Page last updated: 2024-10-24

pyrimidine-containing compound salvage

Definition

Target type: biologicalprocess

Any process that generates a pyrimidine-containing compound, a nucleobase, nucleoside, nucleotide or nucleic acid that contains a pyrimidine base, from derivatives of them without de novo synthesis. [GOC:jl]

Pyrimidine-containing compound salvage is a critical biological process that recovers and reuses pre-existing pyrimidine bases, such as uracil, cytosine, and thymine, to synthesize new nucleotides. This pathway is essential for maintaining cellular nucleotide pools and ensuring efficient DNA replication and repair.

The salvage pathway involves a series of enzymatic reactions that convert pre-existing pyrimidine bases into their respective nucleoside monophosphates (NMPs), which are then further phosphorylated to nucleoside diphosphates (NDPs) and triphosphates (NTPs). These NTPs serve as building blocks for DNA and RNA synthesis.

**Key Enzymes and Steps:**

1. **Uracil Phosphoribosyltransferase (UPRT):** This enzyme catalyzes the conversion of uracil to uridine monophosphate (UMP) using phosphoribosyl pyrophosphate (PRPP) as a substrate.
2. **Cytidine Deaminase:** This enzyme removes the amino group from cytosine to form uracil, which can then be salvaged by UPRT.
3. **Thymine Phosphorylase:** This enzyme converts thymine to thymidine, which is then phosphorylated to thymidine monophosphate (TMP) by thymidine kinase.

**Regulation of the Salvage Pathway:**

The salvage pathway is tightly regulated to ensure the proper balance between de novo synthesis and salvage pathways. This regulation is achieved through the following mechanisms:

* **Substrate availability:** The availability of pyrimidine bases from the breakdown of nucleic acids or from the diet influences the activity of salvage enzymes.
* **Feedback inhibition:** The accumulation of nucleotide products can inhibit the activity of salvage enzymes, preventing excessive nucleotide synthesis.
* **Allosteric regulation:** Some salvage enzymes are regulated by allosteric modulators, which can alter their activity and substrate affinity.

**Clinical Significance:**

Defects in the salvage pathway can lead to a variety of genetic disorders, such as orotic aciduria and hereditary orotic aciduria. These disorders are characterized by the accumulation of orotic acid in the urine and can cause severe developmental delays and neurological problems.

**Conclusion:**

Pyrimidine-containing compound salvage is an essential metabolic pathway that ensures the efficient utilization of pre-existing pyrimidine bases. This pathway is tightly regulated to maintain nucleotide homeostasis and support cellular processes that rely on pyrimidine nucleotides, such as DNA replication and repair.'
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Proteins (1)

ProteinDefinitionTaxonomy
Cytidine deaminaseA cytidine deaminase that is encoded in the genome of human. [PRO:DNx, UniProtKB:P32320]Homo sapiens (human)

Compounds (10)

CompoundDefinitionClassesRoles
uridineuridinesdrug metabolite;
fundamental metabolite;
human metabolite
cytidinecytidinesEscherichia coli metabolite;
human metabolite;
mouse metabolite;
Saccharomyces cerevisiae metabolite
cytarabinebeta-D-arabinoside;
monosaccharide derivative;
pyrimidine nucleoside
antimetabolite;
antineoplastic agent;
antiviral agent;
immunosuppressive agent
deoxycytidinepyrimidine 2'-deoxyribonucleosideEscherichia coli metabolite;
human metabolite;
mouse metabolite;
Saccharomyces cerevisiae metabolite
gemcitabinegemcitabine : A 2'-deoxycytidine having geminal fluoro substituents in the 2'-position. An inhibitor of ribonucleotide reductase, gemcitabine is used in the treatment of various carcinomas, particularly non-small cell lung cancer, pancreatic cancer, bladder cancer and breast cancer.organofluorine compound;
pyrimidine 2'-deoxyribonucleoside
antimetabolite;
antineoplastic agent;
antiviral drug;
DNA synthesis inhibitor;
EC 1.17.4.1 (ribonucleoside-diphosphate reductase) inhibitor;
environmental contaminant;
immunosuppressive agent;
photosensitizing agent;
prodrug;
radiosensitizing agent;
xenobiotic
5,6-dihydrouridinedihydrouridine : The uridine derivative obtained by formal hydrogenation of the endocyclic double bond in the uracil ring.uridinesbiomarker
pyrimidin-2-one beta-ribofuranosidepyrimidin-2-one beta-ribofuranoside: RN given refers to (D)-isomer; structurepyrimidine ribonucleosides
2'-fluoro-2'-deoxycytidine
2'-c-methylcytidine2'-C-methylcytidine: structure in first source
psi 61302'-deoxy-2'-fluoro-2'-C-methylcytidine: PSI-6130 is the (beta-D)-isomer; has antiviral activity against hepatitis C virus; structure in first source