Thiamin monophosphate synthesis

In brain, as in most mammalian cells, thiamine occurs predominantly in the form of TDP, the remainder being made up of thiamine monophosphate (10%), thiamine triphosphate (5-10%) and trace amounts of free thiamine. Thiamine is transported into brain and phosphory-lated by the action of thiamine pyrophosphokinase, and inhibition of this enzyme by thiamine antagonists such as pyrithiamine results in decrease synthesis of TDP. Treatment of experimental animals with pyrithiamine results in a generalized reduction of TDP concentrations and an early selective loss in activity of a-KGDH in regions... 

Thiamin is synthesized in bacteria, fungi, and plants from 1-deoxyxylulose 5-phosphate (Eq. 25-21), which is also an intermediate in the nonmevalonate pathway of polyprenyl synthesis. However, thiamin diphosphate is a coenzyme for synthesis of this intermediate (p. 736), suggesting that an alternative pathway must also exist. Each of the two rings of thiamin is formed separately as the esters 4-amino-5-hydroxy-methylpyrimidine diphosphate and 4-methyl-5-((i-hydroxyethyl) thiazole monophosphate. These precursors are joined with displacement of pyrophosphate to form thiamin monophosphate.92b In eukaryotes this is hydrolyzed to thiamin, then converted to thiamin diphosphate by transfer of a diphospho group from ATP.92b c In bacteria thiamin monophosphate is converted to the diphosphate by ATP and thiamin monophosphate kinase.92b... 

The final step in the synthesis of thiamin involves condensation between the hydroxymethylpyrimidine diphosphate andhydroxyethylthiazole monophosphate to yield thiamin monophosphate, which can then be dephosphorylated to free thiamin or phosphorylated further to the diphosphate and triphosphate (Hohmann and Meacock, 1998 Begley et al., 1999). 

S ATP + 4-methyl-5-(2-hydroxyethyl)thiazole <1, 2> (<1> enzyme involved in biosynthesis of thiamine [1] <1> the bifunctioinal enzyme hydroxyethylthiazole kinase/thiamine-phosphate pyrophosphorylase catalyzes two sequential steps in the synthesis of thiamin monophosphate from hydroxyethylthiazole [2] <2> the enzyme is a salvage enzyme in the thiamin biosynthetic pathway and enables the cell to use recycled 4-methyl-5-j8-hydroxyethylthiazole as an alternative to its synthesis from 1-deoxy-o-xylulose-5-phosphate, cysteine, and tyrosine [3]) (Reversibility <1, 2> [1,2,3]) [1,2, 3]... 

Thus a thiamine derivative plays a metabolic role as cocarboxylase, which has been found to be inactivated by a specific phosphatase of yeast (122,123). The inactivation was inhibited by thiamine itself and to a lesser degree by thiamine monophosphate and the pyrimidine constituent of the thiamine molecule. Synthesis and breakdown of thiamine by Phycomyces species have also been studied (9,45,98). Pyridoxine derivatives are now known to catalyze two t3T)cs of bacterial reactions, involving transamination and decarboxylation of amino acids (4,32,35,59). Interconversion between members of the group of substances of natural occurrence which are related to pyridoxine has been observed in microorganisms and appears likely to afford a series of changes comparable to those observed in nicotinic acid dreivatives. Production of folic acid from chemically defined precursors by bacterial suspensions has also been observed (110,111). 

The synthesis of TPP from thiamine has been carried out by several pyrophosphorylation procedures. The usual procedure involves the reaction of thiamine and polyphosphoric acid obtained by heating orthophosphoric acid. Velluz pointed out that the primary product in this procedure was thiamine triphosphoric acid. Viscontini, Bonetti, and Karrer worked out the details for obtaining thiamine tri-, pyro- and monophosphates in good yield. 

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