Sugar phosphates dihydroxyacetone phosphate

The glycolytic enzyme triosephosphate isomerase (TIM) catalyzes the interconversion of the sugar phosphates dihydroxyacetone phosphate (DHAP) and D-glyceraldehyde 3-phosphate (GAP). Although the reaction is extremely fast, the enzyme is an attractive candidate for mapping... 

The lower-carbon, phosphorylated sugars, so important in biochemical processes, also came in for the further attention of Fischer and Ballou. New methods of synthesis were worked out for 2-0-phospho-o-glyceric acid, D-glyceraldehyde 3-phosphate, dihydroxyacetone phosphate, and (with Dr. MacDonald) the enantiomorphous erythrose 4-phosphates. The suspected biochemical importance of the n-erythrose 4-phosphate was then quickly established when Srinivasan, Katagiri, and Sprinson of Columbia University demonstrated its condensation with 0-phospho-enolpyruvic acid to 5-dehydroshikimic acid by Escherichia coli. 

D-Sorbose Sugar Phosphates by Enzymatic Addition of Dihydroxyacetone Phosphate to Aldehydes Typical Procedure8 ... 

Figure 10.18 Enzymatic in situ generation of dihydroxyacetone phosphate from fructose 1,6-bisphosphate (b), with extension to an in vitro artificial metabolism for its preparation from inexpensive sugars alongthe glycolysis cascade (a), and utilization for subsequent stereoselective carbon-carbon bond formation using an aldolase with distinct stereoselectivity (c).

Fessner, W.D., and Sinerius, G., Synthesis of dihydroxyacetone phosphate (and isosteric analogues) by enzymatic oxidation sugars from glycerol. Angew. Chem. bit. Ed. Engl, 1994, 33, 209. 

In nature, most aldolases are rooted in the sugar metabolic cycle and accept highly functionalized substrates for the aldol reaction. Nevertheless, the scope of enzymatic aldol reactions is limited, since aldolases strictly distinguish between the acceptor and the donor, yielding almost exclusively one product, and is furthermore restricted to only a few different possible natural donors. According to the donor molecules, aldolases are grouped in dihydroxyacetone phosphate-, phosphoenolpyruvate- or pyruvate-, acetaldehyde-, and glycine-dependent aldolases [41]. 

Fructose 1,6-biphosphate aldolase from rabbit muscle in nature reversibly catalyzes the addition of dihydroxyacetone phosphate (DHAP) to D-glyceraldehyde 3-phosphate. The tolerance of this DHAP-dependent enzyme towards various aldehyde acceptors made it a versatile tool in the synthesis of monosaccharides and sugar analogs [188], but also of alkaloids [189] and other natural products. For example, the enzyme-mediated aldol reaction of DHAP and an aldehyde is a key step in the total synthesis of the microbial elicitor (—)-syringolide 2 (Fig. 35a) [190]. 

The results reveal that baker s yeast is a potent source for precursors of 2-acetyl-l-pyrroline. It appears likely that the flavor compound is formed in the yeast cells from proline and dihydroxyacetone phosphate via 1-pyrroline and pyruvaldehyde. This is corroborated by the results of c-labeling experiments which showed that the acetyl group in the Acp stems from a sugar degradation product and that the pyrroline ring was derived from proline. 

A reaction involved in the metabolism of sugars is the splitting of fructose- 1,6-diphosphate to give glyceraldehyde-3-phosphate and dihydroxyacetone phosphate. In the living system, this retro-aldol is catalyzed by an enzyme called aldolase however, it can also be catalyzed by a mild base. Propose a mechanism for the base-catalyzed reaction. 

In this sense, enzymatic catalysis is especially attractive for syntheses demanding highly regio- and stereoselectivity. Particularly dihydroxyacetone phosphate (DHAP) dependent aldolases are among the most suitable biocatalyst for imino-sugar synthesis due to their high stereoselectivity and chiral induction capacity [10, 12, 13]. The aldol addition of DHAP (1) to a synthetic equivalent of an... 

Enzymes turned out to be very helpful in the de novo synthesis of certain monosaccharides. Generally, two chiral carbonyl compounds are combined in an aldol-type reaction. In carbohydrate metabolism, aldolases catalyze the condensation of dihydroxyacetone phosphate (DHAP) and aldehydes to higher sugar components. To date, about thirty aldolases have been classified, but only... 

The enzymatic aldol reaction represents a useful method for the synthesis of various sugars and sugar-like structures. More than 20 different aldolases have been isolated (see Table 13.1 for examples) and several of these have been cloned and overexpressed. They catalyze the stereospecific aldol condensation of an aldehyde with a ketone donor. Two types of aldolases are known. Type I aldolases, found primarily in animals and higher plants, do not require any cofactor. The x-ray structure of rabbit muscle aldolase (RAMA) indicates that Lys-229 is responsible for Schiff-base formation with dihydroxyacetone phosphate (DHAP) (Scheme 13.7a). Type II aldolases, found primarily in micro-organisms, use Zn as a cofactor, which acts as a Lewis acid enhancing the electrophilicity of the ketone (Scheme 13.7b). In both cases, the aldolases accept a variety of natural (Table 13.1) and non-natural acceptor substrates (Scheme 13.8). 

Fructose-1,6-diphosphate aldolase of rabbit muscle has been studied very extensively-and it is now commercially available. That of spinach leaves, obviously very accessible, was recently examined (Valentin and Bolte 1993). In the fundamental reaction of glycolysis (reaction 6.8), the donor is dihydroxyacetone phosphate. It can scarcely be varied, but there is more flexibility with the acceptor (David et al. 1991 Bednarski et al. 1989), and sometimes we can wander considerably from the subject of sugar chemistry. In any case, the vicinaZ-diol created at positions 3 and 4 (uloses numbering) has the D-threo configuration. Hence the condensation of the keto aldehyde 6.28 gives ketose 6.29 which, after isolation, is dephosphorylated enzymically in the presence of acid phosphatase. 

In aldol condensation, aldehydes and ketones react to form a larger molecule (Section 14.4). This reaction is a reverse aldol condensation. The large ketone sugar fructose-l,6-bisphosphate is broken down into dihydroxyacetone phosphate (a ketone) and gIyceraldehyde-3-phosphate (an aldehyde). 

The enzyme name hints that two isomers of a phosphorylated three-carbon sugar are going to be interconverted (Section 20.1). The ketone dihydroxyacetone phosphate and its isomeric aldehyde, phosphoglyceraldehyde-3-phosphate are interconverted through an enediol intermediate. 

Figure 13. Flow of carbon from dihydroxyacetone phosphate to phosphoglyceraldehyde (and, with oxidation, to 3-phosphoglyceric acid and biomass) and to Cg sugars. As shown, fructose-1,6-bisphosphate can be formed by combining dihydroxyacetone phosphate and phosphoglyceraldehyde. The further sugar shown has the structure of glucose (stereochemistry not shown). Carbon positions in such aldohexoses are numbered 1-6, starting with the aldehydic carbon. The processes...

Type A enzymes use dihydroxyacetone phosphate (DAHP) as the nucleophilic substrate and, by reacting with an aldehyde, form a ketose 1-phosphate sugar. 

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