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Membrane transport of folates
Larry H Matherly1, David I Goldman
1Experimental and Clinical Therapeutics Program, Barbara Ann Karmanos Cancer Institute, Department of Pharmacology, Wayne State University School of Medicine, Detroit, Michigan 48201, USA.
Vitamins and Hormones
|July 11, 2003
Summary
Mammalian cells utilize diverse folate transport mechanisms, including carriers and receptors, crucial for nutrient uptake and antifolate drug efficacy. Understanding these transporters aids in cancer treatment.
Area of Science:
- Cellular biology
- Molecular biology
- Biochemistry
Background:
- Folates are essential vitamins crucial for cellular processes.
- Understanding folate transport is vital for cellular metabolism and drug development.
Purpose of the Study:
- To review current knowledge on folate transport mechanisms in mammalian cells.
- To explore the role of folate transporters in development and cancer chemotherapy.
Main Methods:
- Review of existing literature on folate transport systems.
- Analysis of data from genetic studies (homologous deletion) in mice.
- Examination of antifolate drug transport studies.
Main Results:
- Identified multiple folate transport systems: reduced folate carrier (SLC19), organic anion carriers (SLC21), folate receptors (alpha, beta), and export proteins.
- Characterized transport properties including pH dependence and directionality.
- Demonstrated the critical role of folate transporters in antifolate drug activity and resistance.
Conclusions:
- Folate transport is complex, involving diverse carriers and receptors with distinct properties.
- Folate transporter activity significantly impacts the efficacy and resistance of antifolate cancer drugs.
- Further research on folate transporters in patient specimens will advance clinical understanding of drug response.