Thiamin active forms

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. 

FIGURE 18.17 Thiamine pyrophosphate (TPP), the active form of vitamin is formed by the action of TPP-synthetase. 

The thiamine molecule is the stuff that is in your multivitamin pills. The active form in human physiology is thiamine pyrophosphate, in which a pyrophosphate group is added from ATP. 

Thiamine pyrophosphate is a coenzyme and the active form of vitamin B. It functions as coenzyme in decarboxylation of a-keto acid and in hexose monophosphate shunt. 

Thiamine pyrophosphate (TPP) is the biologically active form of fre vitamin, formed by the transfer of a pyrophosphate group from ATP to thiamine (Figure 28.11). Thiamine pyrophosphate serves as a coen zyme in the formation or degradation of a-ketols by transketolase (Figure 28.12A), and in the oxidative decarboxylation of a-keto adds i (Figure 28.12B). 

Vitamin B1 (thiamine) has the active form, thiamine pyrophosphate. It is a cofactor of enzymes catalyzing the conversion of pyruvate to acetyl CoA, a-ketoglutarate to succinyl CoA, and the transketolase reactions in the pentose phosphate pathway. A deficiency of thiamine causes beriberi, with symptoms of tachycardia, vomiting, and convulsions. In Wernicke-Korsakoff syndrome (most common in alcoholics), individuals suffer from apa thy, loss of memory, and eye movements. There is no known toxicity for this vitamin. 

The mechanism of the cleavage of the pyruvate in Eq. 15-37 is not obvious. Thiamin diphosphate is not involved, and free C02 is not formed. The first identified intermediate is an acetyl-enzyme containing a thioester linkage to a cysteine side chain. This is cleaved by reaction with CoA-SH to give the final product. A clue came when it was found by Knappe and coworkers that the active enzyme, which is rapidly inactivated by oxygen, contains a long-lived free radical.326 Under anaerobic conditions cells convert the inactive form E to the active form Ea by an enzymatic reaction with S-adenosylmethionine and reduced flavodoxin Fd(red) as shown in Eq. 15-38.327-329 A deactivase reverses the process.330... 

The identity of the enzyme(s) involved in the latter reaction has been debated (13). However, the formation of the above hydro-xyketone, in analogy with acetoin, has been conceptualized as the consequence of the condensation of the "active" form of acetaldehyde, that is formed by decarboxylative addition of pyruvate to thiamine pyrophospate, with benzaldehyde.The role of pyruvate, in fact has been established. The same mechanism can be invoked for the reaction of cinnamaldehyde.lt is known that the pyruvate decarboxylase (E.C. 4.1.1.1) accepts as substrates a-oxoacids... 

Vitamins are divided into two major categories. They are fat-soluble (A, D, E and K) and water-soluble vitamins (B-complex and vitamin C). B complex vitamins include thiamine (Bi), riboflavin (B2), pantothenic acid (B3), niacin (B5), pyridoxine (Be), biotin (By), folic acid (B9), and cobalamin (Biy). Inositol, cholic and para-aminobenzoic acid are vitamin-like substances sometimes classified as part of the B complex, but no convincing evidence has been shown so far to be included as vitamins. All the fat-soluble vitamins and some B vitamins exist in multiple forms. The active forms of vitamin A are retinol, retinal and retinoic acid and vitamin D is available as ergocalciferol (D2) and cholecalciferol (D3). The vitamin E family includes four tocopherols and four tocotrienols but a-tocopherol being the most abundant and active form. The multiple forms of vitamins are interconvertible and some are interchangeable. 

Describe briefly the structure of thiamine and its active form. 

Thiamin is rapidly converted to its active form, thiamin pyrophosphate, TPP, in the brain and liver by a specific enzyme, thiamin diphosphotransferase. 

Active form of thiamine, that is thiamine pyrophosphate (TPP) is required for the key reactions catalyzed by Pyruvate dehydrogenase complex and alpha-ketoglutarate dehydrogenase complex (TCA cycle). 

One quality shared by most of the vitamins is their inability to be used in the form in which they are absorbed. Most of the vitamins absorbed from the diet must be converted or modified to the active form. For example, vitamin A, in the form of re tiny I ester, must bo converted to retinoic add to perform some of its functions. Thiamin must be converted to thiamin pyrophosphate to be cocnzymatically active Vitamin K must be reduced to dihydrovitamm K, folate must be poiygiu-tamated, and niacin must be converted to NAD to be active in the cell. 

Coenzymes - Many enzymes require nonprotein coenzymes for catalytic activity.8 These are cosubstrates, and must be constantly reconverted into their active form for catalysis to continue. This is not a problem for growing microorganisms since the normal metabolic processes ensure an adequate supply of coenzymes. However, with purified, or immobilized enzymes, maintaining a sufficient concentration of coenzyme can pose a major problem. Coenzymes are expensive and it is seldom economically feasible to add them in stoichiometric amounts. This is often undesirable for chemical reasons, e.g., the coenzyme may be unstable, or the eventual build-up of high concentrations of its inactive form may Induce displacement of an equilibrium reaction in the opposite direction to that desired.3 It is therefore necessary to use catalytic amounts of coenzymes and to ensure that the active forms are continuously regenerated. Some coenzymes present little or no problem in this regard since they are automatically reformed under the normal aqueous reaction conditions or in the presence of oxygen. These include biotin, pyrldoxal phosphate (PLP), thiamine pyrophosphate, flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD).1 ... 

This vitamin, also called aneurin, is the antiberiberi factor. The active coenzyme form is thiamine pyrophosphate (TPP), or coearboxylase. Thiamine triphosphate (TTP) may be an active form in the central nervous system. Of the thiamine in the body, 10% occurs as TTP, 80% as TPP, and 10% as TMP (thiamine monophosphate) (Figure 38-12). 

D. This patient has exhibited symptoms of beri beri heart disease, which is a result of a nutritional deficiency in vitamin Bj (thiamine). The active form of the vitamin, thiamine pyrophosphate, is a required cofactor for a-ketoglutarate dehydrogenase. 

Thiamine Vitamin Bp a water-soluble vitamin containing a thiazolium ring. The active form of the vitamin is thiamine pyrophosphate, which is an important coenzyme for many biochemical reactions. 

Thiamine (vitamin Bj) is an important water-soluble vitamin that, in its active form of thiamine pyrophosphate, is used as a cofactor in enzymatic reactions that involve the transfer of an aldehyde group. Thiamine can be synthesized by plants and some microorganisms, but not usually by animals. Hence, humans must obtain thiamine from the diet, though small amounts may be obtained from synthesis by intestinal bacteria. Because of its importance in metabolic reactions, it is present in large amounts in skeletal muscle, heart, liver, kidney, and brain. Thus, it has a widespread distribution in foods, but there can be a substantial loss of thiamine during cooking above 100°C (212°F). 

Thiamine is absorbed in the intestine by both active transport mechanisms and passive diffusion. The active form of the cofactor, thiamine pyrophosphate (thiamine diphosphate, TPP), is synthesized by an enzymatic transfer of a pyrophosphate group from ATP to thiamine (Figure 15-1). The resulting TPP has a reactive carbon on the thiazole ring that is easily ionized to form a carbanion, which can undergo nucleophilic addition reactions. 

Thiamine (vitamin Bj) is an important water-soluble vitamin that, in its active form of thiamine pyrophosphate, is used as a cofactor in enzymatic reactions that involve the transfer of an aldehyde group. 

The coenzyme thiamin diphosphate (ThDP, I in Scheme 16.1), the biologically active form of vitamin Bi, is used by different enzymes that perform a vide range of catalytic functions, such as the oxidative and nonoxidative decarboxylation of a-ketoacids, the formation of acetohydroxyacids and ketol transfer bet veen sugars. 

Partial protection from scurvy in guinea pigs provided by a-lipoic acid (R22) is probably due to the preservations of small residual amounts of ascorbic acid in the diet. Ascorbic acid has similar effects on riboflavin-(T4) and thiamine-deficient (T3) rats. The temporary improvements are the result of the reduction of thiamine disulfide to nutritionally active forms (B3). 

Thiamine, also known as vitamin B, is required in the diet of aU animals. Its biologically active form is the coenz)une thiamine p)rrophosphate. This coenzyme is required for many decarboxylation reactions, including the decarboxylation of... 

Thiamin pyrophosphate is the active form of thiamin and is used as an enzymatic cofactor. Two other physiologically active forms of thiamin have been identified ATP thiamin, which was recently identified as a stress metabolite in Escherichia coli, and thiamin triphosphate, " the exact physiological function of which is still unclear. 

A variety of models have been developed to study TD. TD in rodents can be produced in multiple ways. Simple deprivation of thiamine will deplete thiamine and thiamine-dependent processes. However, this expands the time until the symptoms occur, and increases the variability for time of the onset of the symptoms. Injection of inhibitors of thiamine utilization in conjunction with the thiamine deficient diet shortens the time until onset of symptoms and provides a remarkably reproducible model. Pyrithiamine, which is structurally similar to thiamine, blocks the thiamine pyrophospho kinase, which catalysis the phosphorylation of thiamine to thiamine pyrophosphate (TPP) so that the production of the metabolically active form of thiamine, TPP, is impaired. Pyrithiamine readily crosses the blood brain barrier so that TD is produced in the brain and in the periphery. On the other hand, oxythiamine does not cross the BBB and only produces TD in the periphery. The precise timing of the acute and chronic changes in TD varies with the model. All the models lead to diminished food intake, so, often paired fed controls are used. These have never shown that pathology is related to TD. 

---