THIAMINE UPTAKE IN HUMAN INTESTINAL BIOPSY SPECIMENS, INCLUDING OBSERVATIONS FROM A PATIENT WITH ACUTE THIAMINE-DEFICIENCY

Mucosal biopsy specimens obtained by routine endoscopy from 108 human subjects, including one patient with thiamine deficiency, were incubat ed at 37 degrees C in oxygenated calcium-free Krebs-Ringer solution (p H 7.5) containing tritiated thiamine and [C-14]dextran as a marker of adherent mucosal water. The amount of labeled thiamine taken up was me asured radiometrically. In subjects with no clinical evidence of thiam ine deficiency, 1) thiamine uptake by duodenal mucosa had a hyperbolic time course, reaching equilibrium at 10 min; 2) thiamine concentratio ns < 2.5 mu mol were taken up predominantly by a saturable mechanism d isplaying Michaelis-Menten kinetics (K-m 4.4 mu mol/L and J(max) 2.3 p mol.mg wet tissue(-1).6 min(-1)), whereas higher concentrations were t aken up by passive diffusion; 3) thiamine transport had different Capa cities along the gastrointestinal tract (duodenum much greater than co lon > stomach); and 4) thiamine uptake was competitively inhibited in the duodenum by thiamine analogs, albeit with a different order of pot ency compared with rats, and was blocked by 2,4-dinitrophenol. In the thiamine-deficient patient, the duodenal saturable uptake was increase d, with higher K-m and J(max) values. In conclusion, physiologic conce ntrations of thiamine were transported in human small intestine by a s pecific mechanism dependent on cellular metabolism, whose transporters appear to be down-regulated.