Folate transport in the central nervous system

Abstract

Methyltetrahydrofolic acid or folic acid was infused intravenously at a constant rate into conscious untreated or methotrexate-pretreated rabbits. After 150 min, at equivalent plasma concentrations, folic acid or methyltetrahydrofolic acid readily entered the cerebrospinal fluid and probably brain by a saturable transport system. In contrast, after intraventricular injections, folic acid but not methyltetrahydrofolic acid was cleared from cerebrospinal fluid to blood by a saturable system. Intraventribular injection of folic acid at concentrations that saturated folic acid clearance from cerebrospinal fluid did not affect the transport of methyltetrahydrofolic acid from blood into cerebrospinal fluid. These results suggest that the transport system for mehtyltetrahydrofolic acid, which is about half-saturated at normal plasma concentrations, helps maintain the cerebrospinal fluid and probably brain methyltetrahydrofolic acid concentrations within relatively narrow limits. Moreover, folic acid, which the brain cannot utilize, is transported from cerebrospinal fluid. A possible locus for the systems that transport folic acid from and methyltetrahydrofolic acid into the cerebrospinal fluid is the choroid plexus.

A Role for the Proton-coupled Folate Transporter (PCFT-SLC46A1) in Folate Receptor-mediated Endocytosis

“…In normal individuals there is a high (2-3-fold) CSF:blood folate gradient consistent with the active transport of folates across the choroid plexus. Studies on transport of folates into the choroid plexus in vivo and in vitro further substantiate a role for this organ in the transport of folates (32)(33)(34). FR␣ and PCFT mRNA are both expressed in choroid plexus (13,35).…”

Cryptococcus neoformans Gene Expression during Experimental Cryptococcal Meningitis

“…Two of these genes encoded enzymes such as a glycine cleavage system protein precursor and glycine-hydroxymethyltransferase involved in the mitochondrial glycine cleavage system which mediates the entry of one-carbon units into folate-dependent pathways (45). Reduced folates are found in higher concentrations in the CSF (32 ng/ml) than in the plasma (6.5 ng/ml) (81). In addition to the importance of glycine in the metabolism of one-carbon fragments, peptides, and nucleotides within the cell, free glycine plays an important role in the mammalian brain as a neurotransmitter and neuromodulator such that disruption of glycine metabolism in the brain leads to a severe neurological disorder (49).…”

Effects of intramuscular injections of folic acid on serum folates, haematological status and growth performance of growing-finishing pigs

“…However, at high concentrations of folates, the transport system is saturated and folates enter the cerebrospinal fluid by diffusion (Spector and Lorenzo, 1975;Ordonez, 1977). Variations in the capacity of saturation of this transport system might explain the inconsistency of folic acid effect on feed intake between Trials 1 and 2.…”