Target type: biologicalprocess
The chemical reactions and pathways resulting in the formation of a 2'-deoxyribonucleotide, a compound consisting of 2'-deoxyribonucleoside (a base linked to a 2'-deoxyribose sugar) esterified with a phosphate group at either the 3' or 5'-hydroxyl group of the sugar. [GOC:mah]
The 2'-deoxyribonucleotide biosynthetic process is a crucial step in DNA replication and repair. It involves the conversion of ribonucleotides (building blocks of RNA) into deoxyribonucleotides (building blocks of DNA). This process is catalyzed by the enzyme ribonucleotide reductase (RNR).
RNR utilizes a complex mechanism to reduce the 2'-hydroxyl group of ribonucleotides to a hydrogen atom, producing the corresponding deoxyribonucleotide. The enzyme employs a radical mechanism, involving a tyrosyl radical that is generated by a diiron center within the enzyme.
The process can be divided into two main steps:
1. **Reduction of the ribonucleotide:** The ribonucleotide substrate binds to the enzyme, and the tyrosyl radical initiates a chain of electron transfers, ultimately leading to the reduction of the 2'-hydroxyl group. This reduction step requires reducing equivalents, which are provided by a variety of reductants, including NADPH and thioredoxin.
2. **Release of the deoxyribonucleotide:** Once the reduction is complete, the deoxyribonucleotide is released from the enzyme.
The 2'-deoxyribonucleotide biosynthetic process is highly regulated to ensure that DNA replication and repair proceed efficiently and without errors. The activity of RNR is controlled by various factors, including the availability of substrates, the cellular redox state, and the presence of specific regulatory proteins.
Disruptions in this process can lead to a variety of cellular defects, including DNA damage, genomic instability, and cell death. Therefore, the 2'-deoxyribonucleotide biosynthetic pathway is essential for maintaining genomic integrity and normal cellular function.'
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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 |