Target type: biologicalprocess
The directed movement of the purine ribonucleoside inosine, also known as hypoxanthine riboside, into, out of or within a cell, or between cells, by means of some agent such as a transporter or pore. [PMID:19135251]
Inosine transport is a crucial process that facilitates the movement of inosine, a purine nucleoside, across cell membranes. This process is essential for maintaining cellular homeostasis, particularly in the context of purine metabolism. Inosine, a precursor to guanine and adenine, plays a vital role in DNA and RNA synthesis, as well as in energy production through the adenosine triphosphate (ATP) cycle.
Inosine transport occurs through a complex interplay of membrane transporters. The specific mechanisms vary depending on the cell type and the physiological conditions. Generally, there are two main types of inosine transporters:
1. **Facilitative transporters:** These transporters mediate passive transport of inosine down its concentration gradient, without requiring energy input. They are responsible for the uptake of inosine from the extracellular space into the cell.
2. **Active transporters:** These transporters actively move inosine against its concentration gradient, requiring energy derived from ATP hydrolysis. They play a role in the efflux of inosine from the cell, as well as in its uptake from specific sources.
**Mechanism of Inosine Transport:**
The detailed mechanism of inosine transport remains an active area of research. However, several key factors contribute to its regulation:
* **Concentration gradients:** The concentration difference between the intracellular and extracellular compartments drives the movement of inosine through facilitative transporters.
* **Membrane potential:** The electrical potential across the cell membrane can influence the transport of charged molecules like inosine.
* **Specific transporter proteins:** The expression and activity of specific inosine transporters are regulated by a variety of factors, including hormones, growth factors, and cellular stress.
* **Substrate specificity:** Different transporters exhibit varying degrees of specificity for inosine and other purine nucleosides.
* **Metabolic regulation:** The intracellular levels of purine nucleotides and other metabolites can affect the activity of inosine transporters.
**Physiological Significance:**
Inosine transport is essential for various physiological functions:
* **Purine metabolism:** Inosine transport provides cells with a source of inosine, which is crucial for the synthesis of guanine and adenine, essential components of DNA and RNA.
* **Energy production:** Inosine is a precursor to adenosine, which is a key molecule in energy production through ATP synthesis.
* **Signal transduction:** Inosine can act as a signaling molecule, regulating cell growth and differentiation.
* **Neurotransmission:** Inosine is involved in neurotransmission, particularly in the brain, where it acts as a neuromodulator.
* **Tissue repair:** Inosine has been shown to promote tissue repair in various organs, including the heart, liver, and kidneys.
**Clinical Implications:**
Disruptions in inosine transport can lead to various clinical conditions, including:
* **Purine metabolism disorders:** Deficiencies in inosine transport can result in impaired purine metabolism, leading to neurological and developmental problems.
* **Cancer:** Altered inosine transport has been implicated in cancer development and progression.
* **Neurodegenerative diseases:** Inosine transport dysfunction has been linked to neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease.
**Conclusion:**
Inosine transport is a vital cellular process that plays a crucial role in purine metabolism, energy production, signal transduction, and other physiological functions. Understanding the molecular mechanisms underlying inosine transport is essential for developing new therapeutic strategies for a wide range of diseases.'
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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) |
Equilibrative nucleoside transporter 2 | An equilibrative nucleoside transporter 2 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q14542] | 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 |
---|---|---|---|
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 | |
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 | |
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 | |||
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 | ||
6-benzylthioinosine | 6-benzylthioinosine: a subversive substrate of T gondii adenosine kinase; structure in first source |