Target type: biologicalprocess
The chemical reactions and pathways resulting in the formation of a deoxyribonucleoside monophosphate, a compound consisting of a nucleobase linked to a deoxyribose sugar esterified with phosphate on the sugar. [GOC:go_curators, ISBN:0198506732]
Deoxyribonucleoside monophosphate (dNMP) biosynthesis is a fundamental process in all living organisms, responsible for the synthesis of the building blocks of DNA. These building blocks are deoxyadenosine monophosphate (dAMP), deoxycytidine monophosphate (dCMP), deoxyguanosine monophosphate (dGMP), and deoxythymidine monophosphate (dTMP). The process occurs in several steps, and the specific enzymes involved and pathways can differ slightly between organisms.
**1. Reduction of Ribonucleotides to Deoxyribonucleotides:**
The first step is the reduction of ribonucleotides (AMP, CMP, GMP, and UMP) to deoxyribonucleotides (dAMP, dCMP, dGMP, and dUMP) by the enzyme **ribonucleotide reductase**. This enzyme utilizes a complex mechanism involving a free radical intermediate and the cofactor thioredoxin, which is reduced by NADPH.
**2. Deoxythymidine Monophosphate (dTMP) Synthesis:**
dTMP, which is unique to DNA, is synthesized from dUMP through a two-step process:
* **Thymidylate synthase** catalyzes the transfer of a methyl group from tetrahydrofolate (THF) to dUMP, generating dTMP and dihydrofolate (DHF).
* **Dihydrofolate reductase** then reduces DHF back to THF, completing the cycle.
**3. dAMP, dCMP, and dGMP Synthesis:**
dAMP, dCMP, and dGMP are synthesized from their corresponding deoxynucleoside diphosphates (dADP, dCDP, and dGDP), respectively, by **deoxyribonucleoside kinases**.
**4. Interconversion of Deoxyribonucleoside Triphosphates (dNTPs):**
The dNMPs are further phosphorylated to dNTPs (dATP, dCTP, dGTP, and dTTP) by **deoxyribonucleoside diphosphate kinases** and **deoxyribonucleoside triphosphate kinases**. These dNTPs serve as substrates for DNA synthesis by DNA polymerases.
**Overall, deoxyribonucleoside monophosphate biosynthesis is a tightly regulated process, essential for maintaining the integrity and function of DNA. It involves the concerted action of various enzymes, cofactors, and metabolic pathways, ensuring the continuous supply of building blocks for DNA replication and repair.**'
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| Protein | Definition | Taxonomy |
|---|---|---|
| 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'-didehydro-2',3'-dideoxyuridine | |||
| 3'-azido-3'-deoxythymidine 5'phosphate | 3'-azido-3'-deoxythymidine 5'phosphate: inhibits thymidylate kinase | ||
| clevudine | |||
| 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 | |||
| 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 | ||
| 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 |