Dihydroxyacetone, from fructose

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).

Reaction of ribose 5-phosphate 116 with dihydroxyacetone phosphate, catalyzed by fructose 1,6-diphosphate aldolase from rabbit muscle (RAMA) affords the ketose diphosphate 117. Dihydroxyacetone phosphate was formed in situ from fructose 1,6-diphosphate by action of RAMA and triose phosphate isome-rase (TPI). The diphosphate 117 was dephosphorylated enzymatically using acid phosphatase, and the ketose 118 was reduced directly into the a-C-manno-side 119 by treatment with bistrimethylsilyltrifluoroacetamide, trimethylsilyl-triflate and triethylsilane (Scheme 28) [45]. 

Fig. 3.8. Formation of glyceraldehyde-3-phosphate and dihydroxyacetone-1-phosphate from fructose-1,6-diphosphate during fermentation...

Apart from fructose, the name always ends in -ulose. Some ketoses are not related structurally to dihydroxyacetone. They are named by considering the configurations of all the chiral carbon atoms as a unit, ignoring the carbonyl group. 

Chain-extended Compounds. - Unusual hexoses and higher carbon sugars have been produced by use of fructose 1,6-diphosphate aldolase which catalysed firstly, in combination with triosephosphate isomerase, the release of dihydroxyacetone phosphate (DHAP) from fructose 1,6-diphosphate and secondly the stereospecific condensation of DHAP with a variety of simple aldehydes. Two examples are given in Scheme 7. ... 

An indirect enzymatic pathway for the formation of uctose-6-phosphate from fructose-l-phosphate has recently been described by Leuthardt et al. Fructose-l-phosphate is cleaved to D-glyceraldehyde and dihydroxyacetone phosphate. The latter isomerizes to form glyceraldehyde-3-phosphate. The triose phosphates condense to fructose-1,6-diphosphate which is dephosphorylated at the 1 position. In the presence of ATP, the glyceraldehyde may be converted by means of a triosekinase to glyceraIdehyde-3-phosphate. 

Dihydroxyacetone phosphate is formed enzymically from fructose 1,6-diphosphate or by phosphorylation of dihydroxyacetone with ATP . Synthesis has been effected by phosphorylation of monoacetyldihydroxy-acetonedimethyl acetal . ... 

Fructose bisphosphate aldolase of animal muscle is a Class I aldolase, which forms a Schiff base or imme intermediate between the substrate (fructose-1,6-bisP or dihydroxyacetone-P) and a lysine amino group at the enzyme active site. The chemical evidence for this intermediate comes from studies with the aldolase and the reducing agent sodium borohydride, NaBH4. Incubation of fructose bisphosphate aldolase with dihydroxyacetone-P and NaBH4 inactivates the enzyme. Interestingly, no inactivation is observed if NaBH4 is added to the enzyme in the absence of substrate. 

The transaldolase functions primarily to make a useful glycolytic substrate from the sedoheptulose-7-phosphate produced by the first transketolase reaction. This reaction (Figure 23.35) is quite similar to the aldolase reaction of glycolysis, involving formation of a Schiff base intermediate between the sedohep-tulose-7-phosphate and an active-site lysine residue (Figure 23.36). Elimination of the erythrose-4-phosphate product leaves an enamine of dihydroxyacetone, which remains stable at the active site (without imine hydrolysis) until the other substrate comes into position. Attack of the enamine carbanion at the carbonyl carbon of glyceraldehyde-3-phosphate is followed by hydrolysis of the Schiff base (imine) to yield the product fructose-6-phosphate. 

Functionally related to FruA is the novel class I fructose 6-phosphate aldolase (FSA) from E. coli, which catalyzes the reversible cleavage of fructose 6-phosphate (30) to give dihydroxyacetone (31) and d-(18) [90]. It is the only known enzyme that does not require the expensive phosphorylated nucleophile DHAP for synthetic purpose. 

Figure 4.17 The trioses D-glyceraldehyde (aldose) and dihydroxyacetone (ketose), the pentose D-ribose, the hexoses D-galactose and D-glucose (aldoses) and the ketohexose D-fructose in their open chain forms. The configuration of the asymmetrical hydroxyl group on the carbon, the furthest away from the aldehyde or ketone group, determines the assignment of D- or L-configuration.

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