Thiamin vitamin diphosphate

Thiamine (vitamin Bi), in the form of thiamine diphosphate (TPP), is a coenzyme of some considerable importance in carbohydrate metabolism. Dietary deficiency leads to the condition beriberi, characterized by neurological disorders, loss of appetite, fatigue, and muscular weakness. We shall study a number of... 

Figure 22-2 The glyceraldehyde 3-phosphate pyruvate alternative pathway of isoprenoid biosynthesis. The intermediate 1-deoxyxylulose 5-phosphate may enter terpenes, vitamin B6, and thiamin. Isopentenyl diphosphate is shown as the final product, but the intermediate steps are uncertain. See Lange et al 2 ...

Vitamin Bj Vitamin Bj was discovered in 1926 by Jansen and Do-NATH, who synthesized it in its crystalline form from rice bran. It was initially called aneurine due to its antipolyneuropathic effect. Because it contains sulphur, Windaus correctly renamed it thiamine in 1932, a term by which it is still known today. The stixicture of this vitamin was described by Williams and Grewe in 1936. It is made up of pyrimidine and thiazole. Thiamine occurs in nature as free thiamine and in the form of thiamine monophosphate, diphosphate and triphosphate. A maximum amount of 8 — 15 mg is absorbed daily in the proximal portion of the small intestine. In the case of oversupply, thiamine is neither stored nor intestinally absorbed. A regular intake, with a daily requirement of about 1 mg, is necessary. The major coenzyme is thiamine pyrophosphate (TPP). Thiamine deficiency may be caused by malnutrition, impaired absorption, alcoholism, antithiamines or a lack of magnesium. Magnesium is an important cofactor for the coenzyme thiamine pyrophosphate. 

Studies on thiamine (vitamin Bi) catalyzed formation of acyloins from aliphatic aldehydes and on thiamine or thiamine diphosphate catalyzed decarboxylation of pyruvate have established the mechanism for the catalytic activity of 1,3-thiazolium salts in carbonyl condensation reactions. In the presence of bases, quaternary thiazolium salts are transformed into the ylide structure (2), the ylide being able to exert a cat ytic effect resembling that of the cyanide ion in the benzoin condensation (Scheme 2). Like cyanide, the zwitterion (2), formed by the reaction of thiazolium salts with base, is nucleophilic and reacts at the carbonyl group of aldehy s. The resultant intermediate can undergo base-catalyzed proton... 

Thiamin (Vitamin Bl), biosynthesized by most prokaryotes and eukaryotes in its active form thiamin diphosphate (ThDP), is an essential cofactor for several enzymes involved in carbohydrate and amino acid metabolism. Most bacteria, as well as fungi and plants, are able to produce thiamin de novo, while mammals depend solely on the dietary uptake [335-337],... 

Thiamine derivatives Thiamine diphosphate (D 10.4.5) Coenzyme of keto acid decarboxylase (C 4) and transketolases, in humans formed from thiamine (vitamin Bj)... 

Thiamin (vitamin Bi) is a complex nitrogenous base containing a pyrimidine ring joined to a thiazole ring. Because of the presence of a hydroxyl group at the end of the side chain, thiamin can form esters. The main form of thiamin in animal tissues is the diphosphate ester, commonly known as thiamin pyrophosphate (TPP).The vitamin is very soluble in water and is fairly stable in mildly acidic solution but readily decomposes in neutral solutions. 

Figure 1.1 Thiamin (Vitamin Bi) and thiamin diphosphate. The diphosphate ester of thiamin is the coenzyme form of thiamin.

The biologically active form of thiamine (vitamin Bi) is thiamine diphosphate (ThDP), in which a diphosphate group is attached to the thiazole ring of thiamine. ThDP was formally known as cocarboxylase , which is required for the decarboxylation reaction of pyruvate decarboxylase (PDC) from yeast. In 1937, Lohmann and Schuster established that the coenzyme cocarboxylase is ThDP (Lohmann and Schuster 1937). Enzymes requiring ThDP as a cofactor... 

Thiamin (thiamine, vitamin Bi), also formerly called aneurin (antineuritic factor), is a water-soluble vitamin of the B group. Like other B vitamins, thiamin is the precursor of an important coenzyme, thiamin diphosphate (ThDP), required for the oxidative decarboxylation of 2-oxo acids. However, in contrast to other B vitamins, non-cofactor roles have been proposed for thiamin derivatives. These could be mediated by two triphosphate derivatives, thiamin triphosphate (ThTP) and the recently discovered adenosine thiamin triphosphate (AThTP) (Bettendorff et al. 2007). 

Figure 11.12 Thiamin vitamin B ) and the coenzyme thiamin diphosphate.

Many, although not all, coenzymes are derived from vitamins—substances that an organism requires for growth but is unable to synthesize and must receive in its diet. Coenzyme A from pantothenate (vitamin B3), NAD" from niacin, FAD from riboflavin (vitamin B2), tetrahydrofolate from folic acid, pyridoxal phosphate from pyridoxine (vitamin Be), and thiamin diphosphate from thiamin (vitamin Bi) are examples (Table 19.3). We ll discuss the chemistry and mechanisms of coenzyme reactions at appropriate points later in the text. 

Vitamin Bi [1] exists in nature both in free (thiamin) and esterified form (thiamin monophosphate, diphosphate, and triphosphate), while thiamin hydrochloride is used as a supplement [4]. To evaluate the total content of vitamin Bi in a food, extraction usually consists of an acid hydrolysis (0.1 M HCl in a water bath at 100°C or in an autoclave at 121°C) followed by an enzymatic digestion (diastases possessing a phosphatase activity) [1,2,5,6]. The acid treatment frees protein-boimd forms and converts starch into soluble sugars. The enzymatic treatment may require several hours (on average 3 hr) of incubation for complete dephosphorylation of the thiamin esters. 

Thiamine (vitamin Bj, also formerly known as aneurine) contains a pyrimidine ring (4-amino-2-methylpyrimidine) attached by the methylene group at C-5 to the nitrogen of 5-(2-hydroxyethyl)-4-methylthiazole. Thiamine (5-51) occurs primarily as a free compound and in the form of phosphate esters (5-52), the monophosphate, diphosphate (pyrophosphate called cocarboxylase) and triphosphate. 

Stepl of Figure 29.11 Addition of Thiamin Diphosphate The conversion of pyruvate to acetyl CoA begins by reaction of pyruvate with thiamin diphosphate, a derivative of vitamin B(. Formerly called thiamin pyrophosphate, thiamin diphosphate is usually abbreviated as TPP. The spelling thiamine is also correct and frequently used. 

Pyruvate is oxidized to acetyl-GoA by a multienzyme complex, pyruvate dehydrogenase, that is dependent on the vitamin cofactor thiamin diphosphate. 

In most organisms undergoing aerobic metabolism, pyruvate is oxidized to acetyl-CoA in a complex process involving its decarboxylation (Eq. 10-6). This oxidative decarboxylation, like the decarboxylation of pyruvate to acetaldehyde, requires thiamin diphosphate. In addition, an array of other catalysts participate in the process (see Fig. 15-15). Among these are the electron carrier flavin adenine diphosphate (FAD), which is derived from the vitamin riboflavin. Like NAD+, this... 

Compounds, often derivatives of vitamins that, while in the active site of the enzyme, alter the structure of a substrate in a way that permits it to react more readily. Coenzyme A, pyridoxal phosphate, thiamin diphosphate, and vitamin B12 coenzymes fall into this group. 

Why do we need vitamins Early clues came in 1935 when nicotinamide was found in NAD+ by H. von Euler and associates and in NADP+ by Warburg and Christian. Two years later, K. Lohman and P. Schuster isolated pure cocarboxylase, a dialyz-able material required for decarboxylation of pyruvate by an enzyme from yeast. It was shown to be thiamin diphosphate (Fig. 15-3). Most of the water-soluble vitamins are converted into coenzymes or are covalently bound into active sites of enzymes. Some lipid-soluble vitamins have similar functions but others, such as vitamin D and some metabolites of vitamin A, act more like hormones, binding to receptors that control gene expression or other aspects of metabolism. 

Except for some vitamin B12-dependent reactions, the cleavage or formation of carbon-carbon bonds usually depends upon the participation of carbonyl groups. For this reason, carbonyl groups have a central mechanistic role in biosynthesis. The activation of hydrogen atoms (3 to carbonyl groups permits (3 condensations to occur during biosynthesis. Aldol or Claisen condensations require the participation of two carbonyl compounds. Carbonyl compounds are also essential to thiamin diphosphate-dependent condensations and the aldehyde pyridoxal phosphate is needed for most C-C bond cleavage or formation within amino acids. 

The vitamins K and other naphthoquinones arise from O-succinylbenzoate84 86 whose synthesis from chorismate and 2-oxoglutarate depends upon a thiamine diphosphate-bound intermediate, as indicated in Fig. 25-4. Elimination of pyruvate yields O-succinylbenzoate. The remaining reactions of decarboxylation, methylation, and prenylation (Fig. 25-4) resemble those of ubiquinone synthesis. 

This vitamin acts as a coenzyme in the metabolism of carbohydrates and is present in all living tissues. It acts in the form of thiamin diphosphate in the decarboxylation of a-keto acids and is referred to as cocarboxylase. Thiamin is available in the form of its chloride or nitrate, and its structural formula is shown in Figure 9-12. The molecule contains two basic nitrogen atoms one is in the primary amino group, the other in the quater-... 

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