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Folates and Cobalamins pp 231–245Cite as

Transport of Folate Compounds by Hematopoietic Cells

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Abstract

Hematopoietic cells are unable to synthesize folate de novo and thus have developed efficient transport systems that can retrieve this vitamin from the extracellular environment. The principal source of folate for hematopoietic cells is 5- methyl-H4folate, the major circulating form of folate in mammals. Utilization of 5-methyl-H4folate depends on efficient uptake by membrane-associated transport systems and also on its intracellular conversion to tetrahydrofolate via methionine synthase. Internalized 5-methyl-H4folate is then trapped within the cell by polyglutamylation. Transport system for folate compounds also serve as the primary route by which methotrexate and other antifolate drugs enter hematopoietic cells [12, 41, 50]. In addition, the extent of drug uptake has been correlated in several cases to the overall sensivity of tumor cells to antifolates [44, 53], and resistance to these compounds can occur via alteration in membrane transport [41]. The toxicity of antifolate drugs is also affected by the presence of folate transport systems in normal proliferating cells (e.g., in bone marrow, liver, and the intestinal mucosa) that mediate the efficient uptake of antifolate drugs.

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Authors
  1. G. B. Henderson
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Editors and Affiliations

  1. Division d’Hématologie et d’Oncologie médicale, Hôpital Royal Victoria et Département de Médecine interne et de Physiologie, Université McGill, Montréal, Québec, Canada

    Bernard A. Cooper

  2. Laboratoire d’Hématologie, Hôpital Henri Mondor et Faculté de Médecine, 94010, Créteil, France

    Jacqueline A. Zittoun

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© 1989 Springer-Verlag Berlin Heidelberg

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Henderson, G.B. (1989). Transport of Folate Compounds by Hematopoietic Cells. In: Cooper, B.A., Zittoun, J.A. (eds) Folates and Cobalamins. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-74364-1_19

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  • DOI: https://doi.org/10.1007/978-3-642-74364-1_19

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-50653-9

  • Online ISBN: 978-3-642-74364-1

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