Reductive pentose phosphate pathway

Glcose-6-phosphate is a key metabolite in the sugar metabolism and located at a fork to the glycolysis and pentose phosphate pathway. Reduction of the carbon flux... 

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. 

Generally, NAD-linked dehydrogenases catalyze ox-idoreduction reactions in the oxidative pathways of metabolism, particularly in glycolysis, in the citric acid cycle, and in the respiratory chain of mitochondria. NADP-linked dehydrogenases are found characteristically in reductive syntheses, as in the extramitochon-drial pathway of fatty acid synthesis and steroid synthesis—and also in the pentose phosphate pathway. 

The importance of having adequate supplies of NADPH for the regeneration of these various enzymes cannot be over emphasized. In normal situations this cofactor can be adequately provided by the reductive pentose phosphate pathway. Monitoring the activity of the pentose phosphate pathway has been proposed as a unique way to study the metabolic response to oxidative stress, since the glutathione peroxidase activity is coupled via glutathione reductase to the enzyme glucose-6-phosphate dehydrogenase (Ben Yoseph et ah, 1994). 

Figure 11.4 Condensation, dehydration and reduction reactions in fatty add synthesis. These reactions constitute the major components of the pathway of fatty acid synthesis and are all catalysed by fatty acid synthase. The reduction reactions, indicated by addition of 2H in the diagram, involve the conversion of NADPH to NADP . (The re-conversion of NADP back to NADPH occurs in the pentose phosphate pathway.) The condensation reaction results in an increase in size of acyl-ACP by two carbon units in each step. The two carbons for each extension are each provided by malonyl-CoA. ACP - acyl carrier protein.

The reduced coenzyme NADPH is required for the reduction reactions shown in Figure 11.5. It is also required for elongation and desaturation of fatty acids. The major source of NADPH for these reactions is the pentose phosphate pathway, which is described in detail in Chapter 6. 

The final reactions to be considered in the metabolism of ethanol in the liver are those involved in reoxidation of cytosolic NADH and in the reduction of NADP. The latter is achieved by the pentose phosphate pathway which has a high capacity in the liver (Chapter 6). The cytosolic NADH is reoxidised mainly by the mitochondrial electron transfer system, which means that substrate shuttles must be used to transport the hydrogen atoms into the mitochondria. The malate/aspartate is the main shuttle involved. Under some conditions, the rate of transfer of hydrogen atoms by the shuttle is less than the rate of NADH generation so that the redox state in the cytosolic compartment of the liver becomes highly reduced and the concentration of NAD severely decreased. This limits the rate of ethanol oxidation by alcohol dehydrogenase. 

The deoxyribonucleotides, except for deoxythymidine nucleotide, are formed from the ribonucleotides by the action of an enzyme complex, which comprises two enzymes, ribonucleoside diphosphate reductase and thioredoxin reductase (Figure 20.11). The removal of a hydroxyl group in the ribose part of the molecule is a reduction reaction, which requires NADPH. This is generated in the pentose phosphate pathway. (Note, this pathway is important in proliferating cells not only for generation... 

In the second phase, transaldolase (with TPP as cofactor) and transketolase catalyze the interconversion of three-, four-, five-, six-, and seven-carbon sugars, with the reversible conversion of six pentose phosphates to five hexose phosphates. In the carbon-assimilating reactions of photosynthesis, the same enzymes catalyze the reverse process, called the reductive pentose phosphate pathway conversion of five hexose phosphates to six pentose phosphates. 

Glucose 6-phosphate dehydrogenase, the first enzyme in the oxidative pentose phosphate pathway, is also regulated by this light-driven reduction mechanism, but in the opposite sense. During the day, when photosynthesis produces plenty of NADPH, this enzyme is not needed for NADPH production. Reduction of a critical disulfide bond by electrons from ferredoxin inactivates the enzyme. 

Calvin cycle 752 plastids 752 chloroplast 752 amyloplast 752 carbon-fixation reaction 753 ribulose 1,5-bisphosphate 753 3-phosphoglycerate 753 pentose phosphate pathway 753 reductive pentose phosphate pathway 753 C3 plants 754 ribulose 1,5-bisphosphate carboxylase/oxygenase (rubisco) 754 rubisco activase 757... 

Comparison of the Reductive and Oxidative Pentose Phosphate Pathways The reductive pentose phosphate pathway generates a number of intermediates identical to those of the oxidative pentose phosphate pathway (Chapter 14). What role does each pathway play in cells where it is active ... 

Penicillin 20 Penicillin acylase 620 Penicillopepsin 621 Pentose phosphate pathway 700 reductive 517 Pentoses 162... 

A quantitatively much more important pathway of C02 fixation is the reductive pentose phosphate pathway (ribulose bisphosphate cycle or Calvin-Benson cycle Fig. 17-14). This sequence of reactions, which takes place in the chloroplasts of green plants and also in many chemiautotrophic bacteria, is essentially a way of reversing the oxidative pentose phosphate pathway (Fig. 17-8). The latter accomplishes the complete oxidation of glucose or of glucose 1-phosphate by NADP+ (Eq. 17-48) ... 

The reactions enclosed within the shaded box of Fig. 17-14 do not give the whole story about the coupling mechanism. A phospho group was transferred from ATP in step a and to complete the hydrolysis it must be removed in some future step. This is indicated in a general way in Fig. 17-14 by the reaction steps d, e, and/. Step/represents the action of specific phosphatases that remove phospho groups from the seven-carbon sedoheptulose bisphosphate and from fructose bisphosphate. In either case the resulting ketose monophosphate reacts with an aldose (via transketolase, step g) to regenerate ribulose 5-phosphate, the C02 acceptor. The overall reductive pentose phosphate cycle (Fig. 17-14B) is easy to understand as a reversal of the oxidative pentose phosphate pathway in which the oxidative decarboxylation system of Eq. 17-12 is... 

Figure 17-14 (A) The reductive carboxylation system used in reductive pentose phosphate pathway (Calvin-Benson cycle). The essential reactions of this system are enclosed within the dashed box. Typical subsequent reactions follow. The phosphatase action completes the phosphorylation-dephosphorylation cycle. (B) The reductive pentose phosphate cycle arranged to show the combining of three C02 molecules to form one molecule of triose phosphate. Abbreviations are RCS, reductive carboxylation system (from above) A, aldolase, Pase, specific phosphatase and TK, transketolase.

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