidine
6-aminothymine6-aminothymine: inhibits degradation of nucleosides (idoxuridine, thymidine) & pyrimidine bases
5-chloro-2'-deoxyuridine
5-(2-propenyl)-2'-deoxyuridine
edoxudinpyrimidine 2'-deoxyribonucleoside
3-cyano-6-hydroxy-4-methyl-2-pyridone3-cyano-6-hydroxy-4-methyl-2-pyridone: structure in first source
6-amino-5-bromouracil
5-hydroxymethyl-2'-deoxyuridinepyrimidine 2'-deoxyribonucleoside
5-formyl-2'-deoxyuridine5-formyl-2'-deoxyuridine: structure given in first source
2,6-dihydroxy-3-cyanopyridine2,6-dihydroxy-3-cyanopyridine: inhibitor of 5-fluorouracil degradation
5-nitro-2'-deoxyuridine
5-cyano-2'-deoxyuridine5-cyano-2'-deoxyuridine: structure in first source
5-phenyl-1,3,4-oxadiazole-2-thiol5-phenyl-1,3,4-oxadiazole-2-thiol: structure in first source
ma-1tipiracil : A member of the class of pyrimidones that is uracil substituted by chloro and (2-iminopyrrolidin-1-yl)methyl groups at positions 5 and 6 respectively. Used (as the hydrochloride salt) in combination with trifluridine, a nucleoside metabolic inhibitor, for treatment of advanced/relapsed unresectable colorectal cancer.

tipiracil: inhibits thymidine phosphorylase
carboxamidine;
organochlorine compound;
pyrimidone;
pyrrolidines
antineoplastic agent;
EC 2.4.2.4 (thymidine phosphorylase) inhibitor
5-(1-propenyl)-2'-deoxyuridine5-(1-propenyl)-2'-deoxyuridine: has anti-herpes activity; structure in first source
1-aminoadenosine1-aminoadenosine: structure
5-chloro-6-(1-(2-iminopyrrolidinyl) methyl)uracil hydrochloridetipiracil hydrochloride : A hydrochloride obtained by combining tipiracil with one equivalent of hydrochloric acid. Used in combination with trifluridine, a nucleoside metabolic inhibitor, for treatment of advanced/relapsed unresectable colorectal cancer.hydrochloride;
iminium salt
antineoplastic agent;
EC 2.4.2.4 (thymidine phosphorylase) inhibitor
sesone7-deazaxanthine: structure in first source
5'-o-tritylinosine5'-O-tritylinosine: structure in first source