Target type: biologicalprocess
The directed movement of pyrimidine nucleobases, one of the two classes of nitrogen-containing ring compounds found in DNA and RNA, into, out of or within a cell, or between cells, by means of some agent such as a transporter or pore. [GOC:ai]
Pyrimidine nucleobase transport is a crucial process in cellular metabolism, ensuring the availability of essential building blocks for nucleic acid synthesis, nucleotide biosynthesis, and various metabolic pathways. The primary pyrimidine nucleobases are cytosine (C), thymine (T), and uracil (U). Their transport across cell membranes is facilitated by a specialized family of membrane transporters, primarily belonging to the solute carrier (SLC) family.
The transport process involves a complex interplay of factors, including membrane potential, concentration gradients, and specific transporter proteins. Here's a detailed breakdown:
1. **Transport Systems:** The key players in pyrimidine nucleobase transport are SLC transporters, specifically SLC23 and SLC29 families. SLC23 members, such as hENT1 and hENT2 (human equilibrative nucleoside transporter 1 and 2), mediate facilitated diffusion of pyrimidine nucleobases across the cell membrane. This process is driven by the concentration gradient, allowing nucleobases to move from areas of high concentration to low concentration. In contrast, SLC29 members, including hCNT1 and hCNT2 (human concentrative nucleoside transporter 1 and 2), utilize active transport mechanisms. They couple the transport of pyrimidine nucleobases with the inward movement of sodium ions, enabling the accumulation of nucleobases against their concentration gradients.
2. **Regulation:** The activity of pyrimidine nucleobase transporters is finely regulated by various mechanisms, including:
* **Substrate Specificity:** Different transporters exhibit varying affinities for specific pyrimidine nucleobases. For instance, hENT1 has a higher affinity for uracil and thymine compared to cytosine.
* **Cellular Signaling:** Cellular signals, such as growth factors and hormones, can modulate transporter expression and activity, fine-tuning pyrimidine nucleobase uptake based on cellular needs.
* **Feedback Mechanisms:** The intracellular concentration of pyrimidine nucleobases can feedback regulate transporter activity, preventing excessive accumulation.
3. **Physiological Significance:** Pyrimidine nucleobase transport is critical for:
* **DNA and RNA Synthesis:** Pyrimidine nucleobases are essential building blocks for DNA and RNA, ensuring the proper functioning of genetic material.
* **Nucleotide Metabolism:** Pyrimidine nucleobases are utilized in various metabolic pathways, including nucleotide synthesis, where they are incorporated into nucleotides, the building blocks of nucleic acids.
* **Cellular Growth and Differentiation:** Adequate pyrimidine nucleobase availability is essential for cellular proliferation and development.
4. **Clinical Relevance:** Dysregulation of pyrimidine nucleobase transport can lead to various pathological conditions:
* **Cancer:** Altered transporter expression and activity have been implicated in cancer development and progression.
* **Neurological Disorders:** Impairments in pyrimidine nucleobase transport can contribute to neurological dysfunction and neurodegenerative diseases.
* **Metabolic Disorders:** Dysregulation of pyrimidine nucleobase metabolism can lead to various metabolic disorders, including genetic defects in nucleotide biosynthesis.
In summary, pyrimidine nucleobase transport is a highly regulated and essential process that ensures the availability of these vital molecules for various cellular functions. Understanding the intricacies of pyrimidine nucleobase transport mechanisms and their regulation is crucial for advancing our knowledge of cellular metabolism, disease pathogenesis, and potential therapeutic interventions.'
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Protein | Definition | Taxonomy |
---|---|---|
Sodium/nucleoside cotransporter 1 | A sodium/nucleoside cotransporter 1 that is encoded in the genome of human. [PRO:DNx, UniProtKB:O00337] | Homo sapiens (human) |
Solute carrier family 28 member 3 | A solute carrier family 28 member 3 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q9HAS3] | Homo sapiens (human) |
Sodium/nucleoside cotransporter 2 | A sodium/nucleoside cotransporter 2 that is encoded in the genome of human. [PRO:DNx, UniProtKB:O43868] | Homo sapiens (human) |
Compound | Definition | Classes | Roles |
---|---|---|---|
phloretin | dihydrochalcones | antineoplastic agent; plant metabolite | |
floxuridine | floxuridine : A pyrimidine 2'-deoxyribonucleoside compound having 5-fluorouracil as the nucleobase; used to treat hepatic metastases of gastrointestinal adenocarcinomas and for palliation in malignant neoplasms of the liver and gastrointestinal tract. Floxuridine: An antineoplastic antimetabolite that is metabolized to fluorouracil when administered by rapid injection; when administered by slow, continuous, intra-arterial infusion, it is converted to floxuridine monophosphate. It has been used to treat hepatic metastases of gastrointestinal adenocarcinomas and for palliation in malignant neoplasms of the liver and gastrointestinal tract. | nucleoside analogue; organofluorine compound; pyrimidine 2'-deoxyribonucleoside | antimetabolite; antineoplastic agent; antiviral drug; radiosensitizing agent |
uridine | uridines | drug metabolite; fundamental metabolite; human metabolite | |
phlorhizin | aryl beta-D-glucoside; dihydrochalcones; monosaccharide derivative | antioxidant; plant metabolite | |
resacetophenone | 2',4'-dihydroxyacetophenone : A dihydroxyacetophenone that is acetophenone carrying hydroxy substituents at positions 2' and 4'. resacetophenone: structure in first source | dihydroxyacetophenone; resorcinols | plant metabolite |
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 | |
2,4,6-trihydroxyacetophenone | 2',4',6'-trihydroxyacetophenone : A benzenetriol that is acetophenone in which the hydrogens at positions 2, 4, and 6 on the phenyl group are replaced by hydroxy groups. It is used as a matrix in matrix-assisted laser desorption/ionization (MALDI) mass spectrometry for the analysis of acidic glycans and glycopeptides. monoacetylphloroglucinol: structure in first source | aromatic ketone; benzenetriol; methyl ketone | MALDI matrix material; plant metabolite |
2,6-dihydroxyacetophenone | 2,6-dihydroxyacetophenone: inhibits aminopyrine-N-demethylase in rat liver microsomal preparations | aromatic ketone | |
tecadenoson | tecadenoson: an A1 adenosine receptor agonist | ||
7,8,3'-trihydroxyflavone | 7,8,3'-trihydroxyflavone: a potent small molecule TrkB receptor agonist that protects spiral ganglion neurons from degeneration both in vitro and in vivo | ||
trilobatin | trilobatin : An aryl beta-D-glucoside that is phloretin attached to a beta-D-glucopyranosyl residue at position 4' via a glycosidic linkage. It is isolated from the leaves of the Chinese sweet tea Lithocarpus polystachyus and exhibits significant anti-hyperglycemic, anti-oxidative and anti-inflammatory properties. trilobatin: anti-inflammatory from Lithocarpus polystachyus leaves; structure in first source | aryl beta-D-glucoside; dihydrochalcones; monosaccharide derivative | anti-inflammatory agent; antioxidant; plant metabolite; sweetening agent |