Target type: biologicalprocess
The chemical reactions and pathways involving thymidine, deoxyribosylthymine thymine 2-deoxyriboside, a deoxynucleoside very widely distributed but occurring almost entirely as phosphoric esters in deoxynucleotides and deoxyribonucleic acid, DNA. [GOC:go_curators]
Thymidine metabolism is a crucial biological process involved in the synthesis and degradation of thymidine, a nucleoside essential for DNA replication and repair. This process is tightly regulated and plays a vital role in cell proliferation, differentiation, and genomic integrity.
**Thymidine Synthesis:**
* De novo synthesis: Thymidine is synthesized from deoxyuridine monophosphate (dUMP) through a two-step enzymatic reaction catalyzed by thymidylate synthase (TS). This enzyme utilizes dihydrofolate reductase (DHFR) to convert dihydrofolate to tetrahydrofolate, a crucial cofactor for TS.
* Salvage pathway: Thymidine can also be obtained through the salvage pathway, where it is recovered from degraded DNA or through dietary sources. This pathway involves the phosphorylation of thymidine to thymidine monophosphate (TMP) by thymidine kinase (TK).
**Thymidine Degradation:**
* Catabolism: Thymidine is degraded by the enzyme thymidine phosphorylase (TP), which cleaves it into thymine and deoxyribose-1-phosphate.
* Thymine metabolism: Thymine is further metabolized to uracil and eventually to β-aminoisobutyrate.
**Regulation of Thymidine Metabolism:**
* Enzyme regulation: The activity of key enzymes involved in thymidine metabolism, such as TS, DHFR, and TK, is tightly regulated by various factors, including substrate availability, cellular growth conditions, and specific inhibitors.
* Feedback regulation: The levels of thymidine and its metabolites can feedback regulate the synthesis and degradation pathways, ensuring appropriate levels of the nucleoside.
**Clinical Significance:**
* Cancer therapy: The key enzymes involved in thymidine metabolism are potential targets for anticancer drugs. Drugs that inhibit TS or DHFR, such as methotrexate and 5-fluorouracil, are widely used in cancer treatment.
* Immune deficiencies: Defects in thymidine metabolism can lead to various immune deficiencies, such as severe combined immunodeficiency (SCID).
* DNA repair: Thymidine metabolism plays a crucial role in DNA repair mechanisms, and dysregulation of this process can contribute to genetic instability and cancer development.
In summary, thymidine metabolism is a complex and essential biological process involving the synthesis, degradation, and regulation of this crucial nucleoside. It plays a critical role in cell proliferation, DNA replication and repair, and has significant implications for human health and disease.'
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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 kinase, cytosolic | A thymidine kinase, cytosolic that is encoded in the genome of human. [PRO:DNx, UniProtKB:P04183] | Homo sapiens (human) |
| Thymidine kinase 2, mitochondrial | A thymidine kinase 2, mitochondrial that is encoded in the genome of human. [PRO:DNx, UniProtKB:O00142] | Homo sapiens (human) |
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| thymidine | pyrimidine 2'-deoxyribonucleoside | Escherichia coli metabolite; human metabolite; metabolite; mouse metabolite | |
| 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 |
| cytarabine | beta-D-arabinoside; monosaccharide derivative; pyrimidine nucleoside | antimetabolite; antineoplastic agent; antiviral agent; immunosuppressive agent | |
| thymidine monophosphate | dTMP : The neutral species of thymidine 5'-monophosphate (2'-deoxythymidine 5'-monophosphate). Thymidine Monophosphate: 5-Thymidylic acid. A thymine nucleotide containing one phosphate group esterified to the deoxyribose moiety. | thymidine 5'-monophosphate | fundamental metabolite |
| deoxyuridine | pyrimidine 2'-deoxyribonucleoside | Escherichia coli metabolite; human metabolite; mouse metabolite; Saccharomyces cerevisiae metabolite | |
| 2'-deoxyadenosine | 2'-deoxyformycin A: RN not in Chemline 9/85; RN and structure given in first source | purine 2'-deoxyribonucleoside; purines 2'-deoxy-D-ribonucleoside | Escherichia coli metabolite; human metabolite; mouse metabolite; Saccharomyces cerevisiae metabolite |
| stavudine | stavudine : A nucleoside analogue obtained by formal dehydration across positions 2 and 3 of thymidine. An inhibitor of HIV-1 reverse transcriptase Stavudine: A dideoxynucleoside analog that inhibits reverse transcriptase and has in vitro activity against HIV. | dihydrofuran; nucleoside analogue; organic molecular entity | antimetabolite; antiviral agent; EC 2.7.7.49 (RNA-directed DNA polymerase) inhibitor |
| vidarabine | adenine arabinoside : A purine nucleoside in which adenine is attached to arabinofuranose via a beta-N(9)-glycosidic bond. | beta-D-arabinoside; purine nucleoside | antineoplastic agent; bacterial metabolite; nucleoside antibiotic |
| zidovudine | zidovudine : A pyrimidine 2',3'-dideoxyribonucleoside compound having a 3'-azido substituent and thymine as the nucleobase. Zidovudine: A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by an azido group. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. The compound is a potent inhibitor of HIV replication, acting as a chain-terminator of viral DNA during reverse transcription. It improves immunologic function, partially reverses the HIV-induced neurological dysfunction, and improves certain other clinical abnormalities associated with AIDS. Its principal toxic effect is dose-dependent suppression of bone marrow, resulting in anemia and leukopenia. | azide; pyrimidine 2',3'-dideoxyribonucleoside | antimetabolite; antiviral drug; HIV-1 reverse transcriptase inhibitor |
| fialuridine | |||
| thymine arabinoside | thymine arabinoside: selectively inhibits replication of herpes simplex virus | N-glycosyl compound | |
| 2',3'-dideoxythymidine | |||
| 2',3'-didehydro-2',3'-dideoxyuridine | |||
| 3'-azido-3'-deoxythymidine 5'phosphate | 3'-azido-3'-deoxythymidine 5'phosphate: inhibits thymidylate kinase | ||
| clevudine | |||
| 6-amino-5-bromouracil | |||
| 5-nitro-2'-deoxyuridine | |||
| 5-propyl-2'-deoxyuridine | 5-propyl-2'-deoxyuridine: RN given refers to parent cpd | ||
| 5'-o-dimethyltritylthymidine | |||
| 1-(2-deoxy-2-fluoroarabinofuranosyl)-5-ethyluracil | 1-(2-deoxy-2-fluoroarabinofuranosyl)-5-ethyluracil: RN given refers to (beta-D)-isomer; structure given in first source | ||
| (north)-methanocarbathymidine | (north)-methanocarbathymidine: also called NMCT 1-[(1S,2S,4S,5R)-4-hydroxy-5-(hydroxymethyl)bicyclo[3.1.0]hexan-2-yl]thymine : A carbobicyclic compound that is bicyclo[3.1.0]hexane which is substituted at the 2-pro-S, 4-pro-S and 5-pro-R positions by thymin-1-yl, hydroxy, and hydroxymethyl groups, respectively. | C-glycosyl pyrimidine; carbobicyclic compound; primary alcohol; pyrimidone; secondary alcohol | |
| brivudine | brivudine: anti-herpes agent | ||
| carbocyclic 5-iodo-2'-deoxyuridine | |||
| 5-phenyl-1,3,4-oxadiazole-2-thiol | 5-phenyl-1,3,4-oxadiazole-2-thiol: structure in first source | ||
| 2',3'-didehydro-3'-deoxy-4'-ethynylthymidine | 2',3'-didehydro-3'-deoxy-4'-ethynylthymidine: a highly active anti-HIV agent; structure in first source | ||
| deoxy-4-thiothymidine | 4-thiothymidine: structure in first source | ||
| sorivudine | organic molecular entity | ||
| 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-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 | ||
| acyclovir | acyclovir : An oxopurine that is guanine substituted by a (2-hydroxyethoxy)methyl substituent at position 9. Used in the treatment of viral infections. Acyclovir: A GUANOSINE analog that acts as an antimetabolite. Viruses are especially susceptible. Used especially against herpes. | 2-aminopurines; oxopurine | antimetabolite; antiviral drug |
| deoxyguanosine | purine 2'-deoxyribonucleoside; purines 2'-deoxy-D-ribonucleoside | Escherichia coli metabolite; human metabolite; mouse metabolite; Saccharomyces cerevisiae metabolite | |
| 9-(4-hydroxybutyl)guanine | |||
| 9-arabinofuranosylguanine | 9-arabinofuranosylguanine: RN given refers to (beta)-isomer 9-beta-D-arabinofuranosylguanine : A purine nucleoside in which guanine is attached to arabinofuranose via a beta-N(9)-glycosidic bond. It inhibits DNA synthesis and causes cell death. | beta-D-arabinoside; purine nucleoside | antineoplastic agent; DNA synthesis inhibitor |
| 5'-o-tritylinosine | 5'-O-tritylinosine: structure in first source |