Thiamin coenzymes derived from

The pyruvate decarboxylase reaction provides our first encounter with thiamine pyrophosphate (TPP) (Fig. 14-13), a coenzyme derived from vitamin B Lack of vitamin Bi in the human diet leads to the condition known as beriberi, characterized by an accumulation of body fluids (swelling), pain, paralysis, and ultimately death. 

Although the nicotinamide nucleotide coenzymes function in a large number of oxidation and reduction reactions, thus carmot be exploited as a means of assessing the state of the body s niacin reserves, because the coenzymes are not firmly attached to their apoenzymes, as are coenzymes derived from thiamin (Section 6.5.3), riboflavin (Section 7.5.3), and vitamin Be (Section 9.5.3), but act as cosubstrates of the reactions, binding to and leaving the enzyme as... 

Ethanol is formed from pyruvate in yeast and several other microorganisms. The first step is the decarboxylation of pyruvate. This reaction is catalyzed by pyruvate decarboxylase, which requires the coenzyme thiamine pyrophosphate. This coenzyme, derived from the vitamin thiamine (Bj), also participates in reactions catalyzed by other enzymes (Section 17.1.1). The second step is the reduction of acetaldehyde to ethanol by NADH, in a reaction catalyzed by... 

This single reaction requires four coenzymes made from four different vitamins, in addition to the coenzyme lipoamide. These are thiamine pyrophosphate, derived from thiamine (Vitamin B ) FAD, derived from riboflavin (Vitamin B2) ... 

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,). 

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... 

Branched-chain ketoaciduria (commonly known as Maple Syrup Urine Disease MSUD) is another ailment that may be caused by thiamine deficiency. In MSUD, the oxidative decarboxylation of alpha-keto acids derived from, i.e. valine, isoleucine, and leucine, is blocked due to an inadequate supply of the coenzyme thiamine pyrophosphate (TPP). Clinical symptoms of MSUD include mental and physical retardation. Describe briefly the structure of Riboflavin (Vitamin B-2) and its biochemical role. 

Other cofactors involved in deriving energy from food include coenzyme A (derived from the vitamin pantothenate), thiamine pyrophosphate, and Upoic acid. 

Although ubiquitin has not been found in prokaryotes, ubiquitin s molecular ancestors were recently identified in prokaryotes. Remarkably, these proteins take part not in protein modification but in biosynthesis of the coenzyme thiamine (p. 423). A key enzyme in thiamine biosynthesis is ThiF, which activates the protein ThiS as an acyl adenylate and then adds a sulfide ion derived from cysteine (Figure 23.9). ThiF is homologous to human Ft, which includes two tandem regions of 160 amino acids that arc 28% identical in amino acid sequence with a region of ThiF from E. coli. 

Nakanishi, I., Itoh, S., Suenobu, T, Fukuzumi, S. (1997a), Electron transfer properties of active aldehydes derived from thiamin coenzyme analogues, Chem. Commun. 19, 1927-1928. 

TPP is used as a coenzyme for all decarboxylations of oi-keto acids. It is derived from thiamine (Vitamin Bl) by transfer of a pyrophosphate group from ATP to thiamine, yielding TPP and AMP. 

Thiamine pyrophosphate (TPP) is derived from thiamine (vitamin Bl) via an ATP-dependent pyrophosphorylation. TPP is the coenzyme for all decarboxylations of ot-keto acids. Steps in the process are depicted in Figure 14.6, summarized below. 

Two coenzymes which are involved in most of the redox reactions of metabolism are nicotine adenine dinucleotide, NAD", and FAD, flavine adenine dinucleotide. Most metabolic oxidations are, in fact, dehydrogenations, and not reactions with oxygen. Nicotinamide is derived from nicotinic acid, and the isoalloxazine ring of FAD is derived from riboflavin. Thiamin is the principal cofactor in enzymatic decarboxylations. Many of the vitamins serve as coenzymes in a wide variety of cellular reactions. 

A newly isolated soil bacterium grows without oxygen but requires ferric ion in the growth medium. Succinate suffices as a carbon source, but neither hexoses nor pyruvate can be utilized. The bacteria require riboflavin as a growth supplement. Neither niacin nor thiamin is required, and neither substance nor compounds derived from them can be found in the cells. The electron carriers found in the bacteria are cytochrome b, cytochrome c, FAD, and coenzyme Q. 

The oxidative decarboxylation of pyruvate is considerably more complex than is suggested by the preceding equation. In addition to utilizing NAD and coenzyme A, this transformation also requires FAD, thiamine pyrophosphate (which is derived from thiamine, vitamin Bl), and lipoic acid ... 

In this section a method developed by Schultz, Atkin and Frey may also be mentioned, based on the stimulation by thiamine of the fermentation of glucose by baker s yeast (S. cerevisiae) in the presence of ammonium sulfate. Carried out in a Warburg apparatus, it can measure 0.01-0.02 fig of thi-amine32. jiiis method has been widely used. The effect of thiamine on fermentation has been shown to depend quantitatively upon the formation of carboxylase the coenzyme being derived from thiamine, and ammonium sulfate in the medium providing material for the synthesis of enzyme protein . Under the circumstances of the test carboxylase is evidently a Umiting enzyme for fermentation. 

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. 

The metabolic functions of pantothenic acid in human biochemistry are mediated through the synthesis of CoA. Pantothenic acid is a structural component of CoA. which is necessary for many important metabolic processes. Pantothenic acid is incorporated into CoA by a. series of five enzyme-catalyzed reactions. CoA is involved in the activation of fatty acids before oxidation, which requires ATP to form the respective fatty ocyl-CoA derivatives. Pantothenic acid aI.so participates in fatty acid oxidation in the final step, forming acetyl-CoA. Acetyl-CoA is also formed from pyruvate decarboxylation, in which CoA participates with thiamine pyrophosphate and lipoic acid, two other important coenzymes. Thiamine pyrophosphate is the actual decarboxylating coenzyme that functions with lipoic acid to form acetyidihydrolipoic acid from pyruvate decarboxylation. CoA then accepts the acetyl group from acetyidihydrolipoic acid to form acetyl-CoA. Acetyl-CoA is an acetyl donor in many processes and is the precursor in important biosyntheses (e.g.. those of fatty acids, steroids, porphyrins, and acetylcholine). 

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

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