NADPH from pentose phosphate pathway

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). 

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 ... 

The pentose phosphate pathway is an alternative route for the metabolism of glucose. It does not generate ATP but has two major functions (1) The formation of NADPH for synthesis of fatty acids and steroids and (2) the synthesis of ribose for nucleotide and nucleic acid formation. Glucose, fructose, and galactose are the main hexoses absorbed from the gastrointestinal tract, derived principally from dietary starch, sucrose, and lactose, respectively. Fructose and galactose are converted to glucose, mainly in the liver. 

The NADPH is produced from glucose 6-phosphate in the first three reactions in the pentose phosphate pathway (see below). Hence the pentose phosphate pathway is essential in the erythrocyte and glycolysis provides the substrate glucose 6-phosphate. Individuals with a reduced amount of glucose 6-phosphate dehydrogenase can suffer from oxidative damage to their cells and hence haemolysis. 

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... 

The pentose phosphate pathway (PPP, also known as the hexose monophosphate pathway) is an oxidative metabolic pathway located in the cytoplasm, which, like glycolysis, starts from glucose 6-phosphate. It supplies two important precursors for anabolic pathways NADPH+H+, which is required for the biosynthesis of fatty acids and isopren-oids, for example (see p. 168), and ribose 5-phosphate, a precursor in nucleotide biosynthesis (see p. 188). 

The first step is carboxylation of acetyl CoA to malonyl CoA. This reaction is catalyzed by acetyl-CoA carboxylase [5], which is the key enzyme in fatty acid biosynthesis. Synthesis into fatty acids is carried out by fatty acid synthase [6]. This multifunctional enzyme (see p. 168) starts with one molecule of ace-tyl-CoA and elongates it by adding malonyl groups in seven reaction cycles until palmi-tate is reached. One CO2 molecule is released in each reaction cycle. The fatty acid therefore grows by two carbon units each time. NADPH+H is used as the reducing agent and is derived either from the pentose phosphate pathway (see p. 152) or from isocitrate dehydrogenase and malic enzyme reactions. 

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. 

VLDLs to fat and muscle tissue. The NADPH necessary for lipid synthesis is obtained by oxidation of glucose in the pentose phosphate pathway. Excess amino acids are converted to pyruvate and acetyl-CoA, which are also used for lipid synthesis. Dietary fats move via the lymphatic system, as chylomicrons, from the intestine to muscle and fat tissues. 

How is the cytoplasmic [NADPH]/[NADP+] ratio maintained at a value higher than that of [NADH]/ [NAD+] Part of the answer is from operation of the pentose phosphate pathway (Section E,3). The reactions of Eq. 17-12, if they attained equilibrium, would give a ratio of cytosolic [NADPH]/[NADP+] > 2000 at 0.05 atm C02. Compare this with the ratio 1 /634 for [NADH/[NAD+] deduced from the observation on the reactions of Eq. 17-42. 

Many kinds of organisms and some mammalian organs, notably liver, possess an alternative pathway for the oxidation of hexoses which results in a pentose phosphate and carbon dioxide. This pentose can be used as a precursor of the ribose found in nucleic acids or other sugars containing from three to seven carbon atoms which are needed in smaller amounts. The first and third reactions in the pentose phosphate pathway generate NADPH which is a major source of reducing power in many cells. 

Answer The reductive pentose phosphate pathway regenerates ribulose 1,5-bisphosphate from triose phosphates produced during photosynthesis, in a series of reactions involving sugars of three, four, five, six, and seven carbons and the enzymes transaldolase and transketo-lase. The oxidative pentose phosphate pathway plays a different metabolic role it provides NADPH for reductive biosynthesis and pentose phosphates for nucleotide synthesis. 

Figure 2.4. The provision of acetyl-CoA and NADPH for lipogenesis. PPP, pentose phosphate pathway T, tricarboxylate transporter K, a-ketoglutarate transporter. In ruminants, pyruvate dehydrogenase, ATP-citrate lyase and malic enzyme activities are low and perhaps non-functional. (From Murray et al., 1988. Harper s Biochemistry, 21st edn, p. 207, Appleton and Lange, Norwalk, CT reproduced with permission of The McGraw-Hill Companies).

Mode 2. The needs for NADPH and ribose 5-phosphate are balanced. The predominant reaction under these conditions is the formation of two molecules of NADPH and one molecule of ribose 5-phosphate from one molecule of glucose 6-phosphate in the oxidative phase of the pentose phosphate pathway. The stoichiometry of mode 2 is... 

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