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Review Article

Thiamine Intestinal Transport and Related Issues: Recent Aspects

Institute of Human Physiology, University of Pavia, Pavia, Italy

In the intestinal lumen thiamine is in free form and very low concentrations. Absorption takes place primarily in the proximal part of the small intestine by means of a dual mechanism, which is saturable at low (physiological) concentrations and diffusive at higher. Thiamine undergoes intracellular phosphorylation mainly to thiamine pyrophosphate, while at the serosal side only free thiamine is present. Thiamine uptake is enhanced by thiamine deficiency, and reduced by thyroid hormone and diabetes. The entry of thiamine into the enterocyte, as evaluated in brush border membrane vesicles of rat small intestine in the absence of H⁺ gradient, is Na⁺- and biotransformation-independent, completely inhibited by thiamine analogs and reduced by ethanol administration and aging. The transport involves a saturable mechanism at low concentrations of vitamin and simple diffusion at higher. Outwardly oriented H⁺ gradients enhance thiamine transport, whose saturable component is a Na⁺-independent electroneutral uphill process utilizing energy supplied by the H⁺ gradient, and involving a thiamine/ H⁺ 1:1 stoichiometric exchange. The exit of thiamine from the enterocyte, as evaluated in basolateral membrane vesicles, is Na⁺-dependent, directly coupled to ATP hydrolysis by Na⁺-K⁺-ATPase, and inhibited by thiamine analogs. Transport of thiamine by renal brush border membrane vesicles is similar to the intestinal as far as both H⁺ gradient influence and specificity are concerned. In the erythrocyte thiamine transport is a Na⁺-independent, electroneutral process yet with two components: saturable, prevailing at low thiamine concentrations, and diffusive at higher. The saturable (specific) component is missing in patients of the rare disease known as thiamine-responsive megaloblastic anaemia (TRMA), producing a general disturbance of thiamine transport up to thiamine deficiency. The TRMA gene is located in chromosome 1q23.3. Recently, the thiamine transporter has been cloned: it is a protein of 497 aminoacid residues with high homology with the reduced-folate transporter.

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