folate transmembrane transport
Definition
Target type: biologicalprocess
The process in which a folic acid, or one of its derivatives (dihydrofolate, tetrahydrofolate, methylene-tetrahydrofolate or methyl-tetrahydrofolate) is transported across a membrane. [PMID:24745983]
Folate transmembrane transport is a crucial process for maintaining cellular folate levels, essential for various metabolic reactions, including DNA synthesis, repair, and methylation. Folate, a B vitamin, cannot passively diffuse across cell membranes due to its hydrophilic nature. Therefore, specific membrane-bound transport proteins facilitate its uptake. These proteins belong to the Reduced Folate Carrier (RFC) family, characterized by their ability to transport reduced folates like tetrahydrofolate (THF).
The mechanism of folate transport involves a series of steps:
1. **Binding:** Folate binds to the extracellular domain of the RFC protein.
2. **Conformational Change:** Binding of folate triggers a conformational change in the RFC protein, opening an intracellular channel.
3. **Translocation:** Folate translocates through the channel from the extracellular to the intracellular side of the membrane.
4. **Release:** Folate is released into the cytoplasm, and the RFC protein returns to its original conformation, ready for another cycle.
Folate transport is highly regulated, influenced by factors like:
* **Cellular folate levels:** When cellular folate levels are low, RFC activity increases to facilitate uptake.
* **Dietary folate intake:** Increased dietary folate intake leads to upregulation of RFC expression.
* **Hormones:** Certain hormones, like estrogen and progesterone, can modulate RFC activity.
Mutations in RFC genes can lead to impaired folate transport, resulting in folate deficiency and related health problems.
This process is essential for:
* **DNA synthesis:** Folate is a crucial cofactor in the synthesis of purines and pyrimidines, the building blocks of DNA.
* **DNA repair:** Folate participates in the repair of damaged DNA, preventing mutations and cell damage.
* **Homocysteine metabolism:** Folate is involved in converting homocysteine to methionine, a crucial amino acid.
* **Cell growth and development:** Folate plays a crucial role in cell division and growth, especially during embryonic development.
Therefore, folate transmembrane transport is a vital process for maintaining cellular health and preventing various diseases.'
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Proteins (3)
| Protein | Definition | Taxonomy |
|---|---|---|
| Proton-coupled folate transporter | A proton-coupled folate transporter that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q96NT5] | Homo sapiens (human) |
| Reduced folate transporter | A reduced folate transporter that is encoded in the genome of human. [PRO:DNx, UniProtKB:P41440] | Homo sapiens (human) |
| Multidrug resistance-associated protein 5 | An ATP-binding cassette sub-family C member 5 that is encoded in the genome of human. [PRO:DNx, UniProtKB:O15440] | Homo sapiens (human) |
Compounds (11)
| 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 |
| sulfinpyrazone | Sulfinpyrazone: A uricosuric drug that is used to reduce the serum urate levels in gout therapy. It lacks anti-inflammatory, analgesic, and diuretic properties. | pyrazolidines; sulfoxide | uricosuric drug |
| trequinsin | trequinsin: RN given refers to parent cpd; structure given in first source | pyridopyrimidine | |
| methotrexate | dicarboxylic acid; monocarboxylic acid amide; pteridines | abortifacient; antimetabolite; antineoplastic agent; antirheumatic drug; dermatologic drug; DNA synthesis inhibitor; EC 1.5.1.3 (dihydrofolate reductase) inhibitor; immunosuppressive agent | |
| 10-propargyl-10-deazaaminopterin | 10-propargyl-10-deazaaminopterin: structure in first source pralatrexate : A pteridine that is the N-4-[1-(2,4-diaminopteridin-6-yl)pent-4-yn-2-yl]benzoyl derivative of L-glutamic acid. Used for treatment of Peripheral T-Cell Lymphoma, an aggressive form of non-Hodgkins lymphoma. | N-acyl-L-glutamic acid; pteridines; terminal acetylenic compound | antimetabolite; antineoplastic agent; EC 1.5.1.3 (dihydrofolate reductase) inhibitor |
| l 660,711 | quinolines | ||
| cyclic gmp | 3',5'-cyclic GMP : A 3',5'-cyclic purine nucleotide in which the purine nucleobase is specified as guanidine. Cyclic GMP: Guanosine cyclic 3',5'-(hydrogen phosphate). A guanine nucleotide containing one phosphate group which is esterified to the sugar moiety in both the 3'- and 5'-positions. It is a cellular regulatory agent and has been described as a second messenger. Its levels increase in response to a variety of hormones, including acetylcholine, insulin, and oxytocin and it has been found to activate specific protein kinases. (From Merck Index, 11th ed) | 3',5'-cyclic purine nucleotide; guanyl ribonucleotide | Escherichia coli metabolite; human metabolite; mouse metabolite; plant metabolite; Saccharomyces cerevisiae metabolite |
| sildenafil | sildenafil : A pyrazolo[4,3-d]pyrimidin-7-one having a methyl substituent at the 1-position, a propyl substituent at the 3-position and a 2-ethoxy-5-[(4-methylpiperazin-1-yl)sulfonyl]phenyl group at the 5-position. | piperazines; pyrazolopyrimidine; sulfonamide | EC 3.1.4.35 (3',5'-cyclic-GMP phosphodiesterase) inhibitor; vasodilator agent |
| raltitrexed | N-acyl-amino acid | ||
| pemetrexed | pemetrexed disodium : An organic sodium salt that is the disodium salt of N-{4-[2-(2-amino-4-oxo-4,7-dihydro-1H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl}-L-glutamic acid. Inhibits thymidylate synthase (TS), 421 dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyltransferase (GARFT). | N-acyl-L-glutamic acid; pyrrolopyrimidine | antimetabolite; antineoplastic agent; EC 1.5.1.3 (dihydrofolate reductase) inhibitor; EC 2.1.1.45 (thymidylate synthase) inhibitor; EC 2.1.2.2 (phosphoribosylglycinamide formyltransferase) inhibitor |