Low Folate Transport Across Intestinal Basolateral Surface is Associated with Down-regulation of Reduced Folate Carrier in In Vivo Model of Folate Malabsorption

The process of folate transport regulation across biological membranes is of considerable interest because of its ultimate role in providing one-carbon moieties for key cellular metabolic reactions and exogenous requirement of the vitamin in mammals. Although, intestinal folate malabsorption is established phenomena in alcoholism; however, there is no knowledge regarding the mechanism of folate exit across intestinal basolateral membrane (BLM) to circulation during alcohol associated malabsorption. In the present study, male Wistar rats were fed 1 g/kg body weight/day ethanol (20% solution) orally for 3 months and regulatory characteristics of folate transport at BLM surface were evaluated. The folate transport was found to be carrier mediated, saturable, with pH optima at 7.0, besides exhibiting Na+ independence. The chronic alcohol ingestion resulted in alteration of transport kinetics, shifting the process to K+ dependent one besides affecting the status of S-S linkage of the transport system. Importantly, chronic ethanol ingestion reduced the folate exit across the BLM by decreasing the affinity of transporter (high K-m) for substrate and by decreasing the number of transporter molecules (low V-max) on the surface. The decreased basolateral transport activity was associated with down-regulation of the reduced folate carrier (RFC) which resulted in decreased RFC protein levels in BLM in rat model of alcoholism. The study suggests that during alcohol ingestion, RFC mediated deregulated folate transport across BLM also attributes to folate malabsorption.