1.3- Dihydroxyacetone phosphate, reactions

FIGURE 20-10 Third stage of C02 assimilation. This schematic diagram shows the interconversions of triose phosphates and pentose phosphates. Black dots represent the number of carbons in each compound. The starting materials are glyceraldehyde 3-phosphate and dihydroxyacetone phosphate. Reactions catalyzed by transaldolase ( and ) and transketolase ((3) and ) produce pentose phosphates that are converted to ribulose 1,5-bisphosphate—ribose... 

Stereospecifidly of Dihydroxyacetone Phosphate Reactions. In both the aldolase and triose phosphate isomerase reactions a carbon-hydrogen bond of the hydroxymethyl group is broken. Isotope exchange experiments with tritium have shown that both enzymes catalyze an equilibration between one hydrogen of the substrate and the hydrogen of water. ° The two enzymes do not attack the same hydrogen atom each is specific for only one position. In the projection shown (XII),... 

Phospho-D-glyceraldehyde is isomerized by triose phosphate isomerase to dihydroxyacetone phosphate (reaction 6). The two trioses, 3-phospho-D-glycer-aldehyde and dihydroxyacetone phosphate, are then condensed together in a aldol-type condensation, catalyzed by aldolase to give D-fructose-l,6-bisphos-phate (reaction 7). This is a key intermediate in the photosynthetic process for the formation of many other carbohydrates, including D-glucose (see Fig. 10.5). 

Further steps m glycolysis use the d glyceraldehyde 3 phosphate formed m the aldolase catalyzed cleavage reaction as a substrate Its coproduct dihydroxyacetone phosphate is not wasted however The enzyme triose phosphate isomerase converts dihydroxyacetone phosphate to d glyceraldehyde 3 phosphate which enters the glycol ysis pathway for further transformations... 

There are two distinct groups of aldolases. Type I aldolases, found in higher plants and animals, require no metal cofactor and catalyze aldol addition via Schiff base formation between the lysiae S-amino group of the enzyme and a carbonyl group of the substrate. Class II aldolases are found primarily ia microorganisms and utilize a divalent ziac to activate the electrophilic component of the reaction. The most studied aldolases are fmctose-1,6-diphosphate (FDP) enzymes from rabbit muscle, rabbit muscle adolase (RAMA), and a Zn " -containing aldolase from E. coli. In vivo these enzymes catalyze the reversible reaction of D-glyceraldehyde-3-phosphate [591-57-1] (G-3-P) and dihydroxyacetone phosphate [57-04-5] (DHAP). 

The chemical reaction catalyzed by triosephosphate isomerase (TIM) was the first application of the QM-MM method in CHARMM to the smdy of enzyme catalysis [26]. The study calculated an energy pathway for the reaction in the enzyme and decomposed the energetics into specific contributions from each of the residues of the enzyme. TIM catalyzes the interconversion of dihydroxyacetone phosphate (DHAP) and D-glyceraldehyde 3-phosphate (GAP) as part of the glycolytic pathway. Extensive experimental studies have been performed on TIM, and it has been proposed that Glu-165 acts as a base for deprotonation of DHAP and that His-95 acts as an acid to protonate the carbonyl oxygen of DHAP, forming an enediolate (see Fig. 3) [58]. 

A non-linear regression analysis is employed using die Solver in Microsoft Excel spreadsheet to determine die values of and in die following examples. Example 1-5 (Chapter 1) involves the enzymatic reaction in the conversion of urea to ammonia and carbon dioxide and Example 11-1 deals with the interconversion of D-glyceraldehyde 3-Phosphate and dihydroxyacetone phosphate. The Solver (EXAMPLEll-l.xls and EXAMPLEll-3.xls) uses the Michaehs-Menten (MM) formula to compute v i- The residual sums of squares between Vg(,j, and v j is then calculated. Using guessed values of and the Solver uses a search optimization technique to determine MM parameters. The values of and in Example 11-1 are ... 

The fatty acids released on triacylglycerol hydrolysis are transported to mitochondria and degraded to acetyl CoA, while the glycerol is carried to the liver for further metabolism. In the liver, glycerol is first phosphorylated by reaction with ATP. Oxidation by NAD+ then yields dihydroxyacetone phosphate (DHAP), which enters the carbohydrate metabolic pathway. We ll discuss this carbohydrate pathway in more detail in Section 29.5. 

Step 3 of Figure 29.3 Alcohol Oxidation The /3-hydroxyacyl CoA from step 2 is oxidized to a /3-ketoacyl CoA in a reaction catalyzed by one of a family of L-3-hydroxyacyl-CoA dehydrogenases, which differ in substrate specificity according to the chain length of the acyl group. As in the oxidation of sn-glycerol 3-phosphate to dihydroxyacetone phosphate mentioned at the end of Section 29.2, this alcohol oxidation requires NAD+ as a coenzyme and yields reduced NADH/H+ as by-product. Deprotonation of the hydroxyl group is carried out by a histidine residue at the active site. 

Fructose 1,6-bisphosphate undergoes ring opening and is cleaved by a retro-aldol reaction into glyceraldehyde 3-phosphate and dihydroxyacetone phosphate (DHAP). 

Glyceraldehyde 3-phosphate and dihydroxyacetone phosphate join together in an aldol reaction to give fructose 1.6-bisphosphate. 

Figure 10.13 Aldol reactions catalyzed in vivo by the four stereocomplementary dihydroxyacetone phosphate-dependent aldolases.

Figure 10.19 Oxidative enzymatic generation of dihydroxyacetone phosphate in situ for stereoselective aldol reactions using DHAP aldolases (a), and extension by pH-controlled, integrated precursor preparation and product liberation (b).

This reaction is followed by another phosphorylation with ATP catalyzed by the enzyme phosphofructoki-nase (phosphofructokinase-1), forming fructose 1,6-bisphosphate. The phosphofructokinase reaction may be considered to be functionally irreversible under physiologic conditions it is both inducible and subject to allosteric regulation and has a major role in regulating the rate of glycolysis. Fructose 1,6-bisphosphate is cleaved by aldolase (fructose 1,6-bisphosphate aldolase) into two triose phosphates, glyceraldehyde 3-phosphate and dihydroxyacetone phosphate. Glyceraldehyde 3-phosphate and dihydroxyacetone phosphate are inter-converted by the enzyme phosphotriose isomerase. 

A tandem enzymatic aldol-intramolecular Homer-Wadsworth-Emmons reaction has been used in the synthesis of a cyclitol.310 The key steps are illustrated in Scheme 8.33. The phosphonate aldehyde was condensed with dihydroxyacetone phosphate (DHAP) in water with FDP aldolase to give the aldol adduct, which cyclizes with an intramolecular Horner-Wadsworth-Emmons reaction to give the cyclo-pentene product. The one-pot reaction takes place in aqueous solution at slightly acidic (pH 6.1-6.8) conditions. The aqueous Wittig-type reaction has also been investigated in DNA-templated synthesis.311... 

Aldolases catalyze asymmetric aldol reactions via either Schiff base formation (type I aldolase) or activation by Zn2+ (type II aldolase) (Figure 1.16). The most common natural donors of aldoalses are dihydroxyacetone phosphate (DHAP), pyruvate/phosphoenolpyruvate (PEP), acetaldehyde and glycine (Figure 1.17) [71], When acetaldehyde is used as the donor, 2-deoxyribose-5-phosphate aldolases (DERAs) are able to catalyze a sequential aldol reaction to form 2,4-didexoyhexoses [72,73]. Aldolases have been used to synthesize a variety of carbohydrates and derivatives, such as azasugars, cyclitols and densely functionalized chiral linear or cyclic molecules [74,75]. 

Jack-bean aldolase and liver aldolase catalyze the conversion of one mole of D-fructose 1-phosphate into one mole each of dihydroxyacetone phosphate and D-glycerose, and the reaction is reversible.73-77... 

L-Galactose is probably not produced from L-glycerose, since the latter inhibits glycolysis and, even so, reaction with dihydroxyacetone phosphate in the presence of aldolase yields L-sorbose 1-phosphate which, on stereochemical grounds, is also an unlikely precursor. A more plausible route is direct conversion from D-galactose (XXI) by complete reversal of stereo-... 

The enzyme also catalyzes the reversible reaction of dihydroxyacetone phosphate with D-erythrose 4-phosphate to produce D-oZ[Pg.218]

Recently, a chemoenzimatic catalized Henry reaction has been reported by El Blidi et al.53 Nitroaldol cyclization between the masked 3-hydroxy-4-nitrobutyraldehyde 72 and dihydroxyacetone phosphate (DHAP) 73, catalyzed by fructose-1,6-biphosphate aldolase (RAMA), afforded the nitro-cyclohexane 74 (Scheme 24). 

The natural substrate for the dehydrogenase, glyceraldehyde-3-phosphate (G-3-P), had been synthesized earlier by Hermann Fischer, Emil Fischer s son, and Baer in 1932. In 1934 Meyerhof and Lohmann synthesized hexose diphosphate, establishing it to be fructose 1,6 bisphosphate (F-l, 6 bis P). With F-1,6 bisP as substrate and hydrazine to trap the aldehydic and ketonic products of the reaction, G-3-P was identified in the mixture of G-3-P and dihydroxyacetone phosphate which resulted. Triose phosphate isomerase was then isolated and the importance of phosphorylated 3C derivatives established. 

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