Phosphate dihydroxyacetone 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]. 

Figure 3 A possible mechanism for the isomerization of dihydroxyacetone phosphate (DHAP) to D glyceraldehyde 3 phosphate (GAP) by the enzyme triosephosphate isomerase (TIM). The general acid (Glu 165) and general base (His 95) are shown.

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. 

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

Step 4 of Figure 29.7 Cleavage Fructose 1,6-bisphosphate is cleaved in step 4 into two 3-carbon pieces, dihydroxyacetone phosphate (DHAP) and glyceraldehvde 3-phosphate (GAP). The bond between C3 and C4 of fructose 1,6-bisphosphate... 

Due to mechanistic requirements, most of these enzymes are quite specific for the nucleophilic component, which most often is dihydroxyacetone phosphate (DHAP, 3-hydroxy-2-ox-opropyl phosphate) or pyruvate (2-oxopropanoate), while they allow a reasonable variation of the electrophile, which usually is an aldehyde. Activation of the donor substrate by stereospecific deprotonation is either achieved via imine/enamine formation (type 1 aldolases) or via transition metal ion induced enolization (type 2 aldolases mostly Zn2 )2. The approach of the aldol acceptor occurs stereospecifically following an overall retention mechanism, while facial differentiation of the aldehyde is responsible for the relative stereoselectivity. 

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]. 

Tracing the carbons of glucose to pyruvate gets complicated when fructose 1,6-bisphosphate (FBP) is cleaved into two 3-carbon fragments, glyceraldehyde 3-phosphate (G3P) and dihydroxyacetone phosphate (DHAP). The numbers of the original carbons of glucose are indicated by the superscripts next to the carbon. 

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). 

There is only one compound which carries an aldehyde group, so glyceraldehyde-3-P must be compound (viii) and acetone you may already know as a ketone, so compound (ii) is dihydroxyacetone phosphate, DHAP. 

Dihydroxyacetone phosphate (DHAP) is used in liver and adipose tissue for triglyceride synthesis. 

Reduction of dihydroxyacetone phosphate (DHAP) from glycolysis by glycerol 3-P dehydrogenase, an enzyme in both adipose tissue and liver... 

Glycerol may be picked up by liver and converted to dihydroxyacetone phosphate (DHAP) for gluconeogenesis, and the fetty adds are distributed to tissues that can use them. Free fatty acids are transported through the blood in association with serum albumin. 

The main group of aldolases from the biocatalytic point of view is, arguably, the one that uses dihydroxyacetone phosphate (DHAP) as donor. Here, we will concentrate on that appHcations in which DHAP-dependent aldolase are part of a multi-enzyme system or, alternatively, on those in which the aldolase-catalyzed reaction is key in a multi-step synthetic pathway. 

With respect to practical applications in asymmetric synthesis, the four stereo-chemically distinct dihydroxyacetone phosphate (DHAP, 1)-dependent enzymes had been particularly appealing to us because these enzymes control the creation of two new asymmetric centers at the termini of a newly formed C-C bond, thus allowing an effective stereocombinatorial synthesis of stereoisomers (Scheme 2.2.5.1) [1, 3]. The individual aldolases are involved in the reversible cleavage of... 

Alkyl-dihydroxyacetone phosphate (DHAP) synthase Isolated alkyl-DHAP synthase deficiency... 

FIGURE 21-21 Glyceroneogenesis. The pathway is essentially an abbreviated version of gluconeogenesis, from pyruvate to dihydroxyacetone phosphate (DHAP), followed by conversion of DHAP to glycerol 3-phosphate, which is used for the synthesis of triacylglycerol. 

The probable reaction mechanism of triosephosphate isomerase. The y-carboxylate group of Glu 165 acts as a general base to remove a proton from C-l of the substrate, dihydroxyacetone phosphate (DHAP). This generates a planar ene-diolate intermediate that has two... 

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