methotrexate transmembrane transporter activity

Definition

Target type: molecularfunction

Enables the transfer of methotrexate, 4-amino-10-methylformic acid from one side of a membrane to the other. Methotrexate is a folic acid analogue and a potent competitive inhibitor of dihydrofolate reductase. [GOC:ai]

Methotrexate transmembrane transporter activity refers to the process by which cells move the drug methotrexate across their plasma membrane. This activity is crucial for the therapeutic efficacy of methotrexate, a widely used chemotherapy drug. Methotrexate is an analog of dihydrofolate, a key cofactor in the synthesis of purines and thymidine, essential building blocks for DNA and RNA. By inhibiting dihydrofolate reductase, the enzyme that converts dihydrofolate to tetrahydrofolate, methotrexate effectively blocks DNA and RNA synthesis, ultimately leading to cell death.

To reach its target, methotrexate must first enter the cell. This is achieved through a complex interplay of various transmembrane transporter proteins, which facilitate the movement of molecules across the cell membrane. Methotrexate transmembrane transporter activity is particularly important for the accumulation of methotrexate within target cells, such as rapidly dividing cancer cells.

The specific transporter proteins responsible for methotrexate uptake vary depending on the cell type and the specific tissue. Some of the key transporters involved include:

1. **Reduced folate carrier (RFC1):** This is the primary transporter responsible for methotrexate uptake in many cell types, including those in the liver, kidney, and intestines. RFC1 is a membrane-bound protein that utilizes the electrochemical gradient across the membrane to drive methotrexate transport.

2. **Human equilibrative nucleoside transporter 1 (hENT1):** This transporter is also involved in methotrexate uptake in certain cell types, including hematopoietic cells. hENT1 is a bidirectional transporter, meaning it can transport methotrexate both into and out of the cell.

3. **Organic anion transporting polypeptides (OATPs):** These transporters, particularly OATP1B1 and OATP1B3, play a role in methotrexate uptake in the liver and other tissues. OATPs facilitate the uptake of a wide range of organic anions, including methotrexate.

The activity of these transporters can be influenced by various factors, including:

* **Genetic variations:** Polymorphisms in the genes encoding these transporters can alter their expression and function, potentially affecting methotrexate sensitivity and efficacy.
* **Drug-drug interactions:** Other drugs can compete with methotrexate for binding to these transporters, potentially reducing its uptake into cells.
* **Physiological factors:** Factors such as age, gender, and nutritional status can also influence transporter activity.

Understanding the molecular function of methotrexate transmembrane transporter activity is crucial for optimizing methotrexate therapy. By considering the role of these transporters in methotrexate uptake and distribution, clinicians can better tailor treatment strategies to individual patients, maximizing therapeutic efficacy and minimizing potential adverse effects.'
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Proteins (2)

Compounds (4)