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Membrane transporters and folate homeostasis: intestinal absorption and transport into systemic compartments and tissues

Published online by Cambridge University Press:  28 January 2009

Rongbao Zhao ,
Larry H. Matherly  and
I. David Goldman
Rongbao Zhao
Affiliation:
Departments of Medicine and Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Larry H. Matherly
Affiliation:
Department of Pharmacology and the Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI 48201, USA.
I. David Goldman*
Affiliation:
Departments of Medicine and Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
*
*Corresponding author: I. David Goldman, Cancer Center, Albert Einstein College of Medicine, Chanin Two, 1300 Morris Park Avenue, Bronx, NY 10461, USA. Tel: +1 718 430 2302; Fax: +1 718 430 8550; E-mail: [email protected]
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Abstract

Members of the family of B9 vitamins are commonly known as folates. They are derived entirely from dietary sources and are key one-carbon donors required for de novo nucleotide and methionine synthesis. These highly hydrophilic molecules use several genetically distinct and functionally diverse transport systems to enter cells: the reduced folate carrier, the proton-coupled folate transporter and the folate receptors. Each plays a unique role in mediating folate transport across epithelia and into systemic tissues. The mechanism of intestinal folate absorption was recently uncovered, revealing the genetic basis for the autosomal recessive disorder hereditary folate malabsorption, which results from loss-of-function mutations in the proton-coupled folate transporter gene. It is therefore now possible to piece together how these folate transporters contribute, both individually and collectively, to folate homeostasis in humans. This review focuses on the physiological roles of the major folate transporters, with a brief consideration of their impact on the pharmacological activities of antifolates.

Type
Review Article
Information
Expert Reviews in Molecular Medicine , Volume 11 , July 2009 , e4
Copyright
Copyright © Cambridge University Press 2009

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References

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Further reading, resources and contacts

For an in-depth up-to-date review of hereditary folate malabsorption from the clinical and genetic perspectives see:

Matherly, L.H., Hou, Z. and Deng, Y. (2007) Human reduced folate carrier: translation of basic biology to cancer etiology and therapy. Cancer and Metastasis Reviews 26, 111-128Google Scholar
Salazar, M.D. and Ratnam, M. (2007) The folate receptor: what does it promise in tissue-targeted therapeutics? Cancer and Metastasis Reviews 26, 141-152Google Scholar
Chattopadhyay, S., Moran, R.G. and Goldman, I.D. (2007) Pemetrexed: biochemical and cellular pharmacology, mechanisms, and clinical applications. Molecular Cancer Therapeutics 6, 404-417Google Scholar
Geller, J. et al. (2002) Hereditary folate malabsorption: family report and review of the literature. Medicine 81, 51-68Google Scholar
http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=folate-malGoogle Scholar
http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=folate-malGoogle Scholar