Thiamin Vitamers and Antagonists

Synthetic cdlithiamin derivatives, such as thieimin propyl and tetreihydro-furfuryl disulfides, have been used for the prevention emd treatment of thitunin deficiency. Because they are lipid soluble, and are not subject to the normtd control of thiamin absorption by saturation of the intestinal transport system, they have potenticd benefits in the treatment of thitunin-deficient tdcoholics, whose absorption of thieimin is impeured. 

Thiamin is labile to sulfite, which cleaves the methylene bridge. The reaction is slow at acid pH, but rapid above pH 6. Sulfite treatment of dried fruit emd other foods results in more or less complete loss of thiamin. 

Two tmalogs of thiamin, oxythiamin emd pyrithiamin, are potent em-timetaboUtes emd have been widely used to induce thitunin deficiency in ex-perimenttd tuiimtils. The mechanisms of action of pyrithicimin, oxythiamin, tmd thiamintises found in foods me discussed in Section 6.4.7. 

The free base is unstable, and two derivatives of thiamin are commonly used in food enrichment and pharmaceutical preparations thiamin chloride hydrochloride (generally known simply as thiaminhydrochloride) and thiamin mononitrate. The mononitrate is less hygroscopic than the chloride hydrochloride and is the preferred form for food enrichment. There is considerable difficulty in interpreting much of the literature on thiamin requirements, because many authors quote mg of thiamin, without specifying whether it was as the free base, the chloride hydrochloride, or the equivalent amount of free base. Because the Mr of free thiamin is 266.4, and that of the chloride hydrochloride is 337.3, this confusion can result in errors of the order of 26%. 

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Over 250 analogues of the B vitamers have been reported (11,100). Nearly all have low vitamin B activity and some show antagonism. Among these are the 4-deshydroxy analogue, pyridoxine 4-ethers, and 4-amino-5-hydroxymeth5i-2-methyipyrimidine, a biosynthetic precursor to thiamine. StmcturaHy unrelated antagonists include dmgs such as isoniazid, cycloserine, and penicillamine, which are known to bind to pyridoxal enzyme active sites (4). 

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