D-sedoheptulose 7-phosphate

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. ... 

Formation of a possible precursor of 9, namely, o-glycero-D-manno-heptose 7-phosphate, from D-sedoheptulose 7-phosphate was demonstrated in Salmonella typhimurium.238... 

The hydroxyethylthiamine pyrophosphates are potent nucleophiles and may add to carbonyl compounds to form carbon-carbon bonds. A good illustration of carbon-carbon bond making and breaking occurs in the reactions of transketo-lase. The enzyme contains tightly bound thiamine pyrophosphate and shuttles a dihydroxyethyl group between D-xylulose 5-phosphate and D-ribose 5-phosphate to form D-sedoheptulose 7-phosphate and D-glyceraldehyde 3-phosphate (equations 2.55 and 2.56). 

D-Ribose 5-phosphate D-Xylulose 5-phosphate D-Sedoheptulose 7-phosphate D-Glyceraldehyde 3-phosphate... 

Scheme 5.53. Transketolase transfers the C1-C2 ketol unit of D-xylulose 5-phosphate onto D-ribose-5-phosphate or D-erythrose-4-phosphate generating D-sedoheptulose-7-phosphate or D-fructose-6-phosphate respectively. P = PO32-.

Like transketolase, transaldolase (TA, E.C. 2.2.1.2) is an enzyme in the oxidative pentose phosphate pathway. TA is a class one lyase that operates through a Schiff-base intermediate and catalyzes the transfer of the C(l)-C(3) aldol unit from D-sedoheptulose 7-phosphate to glyceraldehyde-3-phosphate (G3P) to produce D-Fru 6-P and D-erythrose 4-phosphate (Scheme 5.59). TA from human as well as microbial sources have been cloned.110 111 The crystal structure of the E. coliu and human112 transaldolases have been reported and its similarity to the aldolases is apparent, since it consists of an eight-stranded (o /(3)s or TIM barrel domain as is common to the aldolases. As well, the active site lysine residue that forms a Schiff base with the substrate was identified.14112 Thus, both structurally and mechanistically it is related to the type I class of aldolases. 

Scheme 5.59. Transaldolase catalyzed the transfer of the C1-C3 aldol unit of D-sedoheptulose-7-phosphate to D-glyceraldehyde-3-phosphate (G3P) generating D-fructose-6-phosphate and D-erythrose 4-phosphate. P = P032. ...

Despite the fact that many heptoses are by far less prominent in Nature than hexoses these monosaccharides are found both as metabolic intermediates, and as structural carbohydrates of bacterial cell walls.D-Sedoheptulose 7-phosphate is an important intermediate of the pentose cycle, and D-sedoheptulose 1,7-bisphosphate is present in plants as an intermediate of the dark phase of photosynthetic reactions. L-Glycero-D-manno-heptose was isolated from the oligosaccharides obtained by partial acid hydrolysis of the lipopolysaccharide from Escherichia coli K-12 strain W3100 [153] and Haemophilus influenzae [154]. Both L-glycero-D-wtanno-heptose and D-glycero-D-ma o-heptose were isolated from the lipopolysaccharide of Vibrio parahaemolyticus [155]. 

D-sedoheptulose 7-phosphate 4- v-glycero-trioae 3-phosphate transaldolase... 

TK is one of the enzymes involved in the oxidative pentose phosphate pathway, and requires the cofactors thiamine pyrophosphate (TPP)12191 and Mg2+[218). It reversibly transfers the C1-C2 ketol unit from D-xylulose 5-phosphate to D-ribose 5-phosphate, and generates D-sedoheptulose 7-phosphate and D-Gly 3-P. D-Erythrose 4-phosphate also functions as an acceptor of the ketol unit from D-xylulose 5-phosphate, to produce Fru 6-P and D-Gly 3-P (Fig. 14.2-1). TK from baker s yeast is commercially available, and the enzyme can also be isolated from spinach[220, 2211 TK from E. coli has been overexpressed and prepared on a large scale12221. In ketol transfer reactions,... 

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. 

Evidence from a number of sources indicated that pentose phosphates were metabolized in a series of reactions that resulted in the formation of hexose monophosphates and hexose diphosphates. Several enzyme steps are involved in these transformations. The reaction between D-ribulose 5-phosphate and D-ribose 5-phosphate to form D-sedoheptulose 7-phosphate and D-glyceraldehyde 3-phosphate is catalyzed by an enzyme known as transketolase (91). This enzyme is found in plant, animal, and bacterial cells. Thiamine pyrophosphate (TPP) and Mg ions are required as cofactors. The mechanism of the reaction was suggested (92) as shown in reaction (28). 

The specificity of purified transketolase is rather broad, and several compounds have been shown (93) to act as donors of active glycolaldehyde. Included in these compounds are D-ribulose 5-phosphate, D-sedoheptulose 7-phosphate, D-fructose 6-phosphate, L-erythrulose, and hydroxypyruvic acid. A number of aldehydes have been shown to act as active glycolalde-... 

The D-sedoheptulose 7-phosphate formed during the cleavage of the pentose phosphates is metabolized by the following reaction (29). The enzyme catalyzing this reaction is called transaldolase and is supposed to act by transferring a dihydroxyacetone group. Only D-sedoheptulose 7-phos-phate and D-fructose 6-phosphate have been shown to act as dihydroxyacetone donors, and D-glyceraldehyde 3-phosphate and D-erythrose 4-phos-phate as dihydroxyacetone acceptors 95). 

Figure IS.S Appearance of D-sedoheptulose-7-phosphate (d-S7P) against time monitored by LC/MS from four probes bearing different R groups, x, R = -CH3 R = -(CH2)2SCH3 (16b) A, R = -CH2CH(CH3)2 (16a) , R = -CHOH(R)CHj.

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