Folic acid is an essential nutrient that is required for one-
carbon biosynthetic processes and for methylation of biomolecules. Deficiency of this
micronutrient leads to disturbances in normal physiology of cell. Chronic
alcoholism is well known to be associated with
folate deficiency, which is due in part to
folate malabsorption. The present study deals with the regulatory mechanisms of
folate uptake in liver during chronic
alcoholism. Male Wistar rats were fed 1 g/kg
body weight/day
ethanol (20 %
solution) orally for 3 months, and the molecular mechanisms of
folate uptake were studied in liver. The characterization of the
folate transport system in liver basolateral membrane (BLM) suggested it to be a carrier mediated and acidic pH dependent, with the major involvement of
proton coupled folate transporter and
folate binding protein in the uptake. The
folate transporters were found to be associated with
lipid raft microdomain of liver BLM. Moreover,
ethanol ingestion decreased the
folate transport by altering the Vmax of
folate transport process and downregulated the expression of
folate transporters in
lipid rafts. The decreased transporter levels were associated with reduced
protein and
mRNA levels of these transporters in liver. The deranged
folate uptake together with reduced
folate transporter levels in
lipid rafts resulted in reduced
folate levels in liver and thereby to its reduced levels in serum of
ethanol-fed rats. The chronic
ethanol ingestion led to decreased
folate uptake in liver, which was associated with the decreased number of transporter molecules in the
lipid rafts that can be ascribed to the reduced synthesis of these transporters.