Target type: biologicalprocess
The chemical reactions and pathways resulting in the formation of a deoxyribonucleotide, a compound consisting of deoxyribonucleoside (a base linked to a deoxyribose sugar) esterified with a phosphate group at either the 3' or 5'-hydroxyl group of the sugar. [GOC:go_curators, ISBN:0198506732]
Deoxyribonucleotide biosynthesis is a fundamental cellular process that generates the building blocks for DNA replication and repair. This complex pathway involves a series of enzymatic reactions, ultimately producing the four deoxyribonucleotides: deoxyadenosine triphosphate (dATP), deoxyguanosine triphosphate (dGTP), deoxycytidine triphosphate (dCTP), and thymidine triphosphate (dTTP).
The process begins with the reduction of the diphosphate form of the corresponding ribonucleotides (ADP, GDP, CDP, and UDP) to their deoxyribonucleotide counterparts (dADP, dGDP, dCDP, and dUDP). This crucial step is catalyzed by the enzyme **ribonucleotide reductase (RNR)**, which utilizes a complex mechanism involving a tyrosyl radical and a diiron center.
Following reduction, the deoxyribonucleotide diphosphates (dNDPs) are further phosphorylated to their triphosphate forms (dNTPs) by dedicated kinases. These kinases include **deoxyguanosine kinase (dGK)** for dGTP, **deoxycytidine kinase (dCK)** for dCTP, and **thymidine kinase (TK)** for dTTP. dATP is generated by the action of **nucleoside diphosphate kinase (NDPK)**, which can phosphorylate various nucleoside diphosphates, including dADP.
Several regulatory mechanisms ensure the precise control of deoxyribonucleotide biosynthesis. These mechanisms include:
* **Feedback inhibition:** dNTPs can inhibit RNR activity, preventing overproduction of deoxyribonucleotides.
* **Allosteric regulation:** Specific proteins, such as **p53**, can bind to RNR and modulate its activity.
* **Redox regulation:** The activity of RNR is sensitive to cellular redox state, providing a link between metabolic and DNA synthesis processes.
Deoxyribonucleotide biosynthesis is essential for DNA replication and repair, and its dysregulation is implicated in various diseases, including cancer and genetic disorders. Understanding this complex process is crucial for developing therapeutic strategies targeting DNA synthesis pathways.'
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| Protein | Definition | Taxonomy |
|---|---|---|
| Ribonucleoside-diphosphate reductase subunit M2 B | A ribonucleoside-diphosphate reductase subunit M2 B that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q7LG56] | Homo sapiens (human) |
| Ribonucleoside-diphosphate reductase subunit M2 | A ribonucleoside-diphosphate reductase subunit M2 that is encoded in the genome of human. [PRO:DNx, UniProtKB:P31350] | Homo sapiens (human) |
| Ribonucleoside-diphosphate reductase large subunit | A ribonucleoside-diphosphate reductase large subunit that is encoded in the genome of human. [PRO:DNx, UniProtKB:P23921] | Homo sapiens (human) |
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| hydroxyurea | one-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 | |
| uridine diphosphate | Uridine 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 |
| cytidine diphosphate | Cytidine 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 |
| 1-aminoadenosine | 1-aminoadenosine: structure | ||
| 3-aminopyridine-2-carboxaldehyde thiosemicarbazone | 3-aminopyridine-2-carboxaldehyde thiosemicarbazone: a neuroprotective agent; structure given in first source |