Expert Reviews in Molecular Medicine

Review Article

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

Rongbao Zhaoa1, Larry H. Matherlya2 and I. David Goldmana1 c1

a1 Departments of Medicine and Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.

a2 Department of Pharmacology and the Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI 48201, USA.


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.


c1 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: