Figure 6.
Folate-specific transport routes in mammalian cells. There are two carrier mechanisms: the reduced folate carrier (RFC), an organic phosphate (OP−) antiporter, and the proton-coupled folate transporter (PCFT), a proton-folate symporter. Both carriers transport folates and antifolates into cells against an electrochemical-potential gradient. Multidrug resistance-associated proteins (MRPs) and the breast cancer resistance protein (BCRP) utilize the energy released in the hydrolysis of ATP to pump folate and antifolate monoglutamates out of cells. BCRP and some MRPs can export lower polyglutamates as well. Folate receptors transport folates into cells by an endocytic mechanism. Folate export from acidified endosomes is mediated, in part, by PCFT.