Target type: biologicalprocess
The process in which pyrimidine is transported across a membrane. [GO_REF:0000069, GOC:TermGenie]
Pyrimidine nucleobase transmembrane transport is a critical process in cellular metabolism, ensuring the uptake and export of essential pyrimidine bases like cytosine, thymine, and uracil. These bases are building blocks for DNA and RNA, and their transport across cell membranes is tightly regulated to maintain cellular homeostasis.
The process involves specialized membrane transport proteins known as pyrimidine nucleoside transporters (PNTs). These proteins are embedded within the cell membrane and possess specific binding sites for pyrimidine nucleobases.
**Mechanism:**
The transport of pyrimidine nucleobases typically follows a passive diffusion mechanism, driven by the concentration gradient across the membrane. In other words, bases move from areas of high concentration to areas of low concentration.
* **Uptake:** Cells require pyrimidine bases for nucleotide synthesis and DNA/RNA replication. Therefore, PNTs facilitate the import of these bases from the extracellular environment.
* **Export:** Cells may need to remove excess pyrimidine bases or eliminate damaged or modified bases. PNTs also participate in the export of these bases, maintaining appropriate intracellular concentrations.
**Regulation:**
Pyrimidine nucleobase transport is tightly regulated by several factors:
* **Cellular demand:** The activity of PNTs is often influenced by the cellular requirement for pyrimidine bases. For instance, during rapid cell growth or DNA replication, the transport of these bases is enhanced.
* **Nutritional status:** Dietary intake of pyrimidine bases can affect the expression and activity of PNTs.
* **Hormonal control:** Certain hormones can modulate the expression of PNTs, fine-tuning the transport of pyrimidine bases.
**Clinical relevance:**
Dysregulation of pyrimidine nucleobase transport can lead to various pathological conditions:
* **Cancer:** Abnormal pyrimidine transport can contribute to tumor cell growth and proliferation.
* **Neurological disorders:** Altered pyrimidine transport has been implicated in certain neurological disorders.
* **Genetic diseases:** Defects in specific PNT genes can result in inherited metabolic disorders.
Understanding the intricacies of pyrimidine nucleobase transmembrane transport is crucial for developing new therapies targeting various diseases and understanding cellular metabolism at a fundamental level.'
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| Protein | Definition | Taxonomy |
|---|---|---|
| Equilibrative nucleoside transporter 1 | An equilibrative nucleoside transporter 1 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q99808] | Homo sapiens (human) |
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| dilazep | dilazep : A member of the class of diazepanes that is 1,4-diazepane substituted by 3-[(3,4,5-trimethoxybenzoyl)oxy]propyl groups at positions 1 and 4. It is a potent adenosine uptake inhibitor that exhibits antiplatelet, antianginal and vasodilator properties. Dilazep: Coronary vasodilator with some antiarrhythmic activity. | benzoate ester; diazepane; diester; methoxybenzenes | cardioprotective agent; platelet aggregation inhibitor; vasodilator agent |
| dipyridamole | dipyridamole : A pyrimidopyrimidine that is 2,2',2'',2'''-(pyrimido[5,4-d]pyrimidine-2,6-diyldinitrilo)tetraethanol substituted by piperidin-1-yl groups at positions 4 and 8 respectively. A vasodilator agent, it inhibits the formation of blood clots. Dipyridamole: A phosphodiesterase inhibitor that blocks uptake and metabolism of adenosine by erythrocytes and vascular endothelial cells. Dipyridamole also potentiates the antiaggregating action of prostacyclin. (From AMA Drug Evaluations Annual, 1994, p752) | piperidines; pyrimidopyrimidine; tertiary amino compound; tetrol | adenosine phosphodiesterase inhibitor; EC 3.5.4.4 (adenosine deaminase) inhibitor; platelet aggregation inhibitor; vasodilator agent |
| lidoflazine | Lidoflazine: Coronary vasodilator with some antiarrhythmic action. | diarylmethane | |
| uridine | uridines | drug metabolite; fundamental metabolite; human metabolite | |
| phlorhizin | aryl beta-D-glucoside; dihydrochalcones; monosaccharide derivative | antioxidant; plant metabolite | |
| methylthioinosine | Methylthioinosine: 6-(Methylthio)-9-beta-D-ribofuranosylpurine. An analog of inosine with a methylthio group replacing the hydroxyl group in the 6-position. | purine ribonucleoside; thiopurine | |
| hyaluronoglucosaminidase | kinetin riboside: preferentially induces apoptosis by modulating Bcl-2 family proteins and caspase-3 in cancer cells; structure in first source | purine nucleoside | |
| gemcitabine | gemcitabine : 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 |
| draflazine | draflazine: a nucleoside transport inhibitor; has cardioprotective effect; draflazine is the (-)-enantiomer; R 88016 is the (+)-enantiomer | ||
| adenosine | quinquefolan B: isolated from roots of Panax quinquefolium L.; RN not in Chemline 10/87; RN from Toxlit | adenosines; purines D-ribonucleoside | analgesic; anti-arrhythmia drug; fundamental metabolite; human metabolite; vasodilator agent |
| 4-nitrobenzylthioinosine | 4-nitrobenzylthioinosine: inhibitor of nucleoside transport; acts on ENT1 | purine nucleoside | |
| n(6)-benzyladenosine | N(6)-benzyladenosine: RN given refers to parent cpd | ||
| 6-(4-nitrobenzylthio)guanosine | 6-(4-nitrobenzylthio)guanosine: inhibitor of nucleoside transport | ||
| 5-iodotubercidin | 7-iodotubercidin: inhibits Toxoplasma gondii adenosine kinase | organoiodine compound | |
| n(6)-phenyladenosine | purine nucleoside | ||
| tecadenoson | tecadenoson: an A1 adenosine receptor agonist | ||
| 2-hydroxy-5-nitrobenzylthioguanosine | |||
| n(6)-cyclopentyladenosine | |||
| 6-benzylthioinosine | 6-benzylthioinosine: a subversive substrate of T gondii adenosine kinase; structure in first source |