Pentose-5-phosphate

This is not the place to expose in detail the problems and the solutions already obtained in studying biochemical reaction networks. However, because of the importance of this problem and the great recent interest in understanding metabolic networks, we hope to throw a little light on this area. Figure 10.3-23 shows a model for the metabolic pathways involved in the central carbon metabolism of Escherichia coli through glycolysis and the pentose phosphate pathway [22]. 

Figure 10.3-23. Metabolic model of glycolysis and tbe pentose phosphate pathway in E. coli. Squares Indicate enzyme activities circles indicate regulatory effects,...

Most of the enzymes mediating the reactions of the Calvin cycle also participate in either glycolysis (Chapter 19) or the pentose phosphate pathway (Chapter 23). The aim of the Calvin scheme is to account for hexose formation from 3-phosphoglycerate. In the course of this metabolic sequence, the NADPH and ATP produced in the light reactions are consumed, as indicated earlier in Equation (22.3). 

Gluconeogenesis, Glycogen Metabolism, and the Pentose Phosphate Pathway... 

Vnother pathway of glucose catabolism, the pentose phosphate pathway, is the primary source of N/ E)PH, the reduced coenzyme essential to most reductive biosynthetic processes. For example, N/VDPH is crucial to the biosynthesis of... 

Cells require a constant supply of N/ X)PH for reductive reactions vital to biosynthetic purposes. Much of this requirement is met by a glucose-based metabolic sequence variously called the pentose phosphate pathway, the hexose monophosphate shunt, or the phosphogluconate pathway. In addition to providing N/VDPH for biosynthetic processes, this pathway produces ribos 5-phosphate, which is essential for nucleic acid synthesis. Several metabolites of the pentose phosphate pathway can also be shuttled into glycolysis. 

FIGURE 23.26 The pentose phosphate pathway. The numerals in the blue circles indicate the steps discussed in the text. 

FIGURE 23.27 The glucose-6-phosphate dehydrogenase reaction is the committed step in the pentose phosphate pathway. 

This enzyme interconverts ribulose-5-P and ribose-5-P via an enediol intermediate (Figure 23.30). The reaction (and mechanism) is quite similar to the phosphoglucoisomerase reaction of glycolysis, which interconverts glucose-6-P and fructose-6-P. The ribose-5-P produced in this reaction is utilized in the biosynthesis of coenzymes (including N/ DH, N/ DPH, F/ D, and Big), nucleotides, and nucleic acids (DNA and RNA). The net reaction for the first four steps of the pentose phosphate pathway is... 

To this point, the pathway has generated a pool of pentose phosphates. The AG° for each of the last two reactions is small, and the three pentose-5-phosphates coexist at equilibrium. The pathway has also produced two molecules of N/ DPH for each glucose-6-P converted to pentose-5-phosphate. The next three steps rearrange the five-carbon skeletons of the pentoses to produce three-, four-, six-, and seven-carbon units, which can be used for various metabolic purposes. Why should the cell do this Very often, the cellular need for... 

Even when the latter choice has been made, however, the cell must still be cognizant of the relative needs for ribose-5-phosphate and N/VDPH (as well as ATP). Depending on these relative needs, the reactions of glycolysis and the pentose phosphate pathway can be combined in novel ways to emphasize the synthesis of needed metabolites. There are four principal possibilities. 

BOTH RIBOSE-5-P AND NADPH ARE NEEDED BY THE CELL In this case, the first four reactions of the pentose phosphate pathway predominate (Figure 23.37). N/VDPH is produced by the oxidative reactions of the pathway, and ribose-5-P is the principal product of carbon metabolism. As stated earlier, the net reaction for these processes is... 

MORE RIBOSE-5-P THAN NADPH IS NEEDED BY THE CELL Synthesis of ribose-5-P can be accomplished without production of N/VDPH if the oxidative steps of the pentose phosphate pathway are bypassed. The key to this route is the extrac-... 

FIGURE 23.37 Wlien biosynthetic demands dictate, the first four reactions of the pentose phosphate pathway predominate and the principal products are ribose-5-P and NADPH. 

---