Nonoxidative phase

There are only four types of reactions in this part of the pathway  

Interconversion of a keto sugar (ribulose 5-phosphate or fructose-6-phosphate) and an aldo sugar (ribose 5-phosphate or glucose-6-phosphate) by an isomerase. 

Inversion of the optical configuration of an optically active carbon atom, as in a conversion of ribulose 5-phosphate to xylulose 5-phosphate by an epimerase. 

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. 

Transfer of a two-carbon unit from a 2-keto sugar to the carbonyl carbon (Ci) of an aldose by a transketolase, which requires thiamine pyrophosphate and magnesium as cofactors. A covalent enzyme-substrate intermediate is formed similar to the one that occurs during the pyruvate dehydrogenase reaction (Chapter 13). 

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The pathway has an oxidative phase, which is irreversible and generates NADPH and a nonoxidative phase, which is reversible and provides ribose precursors for nucleotide synthesis. The complete pathway is present only in those tissues having a requirement for NADPH for reductive syntheses, eg, lipogenesis or steroidogenesis, whereas the nonoxidative phase is present in all cells requiring ribose. 

B. The PPP operates in two phases an oxidative phase and a nonoxidative phase. 

The nonoxidative phase consists of a series of sugar-phosphate interconversions that result in the conversion of ribulose 5-phosphate to ribose 5-phosphate (Figure 6-3). 

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.

NADPH formed in the oxidative phase is used to reduce glutathione, GSSG (see Box 14-3) and to support reductive biosynthesis. The other product of the oxidative phase is ribose 5-phosphate, which serves as precursor for nucleotides, coenzymes, and nucleic acids. In cells that are not using ribose 5-phosphate for biosynthesis, the nonoxidative phase recycles six molecules of the pentose into five molecules of the hexose glucose 6-phosphate, allowing continued production of NADPH and converting glucose 6-phosphate (in six cycles) to C02. 

The Nonoxidative Phase Recycles Pentose Phosphates to Glucose 6-Phosphate... 

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 ... 

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. 

In the nonoxidative phase, the pathway catalyzes the interconversion of three-, four-, five-, six-, and seven-carbon sugars in a series of nonoxidative reactions that can result in the synthesis of five-carbon sugars for nucleotide biosynthesis or the conversion of excess five-carbon sugars into intermediates of the glycolytic pathway. All these reactions take place in the cytosol. These interconversions rely on the same reactions that lead to the regeneration of ribulose 1,5-bisphosphate in the Calvin cycle. 

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.

Phosphogluconate + NADP+ ribulose 5-phosphate + CO2 + NADPH Nonoxidative Phase 6-Phosphogluconate dehydrogenase... 

In this phase, ribulose 3-phosphate is converted to glucose-6-phosphate. Stoichiometrically, this requires the rearrangement of six molecules of ketopentose phosphate to five molecules of aldohexose phosphate (Figure 15-20). It has been claimed that the pathway shown in Figure 15-20 occurs primarily in fat tissue and that a modified pathway involving arabinose 5-phosphate and octulose 8-phosphate occurs in liver cells. The overall scheme of the nonoxidative phase should be considered tentative. 

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 nonoxidative phase involves the isomerization and condensation of a number of different sugar molecules. Three intermediates in this process that are useful in other pathways are ribose-5-phosphate, fructose-6-phosphate, and glyceraldehyde-3-phosphate. 

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... 

Nonoxidative Phase (note how products of each reaction are shuffled - the pathway does not lead to a single end product)... 

The Nonoxidative Phase Alternative Fates of Pentose Phosphates... 

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