Fructose 1-phosphate, aldolase action

Subsequent action by fructose-l-phosphate aldolase cleaves fructose-l-P in a manner like the fructose bisphosphate aldolase reaction to produce dihy-droxyacetone phosphate and D-glyceraldehyde ... 

DHAP is a glycolysis intermediate, whereas glyceraldehyde must be reduced by a mitochondrial enzyme, glyceraldehyde dehydrogenase, to glycerol, which is then subject to action by glycerol kinase in the liver. The aldolase seems to be the principal pathway of metabolizing fructose and depends on the initial phosphorylation step catalyzed by fructokinase, which produces fructose-l-phosphate. Fructokinase is defective in an inherited disorder, essential fructosuria. Fructose-l-phosphate aldolase is deficient in the hereditary disorder fructose intolerance. 

An economically viable alternative to the synthesis of deoxyribonuclosides has been developed as a two stage process involving 2-deoxy-D-ribose 5-phosphate aldolase (DERA) (Fig. 6.5.14) (Tischer et al. 2001). The first step was the aldol addition of G3P to acetaldehyde catalyzed by DERA. G3P was generated in situ by a reverse action of EruA on L-fructose-1,6-diphosphate and triose phosphate isomerase which transformed the DHAP released into G3P. In a second stage, the action of pentose-phosphate mutase (PPM) and purine nucleoside phosphorylase (PNP), in the presence of adenine furnished the desired product. The released phosphate was consumed by sucrose phosphorylase (SP) that converts sucrose to fructose-1-phosphate, shifting the unfavorable equilibrium position of the later reaction. 

Holzer and Holzer (170) demonstrated aldolase action in extracts of Chlorella acetone powders. Studies on nonphotos5Tithetic plant tissues showed aldolase to be present in pea seeds (338) and potato tubers (34). Cardini (72) found that the aldolase of jackbeans in addition to acting on fructose-1,G diphosphate will split fructose-1-phosphate into dihydroxyacetone phosphate and glyceraldehyde. 

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]. 

Fructose bisphosphate is cleaved by action of an aldolase (reaction 4) to give glyceraldehyde 3-phosphate and dihydroxyacetone phosphate. These two triose phosphates are then equilibrated by triose phosphate isomerase (reaction 5 see also Chapter 13). As a result, both halves of the hexose can be metabolized further via glyceraldehyde 3-P to pyruvate. The oxidation of glyceraldehyde 3-P to the corresponding carboxylic acid, 3-phosphoglyceric acid (Fig. 17-7, reactions 6 and 7), is coupled to synthesis of a molecule of ATP from ADP and P . This means that two molecules of ATP are formed per hexose cleaved, and that two molecules of NAD+ are converted to NADH in the process. 

Fructose-1,6-bisphosphate is cleaved by aldolase into two molecules of triose phosphate. This reaction represents the reversal of an aldol condensation (fig. 12.20). Most aldolases are highly specific for the upper end of the substrate molecule, requiring a phosphate group at C-l, a carbonyl at C-2, and specific steric configurations at C-3 and C-4. The nature of the remainder of the molecule is unimportant as far as the enzyme action is concerned. 

In the following stage, fructose-6-phosphate is phosphorylated again by the action of phosphofructokinase to form fructose-1,6-diphosphate. This reaction also consumes ATP. Later, the enzyme aldolase cleaves to fructose-6-phosphate. As a result of this reaction two triose phosphates are formed dihydroxyacetone phosphate and glyceraldehyde-3-phosphate. This reaction produces a much greater proportion of dihydroxyacetone phosphate (96%), which is rapidly transformed into glycer-aldehyde-3-phosphateby triose phosphate isomerase (Heinisch and Rodicio 1996). 

Thus, two molecules of glyceraldehyde v4-phosphate are formed from one molecule of fructose 1,6-bisphosphate by the sequential action of aldolase and triose phosphate isomerase. The economy of metabolism is evident in this reaction sequence. The isomerase funnels dihydroxyacetone phosphate into the main glycolytic pathway a separate set of reactions is not needed. 

In the liver, kidney, and intestine, fructose can be converted to glycolytic/ gluconeogenic intermediates by the actions of three enzymes—fructokinase, aldolase B, and triokinase (also called triose kinase)—as shovra in Figure 24-1. In these tissues, fructose is rapidly phosphorylated to fructose 1-phosphate (FIP) by fructokinase at the expense of a molecule of adenosine triphosphate (ATP). This has the effect of trapping fructose inside the cell. A deficiency in this enzyme leads to the rare but benign condition known as essential fmcto-suria. In other tissues such as muscle, adipose, and red blood cells, hexokinase can phosphorylate fructose to the glycolytic intermediate fmctose 6-phosphate (F6P). 

FIP is formed by action of the enzyme fructokinase on fructose and ATP. FIP is subsequently broken down by aldolase B to dihydroxy acetone phosphate, a glycolytic intermediate, and D- hlO... 

Syringolide 2 (58), a bacterial signal molecule that elicits active defence in resistant plants, has been made (Scheme 11) from the protected ketose 57, itself prepared from D-arabinose (sugar carbons numbered) in nine steps. This sequence can be considerably shortened by use of a chemo-enzymatic approach, in which 57 was made in three steps by condensation of dihydroxyacetone phosphate with 0-Pmb-glycolaldehyde, catalysed by fructose 1,6-diphosphate aldolase, followed by action of phosphatase and formation of the isopropylidene derivative. ... 

Prepared by action of yeasts on Glucose, Sucrose and Fructose formed from Fructose 6-phosphate in the presence of Mg , ATP and the enzyme phosphohexokinase. Metabolic intermed. Cardioprotective agent. [a]o +4.04 (c, 13.6 in H2O). pK i 1.52 pAa2 6.31 (25°). Reversibly cleaved in the presence of Aldolase to give 3-Phos-phoglyceraldehyde and 1-Phosphodihy-droxyacetone... 

In photosynthesis, phosphoglyceric acid is reduced to glyceraldehyde 3-phosphate and the latter converted to fructose 1,6-diphosphate by the action of triose phosphate ison erase and aldolase (Fig. 3). An additional step, catalyzed by fructose diphosphatase, was... 

The second stage of glycolysis forms glycer-aldehyde 3-phosphate. Under the catalytic action of aldolase, fructose 1,6-biphosphate is cleaved thus forming two triose phosphate isomers ... 

Meyerhof, O., Lohmann, K., and Schuster, P., Biochem. Z., 286, 301, 319 (1936). It has recently been reported that the classical crystalline muscle aldolase has no action on fructose-l-phosphate. The reaction described in Fig. 1 is stated to be catalyzed by a 1-phosphofructaldosase found in liver. (Leuthardt, F., Testa, E., and Wolf, H. P., Heh. Chim. Acta 36, 227 (1953).)... 

Apparently, all DHAP aldolases are highly specific for the donor component 22 for mechanistic reasons [29]. For synthetic applications, two equivalents of 22 are conveniently generated in situ from commercial fructose 1,6-bisphosphate 23 by the combined action of FruA and triose phosphate isomerase (EC 5.3.1.1) [93,101]. The reverse, synthetic reaction can be utilized to prepare ketose bisphosphates, as has been demonstrated by an expeditious multienzymatic synthesis of the (3S,4S) all-cis-configurated D-tagatose 1,6-bisphosphate 24 (Fig. 13) from dihydroxyacetone 27, including a cofactor-dependent phosphorylation, by employing the purified TagA from E. coli (Fig. 13) [95,96]. 

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