Thiamin thiol form

The yellow form (11) on acidification is converted to the more stable thiol form (12). On oxidation, typically with alkaline ferhcyanide, yellow form (11) is irreversibly converted to thiochrome [299-35-4] (14), a yellow crystalline compound found naturally in yeast but with no thiamine activity. In solution, thiochrome exhibits an intense blue fluorescence, a property used for the quantitative determination of thiamine. 

The thiol form (12) is susceptible to oxidation (see Fig. 2). Iodine treatment regenerates thiamine in good yield. Heating an aqueous solution at pH 8 in air gives rise to thiamine disulfide [67-16-3] (21), thiochrome (14), and other products (22). The disulfide is readily reduced to thiamine in vivo and is as biologically active. Other mixed disulfides, of interest as fat-soluble forms, are formed from thiamine, possibly via oxidative coupling to the thiol form (12). 

The weakly basic portion of thiamin or of its coenzyme forms is protonated at low pH, largely on N-l of the pyrimidine ring. 86 88 The pKa value is 4.9. In basic solution, thiamin reacts in two steps with an opening of the thiazole ring (Eq. 14-15) to give the anion of a thiol form which may be crystallized as the sodium salt.79 84 This reaction, like the competing reaction described in Eq. 7-19, and which leads to a yellow... 

Thiamin is unstable at high pH90 91 and is destroyed by the cooking of foods under mildly basic conditions. The thiol form undergoes hydrolysis and oxidation by air to a disulfide. The tricyclic form (Eq. 7-19) is oxidized to thiochrome, a fluorescent compound... 

A small amount of thiamin is excreted in the urine unchanged, accounting for about 3% of a test dose, together with small amounts of thiamin monophosphate and thiamin diphosphate. As discussed in Section 6.5.1, this can be used to assess thiamin nutritional status. One of the major excretory products is thiochrome cyclization to thiochrome is the basis of the normal method of determining thiamin so, most reports of thiamin excretion are actually of thiamin plus thiochrome. In addition, small amounts of thiamin disulfide, formed by the oxidation of thiamin thiol, are also excreted. 

The thiol form (12) undergoes reactions mainly via its /V-formyl or ene—thiol groups. Heating an aqueous solution of the thiol form (Fig. 2) effects hydrolysis to the diamine 4-amino-5-aminomethyl-2-methyl-pyrimidine [95-02-3] (16), 5-hydroxy-3-mercaptopentan-2-one [15678-01 -0] (17), and formic acid (20). Neutralization of a solution of the thiolate anion with carbon dioxide gives a fat-soluble basic material [21682-72-4, 35922-43-1] (20), presumably via dihydrothiochrome (10) (21). Acylation of the thiolate occurs on both sulfur and oxygen to give mono- or diacyl thiamines, some of which are interesting fat-soluble depot forms of thiamine. 

Diphosphothiamine disulfide isolated from yeast is probably formed from the thiol form of thiamine diphosphate which in aqueous solution is in equilibrium with the ammonium form (Fig. 185). As yet it is not clear whether diphospho-thiamine disulfide possesses any physiological importance. 

In some instances, the reactive forms or the intermediates themselves, show polarographic waves which are separated from those of reactants and products. The formation of the thiol form of thiamine, < ) the bicyclic form of protopine< > and the enediol forms of some sugars< > and pyridoine< ) are examples of the formation and detection of reactive forms. A few examples of the detection of intermediates, are the diketone and enediol produced during the alkaline degradation of phenylglyoxal< > and of a, -unsaturated ketone as an intermediate in the cleavage< ) of... 

Karrer and Viscontini have found that the thiol form of TPP is as active as TPP in the yeast carboxylase assay. Evidence for the open-ring form of thiamine in nature also is at hand. Approximately 50% of the thiamine in milk has long been known to be present in a form which is released only upon treatment with a proper proteolytic enzyme. In the light of present-day knowledge this bound form is suggestive of a thiamine-protein-S-S complex or of lipothiamide. Bonvicino and Hennessey have prepared a complex of the former type and found it to be biologically active to the extent of 90 %. Myrback and his co-workers have evidence to the effect that well-aerated baker s yeast contains what is probably the disulfide form of TPP. 

A number of enzymes have been reported which decompose thiamine without separating the two ring moieties. Thus garlic and certain other plants possess an enz nne which catalyzes formation of a disulfide from thiamine and allicin [Eq. (8)]. Presumably thiamine reacts in the thiol form (Se, S7). 

As far as 2-methyl-3-furanthiol is concerned, it can be formed from cysteine, but thiamine constitutes its more important precursor by far.256 When the reaction is carried out in the presence of thiamine in an aqueous medium at 120 °C for 1 h, only about 8% of the thiol is derived from cysteine, and, in the absence of thiamine from the mix, no thiol was detected. The probable mechanism of formation from thiamine is shown in Scheme 5.16.257... 

But this thiol ester is not formed by the expected mechanism in the enzymatic reaction. Thiamine delivers a nucleophilic acetyl group to an c/ectrophilic sulfur atom—the reverse polarity to normal ester formation. 

The investigation of characteristic flavors associated with cooked meats has been the subject of much research over the past four decades but, although compounds with "meaty" aromas had been synthesized, compounds with such characteristics were not found in cooked meats until recently (1). In the search for compounds with characteristic aromas it was found that furans and thiophenes with a thiol group in the 3-position possessed meat-like aromas (2). The corresponding disulfides formed by oxidation of furan and thiophene thiols were also found to have meat-like characteristics, and exceptionally low odor threshold values (3). A number of such compounds are formed in heated model systems containing hydrogen sulfide or cysteine and pentoses or other sources of carbonyl compounds (4,5), The thermal degradation of thiamine also produces 2-methyl-3-fiiranthiol and a number of sulfides and disulfides (6J). 

The mechanism of action of cocarboxylase is still very obscure. The suggestion has been offered that the thiol and disulfide forms of thiamine might constitute an oxidation-reduction system. Subsequently, it has been shown in enzyme experiments with yeast that the isomeric thiazole pyrophosphate exhibited full cocarboxylase activity, whereas the disulfide... 

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