G3P, glyceraldehyde-3-phosphate

Fig. 10.1 Cellular formation and metabolism of methylglyoxal (MG). AGEs advanced glycoxida-tion endproducts DHAP dihydroxyacetone phosphate G3P glyceraldehyde 3-phosphate F-6P fructose 6-phosphate F-1,6P2 fmctose 1,6-bisphosphate Gly-I II glyoxalase I II SSAO semicarbazide-sensitive amine oxidase AMO amine oxidase.

Fig. 15.3 Summary of strategies used to increase CoQlO production in microbes. Numbers in parentheses refer to studies listed in Tables 15.1 and 15.2. Abbreviations GLU glucose, NADPH/ NADP nicotinamide adenine dinucleotide phosphate, NADH/NAD nicotinamide adenine dinucleotide, G3P glyceraldehydes-3-phosphate, PYR pyruvate, A-CoA acetyl coenzyme A, TCA tricarboxylic acid, E4P erythrose-4-phosphate, PEP phosphoenolpyruvate, DMAPP demethylallyl diphosphate, IPP isopentenyl diphosphate, FPP farnesyl diphosphate, DPP decaprenyl diphosphate, PHBpara-hydroxybenzoate, NADH dh NADH dehydrogenase, succ. dh succinate dehydrogenase, ROS reactive oxygen species...

D-glyceraldehyde-3-phosphate, pyruvate (G3P) l-deoxy-D-xylulose-5-phosphate (DXP) 2C-methyl-D-erythritol-4-phosphate (MEP) 4-diphosph-2C-methyl-D-erythritol (CDP-ME) 4-diphosphocytidyl-2C-methyl-D-erythritol-2-phophate (CDP-MEP)... 

Clavulanic acid is synthesized by the condensation of L-arginine and D-glyceraldehyde-3-phosphate (G3P) as the first step [75,77] (Figure 12.2). A series of experiments revealed that the synthesis of clavulanic acid was limited by the availability of the C3 precursor, resulting from the species s limited ability to assimilate glucose [78]. Thus, the enhancement of clavulanic acid production requires alleviation of competition from other pathways for a C3 precursor [79]. 

There are two distinct pathways for biosynthesis of the IPP and DMAPP the mevalonate (MVA) pathway and the DXP pathway (Figure 12.3). The MVA pathway functions primarily in eukaryotes, while the DXP pathway is typically present in prokaryotes and the plastids of plants [90,91]. The first reaction in the DXP pathway is the condensation of pyruvate and D-glyceraldehyde-3-phosphate (G3P) to form DXP, which is catalyzed by DXP synthase encoded by the gene dxs [92]. In the second step, DXP is reduced to 2-C-methyl-D-erythritol-4-phosphate (MEP) by DXP reductoisomerase, which is encoded by the gene dxr (ispC) in E. coli. An array of other enzymes encoded by is pi), ispE, ispF, ispG, and ispH act in subsequent sequential reactions, leading to the conversion of MEP to IPP and DMAPP, which are interconverted by the enzyme encoded by idi [93-97],... 

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. 

Figure 6.3 Multienzymatic activity test for FSA. G3P D-glyceraldehyde-3-phosphate F6P fructose-6-phosphate PGI phosphoglucose Isomerase G6P glucose-6-phosphate GPD glu-cose-6-phosphate dehydrogenase.

There are two aspects to this process (a) the oxidation and subsequent phosphorylation of glyceraldehyde-3-phosphate (G3P) to 1,3-bisphospho-glycerate (1,3-BGP), and (b) the reduction of nicotinamide adenine dinucleotide (NAD+) to its reduced form designated as NADH. The net reaction can be written as... 

The preparation of DHAP for synthetic applications has been accomplished both enzymatically and chemically (Scheme 5.7).27 DHAP can be generated enzymatically in situ from fructose 1,6-diphosphate, using FDP aldolase acting in its catabolic mode, and triosephosphate isomerase (TPI). Glyceraldehyde 3-phosphate (G3P) and DHAP are produced in this reaction, with the G3P rapidly undergoing isomerization to DHAP. 

Like transketolase, transaldolase (TA, E.C. 2.2.1.2) is an enzyme in the oxidative pentose phosphate pathway. TA is a class one lyase that operates through a Schiff-base intermediate and catalyzes the transfer of the C(l)-C(3) aldol unit from D-sedoheptulose 7-phosphate to glyceraldehyde-3-phosphate (G3P) to produce D-Fru 6-P and D-erythrose 4-phosphate (Scheme 5.59). TA from human as well as microbial sources have been cloned.110 111 The crystal structure of the E. coliu and human112 transaldolases have been reported and its similarity to the aldolases is apparent, since it consists of an eight-stranded (o /(3)s or TIM barrel domain as is common to the aldolases. As well, the active site lysine residue that forms a Schiff base with the substrate was identified.14112 Thus, both structurally and mechanistically it is related to the type I class of aldolases. 

Scheme 5.59. Transaldolase catalyzed the transfer of the C1-C3 aldol unit of D-sedoheptulose-7-phosphate to D-glyceraldehyde-3-phosphate (G3P) generating D-fructose-6-phosphate and D-erythrose 4-phosphate. P = P032. ...

PG = 3-phosphoglyceric acid G3P = glyceraldehyde 3-phosphatc DHAP = dihydroxyacetone phosphate FDP = fructose 1,6-diphosphate F6P = fructose 6-phosphate G6P = glucose 6-phosphate E4P = erythrose 4-phosphate X5P = xylulose 5-phosphate SDP = sedoheptulose 1,7-diphosphaie S7P = sedoheptulose 7-phosphate R5P = ribose 5-phosphate Ru5P = ribulose 5-phosphate RuDP = ribulose 1,5-diphosphate... 

Fructose-1,6-diphosphate (FDP) aldolase catalyzes the reversible aldol addition of DHAP and D-glyceraldehyde-3-phosphate (G3P) to form D-fructose-1,6-diphosphate (FDP), for which eq 10 M in favor of FDP formation (Scheme 13.9). RAMA accepts a wide range of aldehyde acceptor substrates with DHAP as the donor to stereospecifically generate 3S,4S vicinal diols (Scheme 13.8). The diastereoselectivity exhibited by FDP aldolase depends on the reaction conditions. Racemic mixtures of non-natural aldehyde acceptors can be partially resolved only under conditions of kinetic control. When six-membered hemiacetals can be formed, racemic mixtures of aldehydes can be resolved under conditions of thermodynamic control (Scheme 13.10). 

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... 

Triose phosphate isomerase was the subject of a series of elegant and comprehensive isotope exchange experiments, which led to the establishment of the complete free energy profile for the catalysed reaction. In the following discussion, glyceraldehyde 3-phosphate will be abbreviated to G3P, dihydroxyacetone phosphate to DHAP and the enediolate to INT. The enzyme complexes and transition states will be denoted as in Figure 6.7. Reference to one of... 

The values of the pK s of the dihydroxyacetone phosphate (DHAP) substrate and the glyceraldehyde 3-phosphate (G3P) product for the TIM-catalyzed reaction are estimated as 18 and 20, respectively [2]. Knowles established the importance of... 

Regardless of the AG" for a particular biochemical reaction, it will proceed spontaneously within cells only if AG is negative, given the usual intracellular concentrations of reactants and products. For example, the conversion of glyceraldehyde 3-phosphate (G3P) to dihydroxyacetone phosphate (DHAP), two Intermediates in the breakdown of glucose,... 

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