Reduced folate carrier: Tissue distribution and effects of chronic ethanolintake in the micropig

Background: Folate deficiency is common in alcoholic patients, in part due to abnormal transport across membranes relevant to folate homeostasis. The reduced folate carrier (RFC) transports monoglutamyl folates across tissue membranes and could be affected by chronic exposure to ethanol. The micropi g model is suitable to study the effect of alcoholism on RFC and folate tra nsport across membranes. Methods: The membrane transport of [H-3]-folic acid was measured by a vacuu m filtration method in jejunal brush border (JBB), liver plasma membrane (L PM), and kidney brush border (KBB) membranes vesicles from micropigs fed co ntrol or 40% ethanol diets for 12 months. RFC transcripts were analyzed by reverse transcription polymerase chain reaction in jejunal mucosa, liver, a nd kidney from the same animals. Results: When we compared results from three relevant membranes in control animals, the transport of [H-3]-folic acid was highest in LPM, 3-fold lower in KBB (p < 0.001), and B-fold lower in JBB (p < 0.001). The concentration of RFC transcripts per total RNA was greatest in liver, followed by kidney and jejunum. The transport of [H-3]-folic acid by JBB vesicles from chroni c ethanol-fed animals exhibited 2-fold lower K-m and V-max (p < 0.05), wher eas there was no ethanol effect on the V-max of [H-3]-folic acid transport by LPM or KBB. RFC transcript levels were 10-fold lower in jejunal mucosa f rom ethanol-fed animals than in control-fed animals (p < 0.005). Conclusions: Although our findings demonstrate different RFC transcript amo unts and transport efficiencies among tissues, the present studies suggest that chronic ethanol exposure decreases the intestinal absorption of folic acid by altering the expression of RFC and consequently its transport kinet ics in JBB. These findings provide a mechanism for the clinical finding of reduced folic acid absorption in chronic alcoholics.