Intestinal Absorption Of Riboflavin Research Articles

Functional Characteristics of the Human Ortholog of Riboflavin Transporter 2 and Riboflavin-Responsive Expression of Its Rat Ortholog in the Small Intestine Indicate Its Involvement in Riboflavin Absorption , ,

Riboflavin transporter (RFT) 2 has recently been identified as a transporter that may be, mainly based on the functional characteristics of its rat ortholog (rRFT2), involved in the intestinal absorption of riboflavin. The present study was conducted to further examine such a possible role of RFT2, focusing on the functional characteristics of its human ortholog (hRFT2) and the response of rRFT2 expression in the small intestine to deprivation of dietary riboflavin. When transiently expressed in human embryonic kidney 293 cells, hRFT2 could transport riboflavin efficiently in a pH-sensitive manner, favoring acidic pH and without requiring Na+. Riboflavin transport by hRFT2 was saturable with a Michaelis constant of 0.77 µmol/L at pH 6.0, and inhibited by some riboflavin derivatives, such as lumiflavin. It was also inhibited, to a lesser extent, by some cationic compounds, such as ethidium. Thus, hRFT2 was suggested to, together with a finding that its mRNA is highly expressed in the small intestine, have characteristics as an intestinal RFT. Furthermore, feeding rats a riboflavin-deficient diet caused an upregulation of the expression of rRFT2 mRNA in the small intestine, presumably as an adaptive response to enhance riboflavin absorption, which would involve rRFT2, and its apically localized characteristic was suggested by the observation of rRFT2 tagged with green fluorescent protein stably expressed in polarized Madin-Darby canine kidney II cells. All these results combined indicate that RFT2 is a transporter involved in the epithelial uptake of riboflavin in the small intestine for its nutritional utilization.

Identification and Functional Characterization of Rat Riboflavin Transporter 2

We have newly identified rat riboflavin transporter 2 (rRFT2) and its human orthologue (hRFT2), and carried out detailed functional characterization of rRFT2. The mRNA of rRFT2 was highly expressed in jejunum and ileum. When transiently expressed in human embryonic kidney (HEK) 293 cells, rRFT2 could transport riboflavin efficiently. Riboflavin transport mediated by rRFT2 was Na(+)-independent but moderately pH-sensitive, being more efficient in acidic conditions than in neutral and basic conditions. Kinetic analysis indicated that rRFT2-mediated riboflavin transport was saturable with a Michaelis constant (K(m)) of 0.21 microM. Furthermore, it was specifically and strongly inhibited by lumiflavin, flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), and to a lesser extent by amiloride. Such ability to transport riboflavin in a specific manner, together with its high expression in the small intestine, indicates that RFT2 may play a role in the intestinal absorption of riboflavin.

Riboflavin absorption in children with biliary obstruction.

The intestinal absorption of riboflavin, a vitamin which is absorbed by a specialized transport process in the proximal small intestine, was studied in nine infants and children with biliary obstruction (mainly due to congenital biliary atresia). After oral administration of a saturation dose of the vitamin (150 mg/sq m), the absorption of riboflavin, as shown by urinary recovery and maximum excretion rate data, was significantly impaired in the patients as compared to normal children of similar ages. Surgical correction of biliary atresia in two patients led to increased absorption of the vitamin.

Effect of Age on Intestinal Absorption of Riboflavin in Humans

The development of gastrointestinal absorption function in humans was studied using riboflavin, a vitamin which is absorbed by a site-specific (proximal small intestine) and saturable transport process. Oral doses of 150 mg./m.2 body surface area of riboflavin-5′-phosphate were administered in solution to subjects ranging in age from 0.25 to 40 years. The urinary recovery of the vitamin increased significantly (from 6 to 12% of the dose) over this age range. The ratio of maximum excretion rate to dose and the time of occurrence of the maximum excretion rate were independent of age. The kinetics of riboflavin elimination also did not show any appreciable change with age. These observations suggest that, in the age range studied, younger subjects retain the vitamin at intestinal absorption sites for a shorter period of time than do older subjects. This appears to be due to decreased intestinal transit rate with increasing age. Prompt release of drugs from pharmaceutical dosage forms seems therefore even more important in children than in adults in order to assure adequate absorption.

Intestinal absorption of riboflavin by man.

Intestinal absorption of riboflavin by man.

Intestinal Absorption of Riboflavin by Rat and Hamster

A number of techniques in vivo and in vitro have provided quantitative data concerning passage of carbohydrates, lipids, and amino acids across the intestinal wall. The water-soluble B-vitamins, aside from B!2 have not been extensively studied by these techniques. We present data here on the absorption in vivo and in vitro of riboflavin by the intestinal tract of rat and hamster, and a correlation of this information with available knowledge of riboflavin metabolism by the intestine.