Pentose cycle pathway

The PRPP yield in the RBC was strikingly enhanced by addition of methylene blue or phenazine methosulfate. These artificial hydrogen acceptors stimulate the oxidative pentose cycle pathway and thereby increase the intracellular si )ply of Rib-5-P as the requisite substrate of PRPP synthetase. However, the stimulatory effect of the redox dyes failed to alter the stringent requirement for high Pi concentration. On the other hand, experiments performed with cell-free systems revealed that the activity of PRPP synthetase... 

Using the same reaction mixture as above but omitting NADP, so as to eliminate the oxidative pentose cycle pathway, we were able to reproduce essentially the characteristic response to Pi observed under anaerobic conditions in the intact RBC. As may be seen in Table 3, there was a definite shift of the Pi optimum towards physiological concentrations. The inhibitory effect of 15mM Pi seems to be attributable to interference of the Pi excess with the activity of the transaldolase-transketolase system mediating the non-oxidative pentose cycle path for Rib-5-P supply. 

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). 

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. 

Pathways are compartmentalized within the cell. Glycolysis, glycogenesis, glycogenolysis, the pentose phosphate pathway, and fipogenesis occur in the cytosol. The mitochondrion contains the enzymes of the citric acid cycle, P-oxidation of fatty acids, and of oxidative phosphorylation. The endoplasmic reticulum also contains the enzymes for many other processes, including protein synthesis, glycerofipid formation, and dmg metabolism. 

Figure 20-h Flow chart of pentose phosphate pathway and its connections with the pathway of glycolysis. The full pathway, as indicated, consists of three interconnected cycles in which glucose 6-phosphate is both substrate and end product. The reactions above the broken line are nonreversible, whereas all reactions under that line are freely reversible apart from that catalyzed by fructose-1,6-bisphosphatase. 

Erythrocytes Transport of O2 1 Glycolysis, pentose phosphate pathway. No mitochondria and therefore no p-oxidation or citric acid cycle. Glucose Lactate 1 (Hemoglobin) ... 

Nevertheless, using GC-based technologies, the quantification of several important intermediates of central metabolism, especially phosphorylated intermediates, is not very reliable, presumably because these compounds and their derivatives are not thermostable. For an analysis of these groups of metabolites, an LC-MS (liquid chromatography or HPLC coupled to MS) is more suitable, because it eliminates the need for volatility and thermostability and thereby eliminates the need for derivatization. Using a triple quadrupole MS, most of the intermediates in glycolysis, in the pentose phosphate pathway, and in the tricarboxylic acid cycle were measured in E. coli [214]. 

B. Luo, K. Groenke, R. Takors, C. Wandrey, and M. Oldiges, Simultaneous determination of multiple intracellular metabolites in glycolysis, pentose phosphate pathway and tricarboxylic acid cycle by liquid chromatography mass spectrometry. J. Chromatogr. A 1147, 153 164 (2007). 

ATP-proton motive force interconversion Electron transport Entner-Doudoroff Fermentation Glycolysis/gluconeogenesis Pentose phosphate pathway Pyruvate dehydrogenase Sugars TCA cycle Methanogenesis Polysaccharides Other... 

In addition to the common pathways, glycolysis and the TCA cycle, the liver is involved with the pentose phosphate pathway regulation of blood glucose concentration via glycogen turnover and gluconeogenesis interconversion of monosaccharides lipid syntheses lipoprotein formation ketogenesis bile acid and bile salt formation phase I and phase II reactions for detoxification of waste compounds haem synthesis and degradation synthesis of non-essential amino acids and urea synthesis. 

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... 

T) Pentose phosphate pathway Gluconeogenesis Glycolysis P-Oxidation (5) Fatty acid biosynthesis Tricarboxylic acid cycle (7) Urea cycle... 

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. 

In eukaryotes, the cytoplasm, representing slightly more than 50% of the cell volume, is the most important cellular compartment. It is the central reaction space of the cell. This is where many important pathways of the intermediary metabolism take place—e.g., glycolysis, the pentose phosphate pathway, the majority of gluconeogenesis, and fatty acid synthesis. Protein biosynthesis (translation see p. 250) also takes place in the cytoplasm. By contrast, fatty acid degradation, the tricarboxylic acid cycle, and oxidative phosphorylation are located in the mitochondria (see p. 210). 

Sabri Ml. 1984. In vitro effect of n-hexane and its metabolites on selected enzymes in glycolysis, pentose phosphate pathway and citric acid cycle. Brain Res 297 145-150. 

The reaction for each cycle indicates the high demand for ATP and also for reducing equivalents provided by NADPH, which are provided by the pentose phosphate pathway (see Chapter 6). 

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... 

All amino acids are derived from intermediates in glycolysis, the citric acid cycle, or the pentose phosphate pathway (Fig. 22-9). Nitrogen enters these pathways by way of glutamate and glutamine. Some pathways are simple, others are not. Ten of the amino acids are just one or several steps removed from the common metabolite from which they are derived. The biosynthetic pathways for others, such as the aromatic amino acids, are more complex. 

FIGURE 22-9 Overview of amino acid biosynthesis. The carbon skeleton precursors derive from three sources glycolysis (pink), the citric acid cycle (blue), and the pentose phosphate pathway (purple). 

Glucose 6-phosphate is the key intermediate in carbohydrate metabolism. It may be polymerized into glycogen, dephosphorylated to blood glucose, or converted to fatty acids via acetyl-CoA. It may undergo oxidation by glycolysis, the citric acid cycle, and respiratory chain to yield ATP, or enter the pentose phosphate pathway to yield pentoses and NADPH. 

Pentose phosphate pathway Summary of the path way Reduced coenzymes produced by the pathway PENTOSE PHOSPHATE PATHWAY (p. 143) Also called the hexose monophosphate shunt, or6-phosphogluconate pathway, the pentose phosphate pathway is found in all cells. It consists of two irreversible oxidative reac tions followed by a series of reversible sugar-phosphate interconversions. No ATP is directly consumed or produced in the cycle, and two NADPH are produced for each glu cose 6-phosphate entering the oxidative part of the pathway. 

Both catalyze chain cleavage and transfer reactions (Eqs. 17-14 and 17-15) that involve the same group of substrates. These enzymes use the two basic types of C-C bond cleavage, adjacent to a carbonyl group (a) and one carbon removed from a carbonyl group ((3). Both types are needed in the pentose phosphate pathways just as they are in the citric acid cycle. The enzymes of the pentose phosphate pathway are found in the cytoplasm of both animal and plant cells.n7c Mammalian cells appear to have an additional set that is active in the endoplasmic reticulum and plants have another set in the chloroplasts.117c... 

In these tissues the cycle may operate as indicated in Fig. 17-8A with the C3 product also being used in biosynthesis. Furthermore, any of the products from C4 to C7 may be withdrawn in any desired amounts without disrupting the smooth operation of the cycle. For example, the C4 intermediate erythrose 4-P is required in synthesis of aromatic amino acids by bacteria and plants (but not in animals). Ribose 5-P is needed for formation of several amino acids and of nucleic acids by all organisms. In some circumstances the formation of ribose 5-P may be the only essential function for the pentose phosphate pathway.120... 

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... 

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