Glyceraldehyde 3-phosphate tautomerism

Reduction of the acyl phosphate gives glyceraldehyde 3-phosphate, which Q undergoes keto-enol tautomerization to yield dihydroxyacetone phosphate. 

Tautomerism occurs elsewhere in the glycolytic pathway (see Section 15.2). The transformation of glyceraldehyde 3-phosphate into dihydroxyacetone phosphate involves two such keto-enol tautomerisms, and... 

Both the aldol and reverse aldol reactions are encountered in carbohydrate metabolic pathways in biochemistry (see Chapter 15). In fact, one reversible transformation can be utilized in either carbohydrate biosynthesis or carbohydrate degradation, according to a cell s particular requirement. o-Fructose 1,6-diphosphate is produced during carbohydrate biosynthesis by an aldol reaction between dihydroxyacetone phosphate, which acts as the enolate anion nucleophile, and o-glyceraldehyde 3-phosphate, which acts as the carbonyl electrophile these two starting materials are also interconvertible through keto-enol tautomerism, as seen earlier (see Section 10.1). The biosynthetic reaction may be simplihed mechanistically as a standard mixed aldol reaction, where the nature of the substrates and their mode of coupling are dictated by the enzyme. The enzyme is actually called aldolase. 

Step 5 is an isomerization of dihydroxyacetone phosphate to glyceraldehyde 3-phosphate that occurs by keto-enol tautomerization. 

Enzyme mechanisms can often avoid high-energy, unstable cationic or anionic intermediates that increase the reaction barrier. Triosephosphate isomerase catalyzes the tautomerization of the achiral dihydroxy acetone phosphate (DHAP) to f -glyceraldehyde-3-phosphate (G3P) by the mechanism shown below. Not only does the push-pull mechanism avoid forming a highly basic enolate, but the binding mode of DHAP determines which face of the enediol will be protonated in the second step, and therefore... 

Butlerov found out that in alkaline medium (calcium hydroxide), formaldehyde HCHO polymerizes to form about 20 different sugars as racemic mixtures, Butlerov 1861. The reaction requires a divalent metal ion. Breslow found a detailed mechanism of reaction that explains the reaction products, (Breslow 1959). He found that glycol-aldehyde is the first product that is subsequently converted into glyceral-dehyde (a triose), di-hydroxy-acetone, and then into various other sugars, tetrose, pentose, and hexose. The formose reaction advances in an autocatalytic way in which the reaction product is itself the catalyst for that reaction with a long induction period. The intermediary steps proceed via aldol and retro-aldol condensations and, in addition, keto-enol tautomerizations. It remains unexplained how the phosphorylation of 3-glyceraldehyde leads to glycral-3-phosphate (Fig. 3.6). Future work should study whether or not ribozymes exist that can carry out this reaction in a stereo-specific way. 

Scheme 11.5. A cartoon representation of the catalyzed (fructose-bisphosphate aldolase, EC 4.1.2.13) aldol-type condensation between glyceraldehyde 3-phosphate and dihydroxyacetone monophosphate to produce the six-carbon ketosugar fructose-1,6-bisphosphate. An active site lysine Lys-NH2 [" H3NCH2CH2CH2CH2CH(NH3 )C02 ] apparently serves as the catalyst through addition at the carbonyl followed by proton tautomerization.

Scheme 102.3 reports the mevalonate-independent pathway, also named as deoxyxylulose (DXP) or methyl erythritol phosphate pathway. It starts from pyruvic acid and o-glyceraldehyde to form 1 -deoxy-o-xylulose 5P (DXP) reduced to 2 C-methyl-D-erythritol 4P which by phosphorylation affords a cyclic intermediate 2 C-methyl-D-erythritol 2,4-cyclophosphate. This compound by elimination reaction followed by tautomerization gives IPP and DMAPP, the latter possibly formed either independently or by isomerization. 

Tautomerism is important in the chemistry and metabohsm of carbohydrates (Chapter 26). For example, glyceraldehyde 3-phosphate and dihydroxyacetone phosphate are two intermediates in glycolysis, a metabohc pathway in almost all organisms. 

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