Sedoheptulose-7-phosphate, synthesis

Transketolase (TKase) [EC 2.2.1.1] essentially catalyzes the transfer of C-2 unit from D-xylulose-5-phosphate to ribose-5-phosphate to give D-sedoheptulose-7-phosphate, via a thiazolium intermediate as shown in Fig. 16. An important discovery was that hydroxypyruvate works as the donor substrate and the reaction proceeds irreversibly via a loss of carbon dioxide (Fig. 17). In this chapter, we put emphasis on the synthesis with hydroxypyruvate, as it is the typical TPP-mediated decarboxylation reaction of a-keto acid. ... 

The sugar metabolism is a source of many enzymes, the transketolase (TK) being one of them. TK transfers an a-hydroxy carbonyl fragment from D-xylu-lose-5-phosphate onto D-ribose-5-phosphate, forming D-sedoheptulose-7-phos-phate and D-glyceraldehyde-3-phosphate (Scheme 5.14). Since this reaction is an equilibrium reaction and starting materials and products are of similar stability, it is not very versatile for organic synthesis. Fortunately TK also accepts pyruvate instead of xylulose. Under these modified circumstances carbon dioxide... 

TA is also an enzyme of the oxidative pentose phosphate pathway[218). It catalyzes the transfer of the C1-C3 aldol unit from D-sedoheptulose 7-phosphate to D-Gly 3-P, and produces D-Fru 6-P and D-erythrose 4-phosphate (Fig. 14.2-3). TA forms a Schiffbase intermediate and does not require any co-factors. This enzyme is commercially available, and was used in a multi-enzyme synthesis of D-Fru from starch (Fig. 14.2-4) 1233] Here, it accomplished transfer of an aldol moiety from Fru 6-P to d-glyceraldehyde, and formed D-Gly 3-P and D-Fru. 

V. Klybas, M. Schramm, and E. Racker, Oxidative pentose phosphate cycle. IV. Synthesis of sedoheptulose 1,7-diphosphate, sedoheptulose 7-phosphate, glyceraldehyde 3-phosphate, and glycolaldehyde phosphate, Arch. Biochem. Biophys., 80 (1959) 229-235. 

Rifamycins.—Contained within the rifamycin skeleton, for example that of rifamycin S (169), is a C7-N unit (heavy bonding) which has been deduced to arise from an intermediate of the shikimic acid pathway. Fresh evidence arising from a study using mutants of Nocardia meditenanei confirms this view, and it is apparent that divergence from the shikimate pathway to rifamycin synthesis occurs between sedoheptulose-7-phosphate and shikimic acid itself. 

From my laboratory and the laboratories of Ef Racker, Frank Dickens and Melvin Calvin, the years that followed witnessed a series of parallel and often highly synergistic discoveries on the nature of the pentose phosphate pathway and the path of carbon in photosynthesis. Andrew Benson and others in Calvin s laboratory, had shown that phosphate esters of ribulose and sedoheptulose were early products of CO2 fixation in photosynthesis,and the immediate precursor of phosphoglyceric acid, and therefore the primary CO2 acceptor, appeared to be ribulose diphosphate. The major problems became (1) to find the enzyme or enzymes that catalyzed the formation of phosphoglyceric acid from ribulose diphosphate and (2) to define the reactions leading to the synthesis of ribulose diphosphate from triose and hexose phosphates. 

A rapid, high yield synthesis of C-enriched intermediates of the pentose-phosphate pathway has been developed based on a combination of chemical and enzymic reactions. [l- C]Ribose and [l- C]arbinose 5-phospha,tes, available by the classical Kiliani method, were converted to a variety of specifically labelled 5-, 6-, 7-, and 8-carbon sugar phosphates (e.g.. D-erythro-pentulosc 5-phosphate, sedoheptulose mono- and di-phosphates) with the help of aldolase, transaldolase, and transketolase. ... 

Sedoheptulose 7-phosphate was found to be converted to dehydroshikimic acid about as well as various phosphorylated hexoses. When the heptose phosphate was incubated together with fructose 1,6-diphosphate the degree of conversion was doubled. This led to the suggestion that a reaction product, sedoheptulose 1,7-diphosphate might be the more direct substrate. Test of sedoheptulose 1,7-diphosphate yielded a very high conversion to dehydroshiki c acid (20%). When DPN was added to this, the degree of conversion was almost quantitative (80 %). Since the synthesis of dehydroshikimic acid from sedoheptulose diphosphate involves the removal of two hydrogens as well as two molecules of water, participation of a pyridine nucleotide is understandable. 

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