Thiamine chemical structure

Figure 1 shows the chemical structure ofvitamin B1 or thiamin (3-(4-amino-2-methyl-pyrimidin-5-ylmethyl)-5-(2-hydroxyethyl)-4-methylthiazolium) and its coenzyme form thiaminpyrophosphate (TPP). 

Application of Global Sequence Similarity to Find an Inhibitor of Acetolactate Synthase. Acetolactate synthase (ALS) Is the site of action of sulfonylurea, Imldazollnone, and trlazolo pyrimidine herbicides (10-14). Their mode of Inhibition and binding sites on ALS were ambiguous, because (1) these herbicides bear no obvious similarity In their chemical structures to those of ALS substrates (pyruvate and acetolactate), cofactors (thiamine pyrophosphate, FAD, and Mg ) and effectors (valine, Isoleuclne, and leucine) and (2) they Inhibit ALS In a mode too complex to be analyzed. 

With respect to the chemical structure, it was clarified that a sulfur atom was present [14]. It was Dr Katashi Makino, a physician of the South Manchuria Railway Hospital (Dairen, Manchuria, the Great Empire of Japan), who suggested that the pyrimidine ring and the thiazole ring were combined through a methylene moiety [15]. The chemical structure of vitamin Bj hydrochloride (thiamin hydrochloride) was also supported by other researchers [16], and the structure was established by chemical synthesis [17]. As described in Chapter 11 (Section 11.1), Dr Makino also provided the first correct chemical structure of ATP. 

Chemical structure (Figure 6). Pyrimidine and thiazole moiety linked by methylene bridge - phos-phorylated forms thiamine monophosphate (TMP), thiamine diphosphate (TDP), thiamine triphosphate (TTP). 

The thermal generation of flavor is a very essential process for the "taste" of many different foodstuffs, e.g. cocoa, coffee, bread, meat. The resulting aromas are formed through non-enzymatic reactions mainly with carbohydrates, lipids, amino acids (proteins), and vitamins under the influence of heat. Thiamin (vitamin B ) and the amino acids, cysteine and methionine, belong to those food constituents which act as flavor precursors in thermal reactions. The role of thiamin as a potent flavor precursor is related to its chemical structure which consists of a thiazole as well as a pyrimidine moiety. The thermal degradation of this heterocyclic constituent leads to very reactive intermediates which are able to react directly to highly odoriferous flavor compounds or with degradation products of amino acids or carbohydrates. 

The chemical structure of thiamine is shown in Figure LA pyrimidine moiety (2-methyl-4-amino-5-hydroxymethylpyrimidine) and a thiazole moiety (4-methyl-5-hydroxyethylthiazole) are connected by a methylene group. The double-salt form of thiamine with hydrochloric acid (C12H17N4OSCI-HCI molecular weight 337.28) is readily soluble in water, less soluble in methanol and glycerol, nearly insoluble in ethanol, and insoluble in ether and benzene (1). 

According to Lowe and Ingraham (301), it is very likely that thiamine-PP must have optimized, through chemical adaptation, its chemical structure... 

Thiamine Vitamin Bi) is one of the longest-known vitamins. Its chemical structure is somewhat complicated it contains two heterocyclic rings (a pyrimidine and a thiazol ring, formula in Chapt. VI-5) connected at a quaternary N atom. It can easily be converted to the dihydro form, but its catalytic function does not seem to be that of a redox sy.stem. Thiamine pyrophosphate is the coenzyme of decarboxylases and aldehyde transferases. It plays a key role in oxidative decarboxylation of pyruvate (in the breakdown of carbohydrate) and of a-keto glutarate (in the citrate cycle). Man s requirements of thiamine are calculated in conjunction with his caloric intake, since the demand for the coenzyme is apparently higher wth a high overall metabolic rate. 

FIGURE 3.7 Chemical structure of B-vitamins found in cereal grains, (a) Thiamine, (b) Riboflavin, (c) Pyridoxine. (d) Niacin, (e) Folic acid. 

The recognition of their structure permits the determination of vitamins by the tools of analytical chemistry, but while such methods are widely used in industrial production, the minute quantities in body fluids and tissues limit the purely chemical approach to a few members of this group present in relatively high concentration, e.g., vitamin C (K5). Microchemical methods are in use for the determination of thiamine, riboflavin, and some of the fat-soluble vitamins, based on the most sensitive colorimetric and, in particular, fluorometric techniques. Vitamin D, on the other hand, is determined by animal assay. 

Food processing operations can be optimized according lo the principles used for other chemical processes if the composition, Ihernio-phvsical properties, and structure of the food is known, However, the complex chemical composition and physical structures of most foods can make process optimization difficult. Moreover, the quality of a processed product may depend more on consumer sensory responses than on measurable chemical or physical attributes. Retention levels of ascorbic acid. CoHnO. or thiamine can often be used as an indicator of process conditions. 

An X-ray structure of a thiamine dependent transketolase enzyme was determined by Schneider et al. after isolation from Saccharomyces cerevisiae in the 1990s and is shown in Fig. 10 (Sundstrom et al. 1993 Nilsson et al. 1997). The thiamine cofactor is embedded in a narrow channel in the centre of the enzyme. From the complex surrounding of the heart of this enzyme it seems to be obvious that chemical reactions at the catalytically active site in this channel proceed inevitably with high selectivities. 

However, another study was an example of nature appreciation—the structure of thiamine was varied to learn what was special about the particular thiazolium derivative that was natural thiamine (11). As a chemical catalyst—ignoring the question of what effect changes would have on the ability of the coenzyme to bind to the proteins that have evolved to use it—thiamine proved to be the optimal relative to other related structures because of a balance of catalytic ability and chemical stability. The anion 4 derived from an imidazolium ring instead of a thiazolium ring was a weaker catalyst but was more stable in water (10). [The imidazolium aiuon and its dihydro derivative have proven to be very useful metal ion ligands, including... 

Most vitamins function either as a hormone/ chemical messenger (cholecalciferol), structural component in some metabolic process (pantothenic acid), or a coenzyme (phytonadi-one, thiamine, riboflavin, niacin, pyridoxine, biotin, folic acid, cyanocobalamin). At least one vitamin has more than one biochemical role. Vitamin A as an aldehyde (retinal) is a structural component of the visual pigment rhodopsin and, in its acid form (retinoic acid), is a regulator of cell differentiation. The precise biochemical functions of ascorbic acid and a-tocopherol still are not well defined. 

C. B. Rios, Generation, Structure and Chemical Properties of Enamines Related to the Key Intermediate in Thiamin Diphosphate Dependent Enzymatic Pathways. Ph.D. Thesis, Rutgers University Graduate Eaculty at Newark, NJ, 1988. 

Only oxazole, of the trio, does not play any part in normal biochemical processes, though there are secondary metabolites (especially from marine organisms) which incorporate thiazole (and oxazole) units - the antibiotic cystothiazole A, from the myxobacterium Cyctobacter fuscus is an example. Imidazole occurs in the essential amino acid histidine histidines within enzymes are intimately involved in catalysis requiring proton transfers. The structurally related hormone, histamine, is a vasodilator and a major factor in allergic reactions such as hay fever. The thiazolium ring is the chemically active centre in the coenzyme derived from thiamin (vitamin B,). 

Structural formula of thiamin and its chemical properties. (A) Structural formula of thiamin. (B) The C-2 carbon of the thiazolium moiety can lose its proton yielding a highly nucleophilic ylide analogous to cyanide. (C) Cyanide and thiamin catalysed condensation of benzaldehyde to benzoin. (D) Oxydation of thiamin in strongly alkaline medium yields the highly fluorescent thiochrome, a property used for the experimental determination of thiamin and its phosphate esters. 

Most physiologically active compounds owe their biological properties to the presence of heteroatoms, mainly in the form of heterocydes. A majority of the known natural products are heterocyclic. It is therefore not surprising that more than half the published chemical literature deals with such compounds—then-synthesis, isolation, and interconversions. Indeed, we have already encountered many examples—the cyclic ethers (Section 9-6), acetals (Sections 17-8, 23-4, and 24-8), carboxylic acid derivatives (Chapters 19 and 20), and amines (Chapter 21). The bases in DNA, whose sequence stores hereditary information, are heterocydes (Section 26-9) so are many vitamins, such as Bi (thiamine. Real Life 23-2), B2 (riboflavin. Real Life 25-3), Bg (pyridoxine), the spectacularly complex B12, and vitamins C and E (Section 22-9). The structures of vitamins Bg and B12, as well as additional examples of heterocyclic systems and their varied uses, are depicted here. 

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