Adenosine thiamin diphosphate

Figure 5.4 Structural formulae of thiamin phosphate esters. At present, five natural thiamin phosphate derivatives have been described thiamin monophosphate (ThMP) thiamin diphopshate (ThDP) thiamin triphosphate (ThTP) adenosine thiamin diphosphate (AThDP) and adenosine thiamin triphosphate (AThTP). Catalytic intermediates, such as for instance a-hydroxyethyl thiamine diphosphate formed by the action of yeast pyruvate decarboxylase (EC 4.1.1.1), are not considered here.

ThTP through its ability to phosphorylate proteins (Nghiem et al. 2000). Thiamin is the only known natural organic molecule that is not a nucleotide but forms mono-, di- and triphospho-derivatives. Recently, even thiamin adenylated derivatives have been described adenosine thiamin diphosphate (AThDP) and adenosine thiamin triphosphate (AThTP) (Bettendorff et al. 2007 Frederich et al. 2009). 

Berthold CL, P Moussatche, NGJ Richards, Y Lindqvist (2005) Structural basis for activation of the thiamin diphosphate-dependent enzyme oxalyl-CoA decarboxylase by adenosine diphosphate. J Biol Chem 280 41645-41654. 

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). 

Makarchikov, A.F., Brans, A., and Bettendorff, L., 2007. Thiamine diphosphate adenylyl transferase from E. coli functional characterization of the enzyme synthesizing adenosine thiamine triphosphate. BMC Biochemistry. 8 17. 

Thiamine can be considered to be the product of the quatemization of 4-methyl-5-(2-hydroxymethyl)thiazole (5) by an active derivative of 4-amino-5-(hydroxymethyl)-2-methyl pyrimidine (4) (Scheme 2). In living cells, pyramine can be activated by conversion into the diphosphate 7, via monophosphate 6, and the substrate of the enzyme responsible for the quatemization is not the thiamine thiazole, but its phosphate 8. The product of the condensation, thiamine phosphate (9), is finally converted into diphosphate 2—the biochemically active derivative—by hydrolysis to free thiamine, followed by diphosphorylation, or more directly, in some cases. Enzymes are known for all of the steps depicted in Scheme 2, and adenosine triphosphate (ATP) is, as usual, the phosphate donor. 

The three tissue enzymes known to participate in formation of the phosphate esters are (1) thiaminokinase (a pyro-phosphokinase), which catalyzes formation of TPP and adenosine monophosphate (AMP) from thiamine and adenosine triphosphate (ATP) (2) TPP-ATP phosphoryl-transferase (cytosoHc 5"-adenylic kinase)which forms the triphosphate and adenosine diphosphate from TPP and ATP and (3) thiamine triphosphatase, which hydrolyzes TPP to the monophosphate. Although thiaminokinase is widespread, the phosphoryl transferase and membrane-associated triphosphatase are mainly in nervous tissue. 

TOBACCO [NicoTiANA TABACUM L.) Fractions M-Ia and M-Ib from acid phosphatase of tobacco cells did not hydrolyse phosphate monoesters except para-nitrophenyl phosphate, but hydrolysed phosphoric anhydrides (inorganic pyrophosphate, thiamine pyrophosphate, nucleoside di- and triphosphates). In addition, both fractions hydrolysed bis-para-nitrophenyl phosphate. Fraction M-II, a non-specific acid phosphatase, had broad substrate specificity it hydrolysed pyrophosphate, thiamine pyrophosphate, uridine diphosphate, adenosine triphosphate, uridine triphosphate, and cytidine triphosphate, at rates similar to para-nitrophenyl phosphate (Ninomiya et al., 1977). 

The pyrophosphate bond of DPN is ruptured by an enzyme found in kidney particles and in potatoes. The potato enzyme has been purified over 750-fold and found also to cleave the pyrophosphate linkages of reduced DPN, TPN, flavinadenine dinucleotide, adenosine diphosphate, adenosine triphosphate, and thiamine pyrophosphate. 

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