Pentose phosphate pathway transaldolase

MORE NADPH THAN RmOSE-5-P IS NEEDED BY THE CELL Large amounts of N/VDPH can be supplied for biosynthesis without concomitant production of ribose-5-P, if ribose-5-P produced in the pentose phosphate pathway is recycled to produce glycolytic intermediates. As shown in Figure 23.39, this alternative involves a complex interplay between the transketolase and transaldolase reac-... 

One of the steps in the pentose phosphate pathway for glucose catabolism is the reaction of sedoheptulose 7-phosphate with glyceraldehyde 3-pho phate in the presence of a transaldolase to yield erythrose 4-phosphate and fructose 6-phosphate. 

Verhoeven NM, Huck JH, Roos B, Struys EA, Salomons GS, Douwes AC, van der Knaap MS, Jakobs C (2001) Transaldolase deficiency liver cirrhosis associated with a new inborn error in the pentose phosphate pathway. Am J Hum Genet 68 1086-1092... 

FIGURE 14-22 Nonoxidative reactions of the pentose phosphate pathway, (a) These reactions convert pentose phosphates to hexose phosphates, allowing the oxidative reactions (see Fig. 14-21) to continue. The enzymes transketolase and transaldolase are specific to this pathway the other enzymes also serve in the glycolytic or gluconeogenic pathways, (b) A schematic diagram showing the pathway... 

In the second phase, transaldolase (with TPP as cofactor) and transketolase catalyze the interconversion of three-, four-, five-, six-, and seven-carbon sugars, with the reversible conversion of six pentose phosphates to five hexose phosphates. In the carbon-assimilating reactions of photosynthesis, the same enzymes catalyze the reverse process, called the reductive pentose phosphate pathway conversion of five hexose phosphates to six pentose phosphates. 

Closely related to aldolases is transaldolase, an important enzyme in the pentose phosphate pathways of sugar metabolism and in photosynthesis. The mechanism of the transaldolase reaction (Eq. 17-15) is similar to that used by fructose-1,6-bisphosphate aldolase with a lysine side chain forming a Schiff base and catalytic aspartate and glutamate side chains.198... 

Two NADPH Molecules Are Generated by the Pentose Phosphate Pathway Transaldolase and Transketolase Catalyze the Interconversion of Many Phosphorylated Sugars Production of Ribose-5-phosphate and Xylulose-5-phosphate... 

Both transaldolase and transketolase require a ketose phosphate as the donor molecule and an aldose phosphate as the acceptor. Furthermore, both enzymes require the same steric configuration at carbons 3 and 4 as is found in glucose and fructose. Ribulose-5-phosphate, the first pentose phosphate to be formed in the pentose phosphate pathway, does not have the correct configuration to serve as a substrate for either transaldolase or transketolase. However, both a suitable donor ketose and an acceptor aldose can be made by isomerizations of ribulose-5-phosphate, and enzymes that... 

The transaldolase (EC 2.2.1.2) is an ubiquitous enzyme that is involved in the pentose phosphate pathway of carbohydrate metabolism. The class I lyase, which has been cloned from human [382] and microbial sources [383], transfers a dihydroxyacetone unit between several phosphorylated metabolites. Although yeast transaldolase is commercially available and several unphosphorylated aldehydes have been shown to be able to replace the acceptor component, preparative utilization has mostly been limited to microscale studies [384,385] because of the high enzyme costs and because of the fact that the equilibria usually are close to unity. Also, the stereochemistry of transaldolase products (e.g. 38, 40) [386] matches that of the products from the FruA-type DHAP aldolase which are more effortlessly obtained. 

The transketolase and transaldolase reactions are reversible and so allow either the conversion of ribose 5-phosphate into glycolytic intermediates when it is not needed for other cellular reactions, or the generation of ribose 5-phosphate from glycolytic intermediates when more is required. The rate of the pentose phosphate pathway is controlled by NADP+ regulation of the first step, catalyzed by glucose 6-phosphate dehydrogenase. 

Stage 3 - Linkage of the pentose phosphate pathway to glycolysis via trans-ketolase and transaldolase... 

If at any time only a little ribose 5-phosphate is required for nucleic acid synthesis and other synthetic reactions, it will tend to accumulate and is then converted to fructose 6-phosphate and glyceraldehyde 3-phosphate by the enzymes transketolase and transaldolase. These two products are intermediates of glycolysis. Therefore, these reactions provide a link between the pentose phosphate pathway and glycolysis. The outline reactions are shown below. 

Enzymatic Reaction Mechanisms II Biochemical reactions often look more complex than they really are. In the pentose phosphate pathway (Chapter 14), sedoheptulose 7-phosphate and glycer-aldehyde 3-phosphate react to form erythrose 4-phosphate and fructose 6-phosphate in a reaction catalyzed by transaldolase. 

Answer The reductive pentose phosphate pathway regenerates ribulose 1,5-bisphosphate from triose phosphates produced during photosynthesis, in a series of reactions involving sugars of three, four, five, six, and seven carbons and the enzymes transaldolase and transketo-lase. The oxidative pentose phosphate pathway plays a different metabolic role it provides NADPH for reductive biosynthesis and pentose phosphates for nucleotide synthesis. 

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. 

Figure 6.4. Role of transketolase in the pentose phosphate pathway. Glucose 6-phosphate dehydrogenase, EC 1.1.1.49 phosphogluconate dehydrogenase, EC 1.1.1.44 rihulose-phosphate epimerase, EC 5.1.3.1 phosphorihose isomerase, EC 5.3.1,6 transketolase, EC 2.2.1.1 and transaldolase, EC 2.2.I.2.

The preceding reactions yield two molecules of NADPH and one molecule of ribose 5-phosphate for each molecule of glucose 6-phosphate oxidized. However, many cells need NADPH for reductive biosyntheses much more than they need ribose 5-phosphate for incorporation into nucleotides and nucleic acids. In these cases, ribose 5-phosphate is converted into glyceraldehyde 3-phosphate and fructose 6-phosphate by transketolase and transaldolase. These enzymes create a reversible link between the pentose phosphate pathway and glycolysis by catalyzing these three successive reactions. 

Thus, the equivalent of glucose 6-phosphate can be completely oxidized to CO 2 with the concomitant generation of NADPH. In essence, ribose 5-phosphate produced by the pentose phosphate pathway is recycled into glucose 6-phosphate by transketolase, transaldolase, and some of the enzymes of the gluconeogenic pathway. 

Aldolase participates in the Calvin cycle, whereas transaldolase participates in the pentose phosphate pathway. 

E. In the first three reactions of the pentose phosphate pathway, glucose is converted to ribulose 5-phosphate and C02, with the production of NADPH. These reactions are not reversible. Ribose 5-phosphate and xylulose 5-phosphate may be formed from ribulose 5-phos-phate. A series of reactions catalyzed by transketolase and transaldolase produce the glycolytic intermediates fructose 6-phosphate and glyceraldehyde 3-phosphate. 

The Pentose Phosphate Pathway and Glycolysis Are Linked by Transketolase and Transaldolase... 

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