Target type: biologicalprocess
The chemical reactions and pathways involving any pyrimidine nucleoside, one of a family of organic molecules consisting of a pyrimidine base covalently bonded to ribose (a ribonucleoside) or deoxyribose (a deoxyribonucleoside). [GOC:jl, ISBN:0140512713]
Pyrimidine nucleoside metabolic process is a fundamental biological pathway responsible for the synthesis, utilization, and degradation of pyrimidine nucleosides. These molecules, composed of a pyrimidine base (cytosine, uracil, or thymine) linked to a ribose or deoxyribose sugar, are essential building blocks for DNA and RNA, the genetic material of all living organisms.
**1. De Novo Synthesis:** The de novo pathway is the primary route for synthesizing pyrimidine nucleotides. It begins with the condensation of aspartate and carbamoyl phosphate to form carbamoylaspartate, followed by a series of enzymatic steps involving dihydroorotate dehydrogenase, orotate phosphoribosyltransferase, and orotidine 5'-phosphate decarboxylase. These reactions ultimately lead to the formation of UMP (uridine monophosphate), the precursor of other pyrimidine nucleotides.
**2. Salvage Pathway:** The salvage pathway provides an alternative route for generating pyrimidine nucleotides by recycling pre-existing bases or nucleosides. This pathway relies on enzymes like uridine phosphorylase and thymidine kinase, which convert uracil and thymine into their respective monophosphates.
**3. Nucleotide Interconversion:** Pyrimidine nucleotides can be interconverted through a series of enzymatic reactions. For instance, UMP can be converted to CMP (cytidine monophosphate) by CTP synthetase.
**4. Degradation:** The breakdown of pyrimidine nucleotides occurs primarily in the liver. Enzymes like uracil-DNA glycosylase and thymine-DNA glycosylase remove damaged or modified pyrimidine bases from DNA. Further degradation leads to the formation of β-alanine, β-aminoisobutyrate, and ammonia.
**5. Regulation:** The synthesis and degradation of pyrimidine nucleotides are tightly regulated to maintain cellular homeostasis. Feedback mechanisms and allosteric regulation ensure that nucleotide levels are adequate for DNA replication and RNA transcription, but not excessive, preventing potential cytotoxic effects.
**6. Clinical Significance:** Dysregulation of pyrimidine nucleoside metabolism can lead to a range of human diseases. Deficiencies in enzymes involved in the pathway can cause genetic disorders like orotic aciduria and Lesch-Nyhan syndrome. Conversely, aberrant nucleotide metabolism can contribute to the development of cancers, autoimmune diseases, and other conditions.
Overall, the pyrimidine nucleoside metabolic process is a complex and tightly regulated pathway essential for maintaining cellular function and survival. Its intricate mechanisms and diverse roles highlight its importance in various biological processes and its relevance to human health.'
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Protein | Definition | Taxonomy |
---|---|---|
Thymidine phosphorylase | A thymidine phosphorylase that is encoded in the genome of Escherichia coli K-12. [OMA:P07650, PRO:DNx] | Escherichia coli K-12 |
Thymidine phosphorylase | A thymidine phosphorylase that is encoded in the genome of human. [PRO:DNx, UniProtKB:P19971] | Homo sapiens (human) |
Compound | Definition | Classes | Roles |
---|---|---|---|
thymidine | pyrimidine 2'-deoxyribonucleoside | Escherichia coli metabolite; human metabolite; metabolite; mouse metabolite | |
floxuridine | floxuridine : 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 |
idoxuridine | organoiodine compound; pyrimidine 2'-deoxyribonucleoside | antiviral drug; DNA synthesis inhibitor | |
bromodeoxyuridine | Bromodeoxyuridine: 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'-deoxyribonucleoside | antimetabolite; antineoplastic agent |
trifluridine | trifluridine : 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 |
deoxyuridine | pyrimidine 2'-deoxyribonucleoside | Escherichia coli metabolite; human metabolite; mouse metabolite; Saccharomyces cerevisiae metabolite | |
captopril | captopril : 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-aminothymine | 6-aminothymine: inhibits degradation of nucleosides (idoxuridine, thymidine) & pyrimidine bases | ||
5-chloro-2'-deoxyuridine | |||
5-(2-propenyl)-2'-deoxyuridine | |||
edoxudin | pyrimidine 2'-deoxyribonucleoside | ||
3-cyano-6-hydroxy-4-methyl-2-pyridone | 3-cyano-6-hydroxy-4-methyl-2-pyridone: structure in first source | ||
6-amino-5-bromouracil | |||
5-hydroxymethyl-2'-deoxyuridine | pyrimidine 2'-deoxyribonucleoside | ||
5-formyl-2'-deoxyuridine | 5-formyl-2'-deoxyuridine: structure given in first source | ||
2,6-dihydroxy-3-cyanopyridine | 2,6-dihydroxy-3-cyanopyridine: inhibitor of 5-fluorouracil degradation | ||
5-nitro-2'-deoxyuridine | |||
5-cyano-2'-deoxyuridine | 5-cyano-2'-deoxyuridine: structure in first source | ||
5-phenyl-1,3,4-oxadiazole-2-thiol | 5-phenyl-1,3,4-oxadiazole-2-thiol: structure in first source | ||
ma-1 | tipiracil : 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'-deoxyuridine | 5-(1-propenyl)-2'-deoxyuridine: has anti-herpes activity; structure in first source | ||
5-chloro-6-(1-(2-iminopyrrolidinyl) methyl)uracil hydrochloride | tipiracil 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 |
sesone | 7-deazaxanthine: structure in first source | ||
5'-o-tritylinosine | 5'-O-tritylinosine: structure in first source |