Pentose phosphate pathway nonoxidative phase

Figure 6-3. The pentose phosphate pathway. In the oxidative phase of the pentose phosphate pathway, NADP is reduced to NADPH H, with feedback regulation by NADPH at the step catalyzed by glucose 6-phosphate dehydrogenase. In the nonoxidative phase, multiple sugar interconversions catalyzed by three different enzymes occur.

The five E. coli genes inserted in Z. mobilis allowed the entry of arabinose into the nonoxidative phase of the pentose phosphate pathway (Fig. 14-22), where it was converted to glucose 6-phosphate and fermented to ethanol. 

The pentose phosphate pathway meets the need of all organisms for a source of NADPH to use in reductive biosynthesis (Table 20.2). This pathway consists of two phases the oxidative generation of NADPH and the nonoxidative interconversion of sugars (Figure 20.19). In the oxidative phase, NADPH is generated when glucose 6-phosphate is oxidized to ribose 5-phosphate. This five-carbon sugar and its derivatives are components of RNA and DNA, as well as ATP, NADH, FAD, and coenzyme A. 

Figure 20.19. Pentose Phosphate Pathway. The pathway consists of (1) an oxidative phase that generates NADPH and (2) a nonoxidative phase that interconverts phosphorylated sugars.

Nonoxidative phase of the pentose phosphate pathway. Numbers in parentheses show the distribution of carbon atoms between the various branches of each reaction. TK = transketolase GAP = glyceraldehyde 3-phosphate DHAP = dihydroxyacetone phosphate P = phosphate. 

Glycolysis. Ribose 5-phosphate can also be produced from intermediates of glycolysis (Figure 27-6). The enzymes involved are those of the nonoxidative phase of the pentose phosphate pathway, that occur in many tissues. 

The pentose phosphate pathway is an alternative metabolic pathway for glucose oxidation in which no ATP is generated. Its principal products are NADPH, a reducing agent required in several anabolic processes, and ribose-5-phosphate, a structural component of nucleotides and nucleic acids. The pentose phosphate pathway occurs in the cytoplasm in two phases oxidative and nonoxidative. In the oxidative phase of the pathway, the conversion of glucose-6-phosphate to ribu-lose-5-phosphate is accompanied by the production of two molecules of NADPH. 

If the cell requires more NADPH than ribose molecules, it can channel the products of the nonoxidative phase of the pentose phosphate pathway into glycolysis. As this overview of the two pathways illustrates, excess ribose-5-phos-phate can be converted into the glycolytic intermediates fructose-6-phosphate and glyceraldehyde-3-phosphate. 

The pentose phosphate pathway, in which glucose-6-phos-phate is oxidized, occurs in two phases. In the oxidative phase, two molecules of NADPH are produced as glucose-6-phosphate is converted to ribulose-5-phosphate. In the nonoxidative phase, ribose-5-phosphate and other sugars are synthesized. If cells need more NADPH than ribose-5-phos-phate, a component of nucleotides and the nucleic acids, then metabolites of the nonoxidative phase are converted into glycolytic intermediates. 

Later we shall see which solution has been adopted by living organisms for the equivalent biochemical problem, but before we can do this we need to see how the problem as I have presented it relates to the pentose phosphate pathway. This consists of both oxidative and nonoxidative phases, but we shall consider only the nonoxidative phase, which involves exchanging the carbon atoms of sugars so as to transform six pentose molecules into five hexose molecules, that is, to convert 6C5 into 5C6. The exchanges are brought about by enzymes that transfer a certain number of carbon atoms from one sugar to another. The mechanisms available to the cell are the transfer of two carbon... 

List the two phases of the pentose phosphate pathway (oxidative generation of NADPH and nonoxidative interconversion of sugars). List the biochemical pathways that require NADPH from the pentose phosphate pathway. 

Transketolase (TK) is involved in anaerobic carbohydrate metabolisms such as the nonoxidative phase of the pentose phosphate pathway. In plants and photosynthetic bacteria, TK is involved in the Calvin-Benson cycle. TK catalyses the transfer of a 2-carbon dihydroxyethyl group from a ketose phosphate (donor substrate such as D-xylulose 5-phosphate) to the Cl position of an aldose phosphate (acceptor substrate such as o-ribose 5-phosphate) (Figure 4.3) (Schneider and Lindqvist 1998). The first product is an aldose phosphate released from the donor (such as glyceraldehyde 3-phosphate) and the second is a ketose phosphate (such as sedoheptulose 7-phosphate), in which the 2-carbon fragment is attached to the acceptor. Examples of the substrates and the products mentioned above are for the first reaction of the pentose phosphate pathway. In the second reaction of the same pathway, the acceptor is D-ery-throse 4-phosphate and the second product is o-fructose 6-phosphate. A snapshot X-ray crystallographic study revealed that an ot-carbanion/enamine a,p-dihydroxyethyl ThDP is formed as a key intermediate (Fiedler et al. 2002). Then, a nucleophilic attack of the a-carbanion intermediate on the acceptor substrate occurs. 

In tissues that require primarily NADPH, the pentose phosphates produced in the oxidative phase of the pathway are recycled into glucose 6-phosphate. In this nonoxidative phase, ribulose 5-phosphate is first epimerized to xylulose 5-phosphate ... 

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