The Pentose Phosphate Pathways

The plant can also use the pentose phosphate pathway to break down glucose, but the main purpose of this pathway is the generation of reducing power in the form of NADPH (nicotinamide adenine dinucleotide 

Ribulose-5-phosphate (3.13) can be converted to ribose-5-phosphate (3.14) and xylulose 5-phosphate (3.15), by the enzymes ribose-5-phosphate isomerase and ribulose 5-phosphate 3-epimerase, respectively. The two pentose-phosphate molecules, 3.14 and 3.15, are converted to a C3 and a C7 sugar-phosphate, glyceraldehyde 3-phosphate (3.4) and sedoheptulose-7-phosphate (3.16), respectively, via the action of atransketolase. 

Transketolases are characterized by their ability to transfer a two-carbon unit from a ketose to an aldehyde. The C3 and C7 sugar-phosphates can subsequently be converted to a C4 and a C s sugar-phosphate, erythrose 4-phosphate (3.17) and fructose 6-phosphate (3.2), respectively. This reaction is catalyzed by a transaldolase, which transfers a three-carbon glyceraldehyde unit from an aldose to a ketose. Erythrose-4-phosphate (3.17) can be used in the shikimate pathway (see Section 6). A second transketolase reaction can generate a second fructose-6-phosphate (3.2) and glyceraldehyde-3-phosphate (3.4) residue from erythrose-4-phosphate (3.17) and xylulose-5-phosphate (3.15). Hexose-phosphate isomerase converts the 

So in summary, three glucose-6-phosphate (3.1) molecules (3 x C6) are oxidized to three ribulose-5-phosphate (3.13) residues (3 x C5) and three molecules of C02 (3 x Ci) under generation of six molecules of NADPH. The three ribulose-5-phosphate residues are then converted to one glyceraldehyde-3-phosphate (3.14) molecule (lx C3) and two fructose-6-phosphate (3.2) molecules (2 x C6). Fructose-6-phosphate can be converted to glucose-6-phosphate and reenter the oxidative part of the pentose phosphate pathway. Fructose-6-phosphate and glyceraldehydes can also serve as intermediates in glycolysis (Section 5.1), which offers the cell considerable flexibility in terms of its metabolic flux. 

This pathway is variously known as the pentose phosphate, hexose monophosphate or phosphogluconate pathway, cycle or shunt. Although the pentose phosphate pathway achieves oxidation of glucose, this is not its function, as indicated by the distribution of the pathway in different tissues. Only one of the carbons is released as CO2, the key products are NADPH and ribose 5-phosphate, both of which are important for nucleotide phosphate formation and hence for synthesis of nucleic acids (Chapter 20). The 

Process Activation Large binding system Binding sites Condensation Elongation and movement Termination Post-synthetic modifications 

Glycogen Formation of Glycogenin Binding of Condensation Movement of Not known, Hydration of 

Fatty acid Formation of Acyl carrier (i) acetyl site Condensation Transfer of Release of (i) Formation of 

Some mammalian cells have the ability to metabolize glucose 6-phosphate in a pathway that involves the production of C3, C4, C5, C6, and C7 sugars. This process also yields the reduced coenzyme, NADPH, which is oxidized in the biosynthesis of fatty acids and steroids (Chap. 13). Consequently, this metabolic pathway is of major importance in those cells involved in fatty acid and steroid production, such as the liver, lactating mammary gland, adrenal cortex, and adipose tissue. The pentose phosphate pathway, which does not require oxygen and which occurs in the cytoplasm of these cells, has two other names the phosphogluconate pathway (after the first product in the pathway) and the hexose monophosphate shunt (since the end products of the pathway can reenter glycolysis). 

TTie first step is the oxidation of glucose 6-phosphate at C-l, catalyzed by glucose-6-phosphate dehydrogenase, to produce a cyclic ester (also called a lactone)  

The 6-phosphogluconolactone is unstable, and the ester spontaneously hydrolyzes, although a specific enzyme (lactonase) also catalyzes this reaction (Step 2)  

The third step in the pathway yields a C5 sugar, D-ribulose 5-phosphate, and concomitantly reduces another molecule of NADP+. This is catalyzed by 6-phosphogluconate dehydrogenase  

D-Ribulose 5-phosphate then undergoes an isomerization by ribose-5-phosphate isomerase to o-ribose 5-phosphate (Step 4)  

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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]. 

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... 

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. 

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-... 

FIGURE 23.38 The oxidative steps of the pentose phosphate pathway can be bypassed if the primary need is for ribose-5-P. 

NADPH can be produced in the pentose phosphate pathway as well as by malic enzyme (Figure 25.1). Reducing equivalents (electrons) derived from glycolysis in the form of NADH can be transformed into NADPH by the combined action of malate dehydrogenase and malic enzyme ... 

How many of the 14 NADPH needed to form one palmitate (Eq. 25.1) can be made in this way The answer depends on the status of malate. Every citrate entering the cytosol produces one acetyl-CoA and one malate (Figure 25.1). Every malate oxidized by malic enzyme produces one NADPH, at the expense of a decarboxylation to pyruvate. Thus, when malate is oxidized, one NADPH is produced for every acetyl-CoA. Conversion of 8 acetyl-CoA units to one palmitate would then be accompanied by production of 8 NADPH. (The other 6 NADPH required [Eq. 25.1] would be provided by the pentose phosphate pathway.) On the other hand, for every malate returned to the mitochondria, one NADPH fewer is produced. 

The following compound is an intermediate in the pentose phosphate pathway, an alternative route for glucose metabolism. Identify the sugar it is derived from. 

Another step in the pentose phosphate pathway for degrading sugars (see Problem 29.38) is the conversion of ribose S-phosphate to glyceraldehyde 3-phosphate. What kind of organic process is occurring Propose a mechanism for the conversion. 

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. 

A number of lyases are known which, unlike the aldolases, require thiamine pyrophosphate as a cofactor in the transfer of acyl anion equivalents, but mechanistically act via enolate-type additions. The commercially available transketolase (EC 2.2.1.1) stems from the pentose phosphate pathway where it catalyzes the transfer of a hydroxyacetyl fragment from a ketose phosphate to an aldehyde phosphate. For synthetic purposes, the donor component can be replaced by hydroxypyruvate, which forms the reactive intermediate by an irreversible, spontaneous decarboxylation. 

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