Substances with an antithiamin activity are fairly common in nature. They include structurally similar antagonists and structure-altering antagonists. The synthetic compounds pyrithiamin, oxythiamin and amprolium are structurally similar antagonists whose mode of action is competitive inhibition; thus, they interfere with thiamin at different points in metabolism. Pyrithiamin blocks chiefly the esterification of thiamin with phosphoric acid, resulting in inhibition of the thiamin coenzyme cocarboxylase. Oxythiamin likewise displaces cocarboxylase from important metabolic reactions. Amprolium inhibits the absorption of thiamin from the intestine and also blocks the phosphorylation of the vitamin (McDowell, 2000).
Thiaminase activity destroys thiamin by altering the structure of the vitamin. The disease Chastek paralysis in foxes and other animals fed certain types of raw fish results from a thiaminase that splits the thiamin molecule into two components and thus renders it inactive. Since thiaminase is heat labile, the problem can be avoided by cooking the fish at 83°C for at least five minutes. Certain microorganisms (bacteria and molds) and plants (bracken fern) have been shown to produce thiaminases.
Thiamin appears to be readily digested and released from natural sources. A precondition for normal absorption of thiamin is sufficient production of stomach hydrochloric acid. Phosphoric acid esters of thiamin are split in the intestine. Free thiamin is soluble in water and is easily absorbed, especially in the duodenum. The mechanism of thiamin absorption is not yet fully understood, but apparently both active transport and simple diffusion are involved (Braunlich and Zintzen, 1976). At low concentrations there is an active sodium-dependent transport against the electrochemical potential, whereas at high concentrations thiamin diffuses passively through the intestinal wall. Absorbed thiamin is transported via the portal vein to the liver with a carrier plasma protein.
Thiamin phosphorylation can take place in most tissues, but particularly in the liver. Four-fifths of thiamin in animals is phosphorylated in liver under the action of ATP to form the metabolically active enzyme form, thiamin pyrophosphate (TPP, or cocarboxylase). Of total body thiamin, about 80% is TPP, about 10% is thiamin triphosphate (TTP), and the remainder is thiamin monophosphate (TMP) and free thiamin.
Although thiamin is readily absorbed and transported to cells throughout the body, it is not stored to any great extent. Thiamin content in individual organs varies considerably, with the vitamin preferentially retained in organs with a high metabolic activity. During deficiencies, thiamin is retained in greatest quantities in important organs, such as heart, brain, liver and kidney. Intakes in excess of current needs are rapidly excreted. This means that the body needs a regular supply and also that unneeded intakes are excreted. The pig is somewhat of an exception, however. For some unknown reason its tissues contain several times as much thiamin as is the case with other species studied, and thus it has a store that can meet body needs on a thiamin deficient diet for as long as two months (Heinemann et al., 1946).
Absorbed thiamin is excreted in both urine and feces, with small quantities excreted in sweat. Fecal thiamin may originate from feed, synthesis by microorganisms, or endogenous synthesis (i.e., via bile or excretion through the mucosa of the large intestine). When thiamin is administered in large doses, urinary excretion first increases, then reaches a saturation level, and with additional thiamin the fecal concentration increases considerably (Braunlich and Zintzen, 1976). Roth-Maier and Kirchgessner (1993, 1994) determined in two separate investigations that more than 90% to 95% of excess thiamin is excreted via feces.
