FIGURE 18.14 These of reduced ‘slesinedimeleotide phowphate (NADPH). 18.4 Glucose Is Sometimes Diverted through the Pentose Phosphate Pathway ‘The pentose phosphate pathway is an alternative to glycolysis and differs from i in several important ways, In glycolysis, one of our most important concerns was the production of ATP. In the pentose phosphate pathway, the production of ATP is not the crux of the matter, As the name of the pathway indicates, fivecearbon sugars, including ribose, are produced from glucose. Ribose and its derivative deoxyribose play an important role in the structure of nucleic acids, “Another important facet of the pentose phosphate pathway is the production of nicotinamide adenine dinucleotide phosphate (NADPH), a compouine that differs from nicotinamide adenine dinucleotide (NADH) by having one extra phosphate group esterified to the ribose ring of the adenine nucleotide portion, of the molecule (Figure 18.14). A more important difference is the way these ‘wo coenzymes function, NADH is produced in the oxidative reactions that give tse to ATP. NADPH isa reducing agent in biosynthesis, which, by itsvery nature, isa reductive process. For example, in Chapter 21, we shall see the important role that NADPH plays in the biosynthesis of lipids. ‘The pentose phosphate pathway begins with a series of oxidation reactions ‘that produce NADPH and fivecarbon sugars, The remainder of the path- way involves nonoxidative reshuulling of the carbon skeletons of the stigars inwolved. The products of these nonoxidative reactions include substances stich, as fructosesphosphate and glyceraldehyde-S-phosphate, which play a role in slycolysis, Some of these reshulling reactions will reappear when we look at the production of sugars in photosynthesis, What are the oxidative reactions of the pentose phosphate pathway? In the first reaction of the pathway, glucose6-phosphate i oxidized wo 6 phosphogluconate (Figure 18.15, of). The enzyme that catalyzes this reaction is glucose-6-phosphate dehydrogenase. Note that NADPH is produced by the reaction. “The next reaction is an oxidative decarboxylation, and NADPH is produced. ‘once again. The &phosphogluconate molecule loses its carboxyl group, which, is released as carbon dioxide, and the fivecarbon ketosugar (ketose) ribulose- Sxphosphate is the other product. The enzyme that catalyzes this reaction is Sphosphogluconate dehydrogenase. In the process, the G3 hydroxyl group of the Gphosphoghiconate is oxidized to form a keto acid, which is unstable and, readily decarboxylates to form ribulose-5-phosphate, What are the nonoxidative reactions of the pentose phosphate pathway, and why are they important? In the remaining steps of the pentose phosphate pathway, several reactions involve transfer of tor and threecarbon units To keep track of the carbon Iackbone of the sugars and their aldehyde and ketone fictional groups, we ‘hall write the formulas in the open-chain form. ‘There are two different reactions in which ribuloseS-phosphate isomer izes. In one of these reactions, catalyzed by phasphopentose epimerase, there is an inversion of configuration around carbon atom 3, producing xylulose- phosphate, which is also a ketose (Figure 18.15, éoitom)."The other isomeriza- tion reaction, catalyzed by phosphepentose isomerase, produces a sugar with an aldehyde group (an aldose) rather than a Ketone. In this second reaction, ribulose-5-phosphate isomerizes to ribose5-phosphate (Figure 18.15, fetton). Rihose-S-phosphate is a necessary building block for the synthesis of nucleic acids and cownzymes stch as NADH,184 Glucose ls Sometimes Diverted through the Pentose Phosphate Pathway 637 so ON + + Napeit Biochemistry Z Now ACTIVE FIGURE 18.15 the pentose phosphate pathway. The numerals inthe indict he ext Signet wr thomson ca aren lyin gpd nen Sn a 9g en538 Chapter 18 Storage Mechanisms and Control in Carbohydrate Metabolism The group-transfer reactions that link the pentose phosphate pathway with glycolysis require the two five-carbon sugars produced by the isomeriza tion of ribulose-5-phosphate. Two molecules of xylulose-5-phosphate and one molecule of ribose-5-phosphate rearrange to give two molecules of fructose-6- phosphate and one molecule of glyceraldehyde-3-phosphate. In other words, three molecules of pentose (with five carbon atoms each) give two molecules of hexose (with six carbon atoms each) and one molecule of a triose (with three carbon atoms). The total number of carbon atoms (15) does not change, but there is considerable rearrangement as a result of group transfer. Two enzymes, transketolase and. transaldolase, are responsible for the reshuf fling of the carbon atoms of sugars such as ribose-5-phosphate and xylulose-5- phosphate in the remainder of the pathway, which consists of three reactions. Transketolase transfers a two-carbon unit. Transaldolase transfers a thre carbon unit, Transketolase catalyzes the first and third reactions in the rear rangement process, and transaldolase catalyzes the second reaction, The results of these transfers are summarized in Table 18.2. In the first of these reactions, a two-carbon unit from xylulose-5-phosphate (five carbons) is trans ferred to ribose-5-phosphate (five carbons) to give sedoheptulose-7-phosphate (seven carbons) and glyceraldehyde-3-phosphate (three carbons), as shown in Figure 18.15, bottom, red numeral 1. In the reaction catalyzed by transaldolase, a three-carbon unit is trans ferred from the seven-carbon sedoheptulose-7-phosphate to the three-carbon glyceraldehyde-3-phosphate (Figure 18.15, red numeral 2). The products of the reaction are fructose-6-phosphate (six carbons) and erythrose-4-phos phate (four carbons). In the final reaction of this type in the pathway, xylulose-5-phosphate reacts with erythrose-4-phosphate. This reaction is catalyzed by transketolase. The products of the reaction are fructose-6-phosphate and glyceraldehyde phosphate (Figure 18.15, red numeral 3). In the pentose phosphate pathway, glucose-6-phosphate can be converted to fructose-6-phosphate and glyceraldehyde-3-phosphate by a means other than the glycolytic pathway. For this reason, the pentose phosphate pathway is also called the hexose monophosphate shunt, and this name is used in some texts. A major feature of the pentose phosphate pathway is the production of ribose- Sphosphate and NADPH. The control mechanisms of the pentose phosphate pathway can respond to the varying needs of organisms for either or both of these compounds.How is the pentose phosphate pathway controlled? As we ha e seen, the reactions catalyzed by wansketolase and transaldolase are reversible, which allows the pentose phosphate pathway to respond to the needs Transketolase Tworcarbon shift G+ G, s ‘Transaldolase /Three-casbon shift CG, Cy = ‘Transetolase ‘Twocarhon shift G+ Gy 5 Net reaction, Cy = 184 Glucose Is Sometimes Diverted through the Pentose Phosphate Pathway ‘of an organism. The starting material, glucose-6-phosphate, undergoes different reactions depending on whether there isa greater need for ribose-5-phesphate ‘or for NADPH. The operation of the oxidative portion of the pathway depends strongly on the organism's requirement for NADPH. The need for ribose-5- phosphate can be met in other ways, since ribose-5-phosphate can be obtained from glycolytic intermediates without the oxidative reactions of the pentose phosphate pathway (Figure 18.16). Ifthe organism needs more NADPH than riboseS-phosphate, the reaction, series goes through the complete pathway usted. The oxidative reae- tions at the beginning of the pathway are needed to produce NADPH. The net reaction for the oxidative portion of the pathway is 6 Glucose-6-phosphate + 12NADP* + 6H,0 > 6 Ribose T2NADPH + 12H" esphate + 6CC ‘The following Biochemical Connections box discusses a clinical manifestation ‘of an enzyme malfunction in the pentose phosphate pathway. Ifthe organism has a greater need for ribose-5-phosphate than for NADPH, fructose-6;phosphate and glyceraldehyde3-phosphate can give rise to ribose-5 phosphate by the successive operation of the tansketolase and ansaldolase reactions, bypassing the oxidative portion of the pentose phosphate pathway (follow the red shaded path down to glyceraldehydeSephosphate and then go Lup to ribose-5-phosphate) (Figure 18.16). The reactions catalyzed by tansketo- lase and transaldolase are reversible,and this fact plays: ‘organism's ability to adjust its metabolism to changes now look at the mode of action of these two enzyme n important role in the n conditions. We shall