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Folate transport.
Chemioterapia : International Journal of the Mediterranean Society of Chemotherapy
|October 1, 1985
Summary
Monoglutamyl folates are absorbed by intestinal cells via a genetically determined, energy-dependent carrier system. At high concentrations, passive diffusion also contributes to folate uptake.
Area of Science:
- Gastroenterology
- Nutritional Biochemistry
- Molecular Biology
Background:
- Folate absorption is crucial for human health, with monoglutamyl folates being the primary dietary form.
- The precise mechanisms governing folate uptake in the intestinal epithelium have been a subject of research.
- Understanding folate transport is vital for addressing folate deficiency and optimizing folate therapy.
Purpose of the Study:
- To elucidate the mechanism of monoglutamyl folate uptake by intestinal epithelial cells.
- To characterize the kinetic and regulatory properties of the folate transport system.
- To differentiate between physiological and pharmacological folate uptake pathways.
Main Methods:
- In vitro studies using intestinal epithelial cells from various mammalian species.
- Experiments with isolated intestinal microvillus membrane vesicles.
- Analysis of transport kinetics, including saturation, competition, and pH dependence.
- Assessment of sensitivity to metabolic inhibitors and counter-transport phenomena.
Main Results:
- A genetically coded, structure-specific, and energy-dependent carrier-mediated transport system for monoglutamyl folates was identified.
- This transport system is primarily located in the intestinal microvillus membrane and exhibits optimal activity near pH 6.
- The system demonstrates saturation kinetics, competitive inhibition by other folates and methotrexate, and is sensitive to metabolic inhibitors.
- At physiological folate concentrations (<10 µM), carrier-mediated transport predominates.
- At pharmacological concentrations (>10 µM), folate uptake via passive diffusion becomes significant.
Conclusions:
- Intestinal epithelial cells possess a specialized, carrier-mediated system for absorbing monoglutamyl folates under physiological conditions.
- This transport system is pH-dependent and exhibits characteristics of active transport.
- Folate uptake mechanisms shift from carrier-mediated transport to passive diffusion at high, pharmacologically relevant concentrations.