Dihydroxyacetone phosphate, role

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. 

Stable isotope-labelled intermediates playing an important role in the study of the mevalonate as well as the deoxyxylulose phosphate pathway of isoprenoid biosynthesis have been prepared. C- and " C-labelled 4-diphosphacytidyl-2C-methyl-D-erythrytol (52) and 2C-methyl-D-erythrytol-4-phosphate (53) have been obtained in milimol quantity and in high yield by sequences of one-pot reactions using C-labelled pyruvate, or dihydroxyacetone phosphate... 

Fig. 4. Ether phospholipid synthesis from dihydroxyacetone-phosphate. (A) Dihydroxyacetone-P acyl transferase (DHAPAT). The first step of ether phospholipid synthesis is catalyzed by peroxisomal DHAPAT. This enzyme is a required component of complex ether lipid biosynthesis and its role cannot be assumed by a cytosolic enzyme that also forms acyldihydroxyacetone-P. (B) Ether bond formation by alkyl-DHAP synthase. The reaction that forms the 0-alkyl bond is catalyzed by alkyl-DHAP synthase and is thought to proceed via a ping-pong mechanism. Upon binding of acyl-DHAP to the enzyme alkyl-DHAP synthase, the pro-f hydrogen at carbon atom 1 is exchanged by enolization of the ketone, followed by release of the acyl moiety to form an activated enzyme-DHAP complex. The carbon atom at the 1-position of DHAP in the enzyme complex is thought to carry a positive charge that may be stabilized by an essential sulfhydryl group of the enzyme thus, the incoming alkox-ide ion reacts with carbon atom 1 to form the ether bond of alkyl-DHAP. It has been proposed that a nucleophilic cofactor at the active site covalently binds the DHAP portion of the substrate.

The role of enediols in the conversion of L-glyceraldehyde 3-phosphate (26) into either dihydroxyacetone phosphate (27) or inorganic phosphate plus methylglyoxal (28) has been postulated for some time. Triose phosphate isomerase, which does not react with (26) directly, can convert it into dihydroxyacetone phosphate by... 

Describe the lipolysis of triacylglycerols by lipases. Explain the role of cyclic AMP in the regulation of lipase in adipose cells. Appreciate that serum albumin carries the fatty acids from the adipocyte to other tissues. Outline the conversion of glycerol to glycerol 3-phosphate and dihydroxyacetone phosphate. 

Mn-SOD is an important antioxidant enzyme for the cell due to its role in detoxifying the free radical species superoxide (Oj), so HNE modification of this protein makes the cell more vulnerable to free radical attack. Alpha enolase facilitates the penultimate step of glycolysis by catalyzing the conversion of 2-phosphoglycerate into phosphoenolpyruvate. With HNE modification of alpha enolase, the cell is at risk of inadequate ATP stores due to inhibited production of pyruvate for fueling the citric acid cycle. Similarly, HNE modification of ATPase can lead to inhibited ATP formation due to the direct role of this enzyme in ATP synthesis. Triose phosphate isomerase catalyzes the reversible conversion of dihydroxyacetone phosphate to glyceraldehyde-3-phosphate in glycolysis and MDH catalyzes the oxidation of malate to oxaloacetate, so HNE modification of these proteins can also lead to lower ATP production. 

Dihydroxyacetone phosphate is converted catalyti-cally to L-a-glycerophosphate under the influence of glycerophosphate dehydrogenases, of which there are at least two. One is found in the soluble fraction of muscle homogenates it has been crystallized and experiments have shown that the enzyme molecule contains NAD. The role of this enzyme has been clarified. Most of the original studies were done on insect... 

Although not completely known, the amino acid sequence of the rabbit muscle aldolase subunit is largely elucidated. (A more detailed description on protein structure appears in the chapter on inborn errors of metabolism.) The molecule contains 364 amino acids with a proline NH2-terminal, a tyrosine in the COOH-terminal position, and 8 cysteine residues. A critical residue is the lysine 221 which is believed to form a Schiff base with dihydroxyacetone phosphate. (The role of Schiff bases in enzymic reactions is discussed in more detail in the section devoted to transaminases.) In the model proposed by Lai und Horecker [51], this lysine is near the center of the molecule. If one follows the contour of the molecule from this critical residue 221, which must be at the active center, toward the tyrosine carboxy terminal, three SH groups are well exposed on the surface of the molecule. They occupy positions 193, 171, and 143. 

Iterative Strategy for the Synthesis of Polyacetates Enders identified 2,2-dimethyl-l,3-dioxan-5-one 12 [15] as a particularly interesting building block for the synthesis of polyacetates using the SAMP/RAMP hydrazone sbategy [16]. Indeed, this building block can play the role of a synthetic equivalent of dihydroxyacetone phosphate (DH AP)... 

Finally, several other animal tissues yield useful enzymes that have been employed in S5mthesis. Pepsin is an important digestive protease from animal stomach whose native role is hydrolyzing amide bonds involving hydrophobic, aromatic amino adds, for example, phenylalanine, tyrosine, and tryptophan. Acylase from pordne kidney sdectivdy hydrolyzes N-acetyl amino adds and is commercially available. It has long been used for kinetic resolutions of amino adds. In addition to hydrolases, other animal enzymes have found important applications in biocatalysis. Rabbit musde aldolase is commerdally awiilable and was shown to catalyze aldol condensations between dihydroxyacetone phosphate and various nonnatural aldehydes by the Whitesides group in 1989 [10]. This seminal report touched off an avalanche of new applications for this and related enzymes in asymmetric synthesis. 

We have traced the metabolic pathways channelling metabolites towards the fluorometabolites in S. cattleya and an overview of these relationships is shown in Figure 13. We believe that the substrate for the fluorination process is either a C3 phosphorylated glycolytic intermediate such as dihydroxyacetone phosphate or glyceraldehyde-3-phosphate, or alternatively a C2 metabolite such glycoaldehyde phosphate, derived from these compounds. Fluoroacetaldehyde appears to be a strong candidate for the role of common intermediate to both fluoroacetate and 4-fluorothreonine. 

Heating of dihydroxyacetone in the presence of phosphate ions in known to produce substantial amounts of pyruvaldehyde (10). Furthermore pyruvaldehyde is assumed to catalyze the formation of 1-pyrro-line by Strecker degradation of proline (11). To study the role of 1-pyrroline and pyruvaldehyde in Acp formation, three additional experiments were conducted. 

In the actual cleavage reaction of glycolysis, D-fructose< 1,6-diphosphate is converted into D-glyceraldehyde-3-phosphate and dihydroxyacetone, CH2OHCOCH2OH. What kind of reaction is this, basically Sketch out a possible mechanism, neglecting, of course, the all-important role of the enzyme. (Hints The enzyme required is called aldolase. See Problem 21.14, p. 711.)... 

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