Dihydroxyacetone phosphate, glycolysis

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... 

Dihydroxyacetone phosphate is of course an intermediate in glycolysis. D-Gly-ceraldehyde can be phosphorylated by triose kinase in the presence of ATP to form D-glyceraldehyde-3-phosphate, another glycolytic intermediate. 

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).

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. 

Figure 17-2. The pathway of glycolysis. ( ,—P, HOPOj " .inhibition.) At asterisk Carbon atoms 1-3 of fructose bisphosphateform dihydroxyacetone phosphate, whereas carbons 4-6 form glyceraldehyde 3-phosphate. The term "bis-," as in bisphosphate, indicates that the phosphate groups are separated, whereas diphosphate, as in adenosine diphosphate, indicates that they are joined.

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-... 

Glycerol phosphate dehydrogenase (GPDH) is indirectly associated with glycolysis and reduces dihydroxyacetone phosphate to glycerol-3-phosphate, oxidizing NADH... 

Fatty acids are both stored in and exported from the liver as triglycerides. The carbon atoms for the glycerol backbone of triglycerides are also derived from glucose by a diversion of dihydroxyacetone phosphate from glycolysis (Figures 6.16 and 6.17). 

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

Glycerol 3-phosphate can arise in two ways, either (i) from glycerol, via the enzyme glycerol kinase or (ii) from dihydroxyacetone phosphate, which is produced in glycolysis, by reduction with NADH, catalysed by glycerol-3-phosphate dehydrogenase ... 

Triose phosphate isomerase is one of the enzymes of glycolysis (see Section 15.2) and is responsible for converting dihydroxyacetone phosphate into glyceraldehyde 3-phosphate by a two-stage enolization process. An intermediate enediol is involved - this common enol can revert to a keto form in two ways, thus providing the means of isomerization. 

Aldolase catalyses both aldol and reverse aldol reactions according to an organism s needs. In glycolysis, the substrate fmctose 1,6-diphosphate is cleaved by a reverse aldol reaction to provide one molecule of glyceraldehyde 3-phosphate and one molecule of dihydroxyacetone phosphate. In carbohydrate synthesis, these two compounds can be coupled in an aldol reaction to produce fmctose 1,6-diphosphate. 

A special ketohexokinase [1] initially phos-phorylates fructose into fructose 1-phosphate. This is then cleaved by an aldolase [2], which is also fructose-specific, to yield glycerone 3-phosphate (dihydroxyacetone phosphate) and glyceraldehyde. Glycerone 3-phosphate is already an intermediate of glycolysis (center), while glyceraldehyde can be phosphorylated into glyceraldehyde 3-phosphate by triokinase [3]. 

In addition to the cofactors ATP, NADH, and NADPH, hundreds of metabolic intermediates also must be present at appropriate concentrations in the cell. For example, the glycolytic intermediates dihydroxyacetone phosphate and 3-phosphoglycerate are precursors of tri-acylglycerols and serine, respectively. When these products are needed, the rate of glycolysis must be adjusted to provide them without reducing the glycolytic production of ATP. 

Summary of anaerobic glycolysis. Reactions involving the production or consumption of ATP or NADH are indicated. The irreversible reactions of glycolysis are shown with thick arrows. DHAP = dihydroxyacetone phosphate. 

Fate of glycerol Glycerol that is released from triacylglycerol used almost exclusively by the liver to produce glycerol 3-phc phate, which can enter either glycolysis or gluconeogenesis oxidation to dihydroxyacetone phosphate (see p. 188). 

The metabolic pool that consists of fructose-1,6-bisphosphate and the two triose phosphates—glyceralde-hyde-3-phosphate and dihydroxyacetone phosphate (DHAP)—is somewhat different from the other two pools of intermediates in glycolysis because of the nature of the chemical relationships between these compounds. In the other pools the relative concentrations of the component compounds at equilibrium are independent of the absolute concentrations. Because of the cleavage of one substrate into two products, the relative concentrations of fructose-1,6-bisphosphate and the triose phosphates are functions of the actual concentrations. For such reactions, the relative concentrations of the split products must increase with dilution. (For the reaction A v B + C, the equilibrium constant is equal to [B][C]/[A], If the concentration of A decreases, for example, by a factor of 4, equilibrium is... 

The isomeric triose phosphates, glyceraldehyde-3-phos-phate and dihydroxyacetone phosphate, bear the same relationship to each other as do glucose-6-phosphate and fruc-tose-6-phosphate. Their interconversion, catalyzed by triose phosphate isomerase, is equally facile (see fig. 12.13). Dihydroxyacetone phosphate is a starting material for the synthesis of the glycerol moiety of fats (chapter 19), but only glyceraldehyde-3-phosphate is used in glycolysis. Thus, under ordinary circumstances nearly all of the dihydroxyacetone phosphate that is formed in the cleavage of... 

In the first phase of phospholipid synthesis from glyc-erol-3-phosphate to phosphatidic acid, the pathways in E. coli and eukaryotes are very similar (see fig. 19.2). The major difference is that one additional pathway exists for generation of phosphatidic acid from dihydroxyacetone phosphate, an intermediate in glycolysis. Once phosphatidic acid is made, it is rapidly converted to diacylglycerol or CDP-diacylglycerol (see fig. 19.2) both of which are intermediates for the biosynthesis of eukaryotic phospholipids. 

Aldolases such as fructose-1,6-bisphosphate aldolase (FBP-aldolase), a crucial enzyme in glycolysis, catalyze the formation of carbon-carbon bonds, a critical process for the synthesis of complex biological molecules. FBP-aldolase catalyzes the reversible condensation of dihydroxyacetone phosphate (DHAP) and glyceralde-hyde-3-phosphate (G3P) to form fructose-1,6-bisphosphate. There are two classes of aldolases the first, such as the mammalian FBP-aldolase, uses an active-site lysine to form a Schiff base, whereas the second class features an active-site zinc ion to perform the same reaction. Acetoacetate decarboxylase, an example of the second class, catalyzes the decarboxylation of /3-keto acids. A lysine residue is required for good activity of the enzyme the -amine of lysine activates the substrate carbonyl group by forming a Schiff base. 

Breakdown The fatty acids in triacylglycerols are released from the glycerol backbone by the action of lipases. The free fatty acids can then be degraded by (3-oxidation to produce energy. The glycerol is converted into dihydroxyacetone phosphate which enters glycolysis. 

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