Pentoses phosphorylation

A more complicated reaction sequence has been used by Ukita and Nagasawa (59) in their synthesis of 2-deoxy D-ribose 5-phosphate (2-deoxy D-erythro-pentose 5-(dihydrogen phosphate)), (29). They phosphorylated a mixture of the anomeric methyl deoxyribofuranosides (24)... 

The 3-deoxy pentose phosphates (44 and 45) can be further degraded to phosphorylated deoxy sugars (58) treatment of either of them with periodate will cleave the carbon-carbon bond between Ci and C2 to yield 2-deoxy-n- (46) and -L-gZycero-tetrose-4-phosphates (47). 

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. 

The 5 -phosphoryl group of a mononucleotide can es-terify a second —OH group, forming a phosphodi-ester. Most commonly, this second —OH group is the 3 -OH of the pentose of a second nucleotide. This forms a dinucleotide in which the pentose moieties are linked by a 3 —> 5 phosphodiester bond to form the backbone of RNA and DNA. 

The major biochemical features of neutrophils are summarized in Table 52-8. Prominent feamres are active aerobic glycolysis, active pentose phosphate pathway, moderately active oxidative phosphorylation (because mitochondria are relatively sparse), and a high content of lysosomal enzymes. Many of the enzymes listed in Table 52-4 are also of importance in the oxidative metabolism of neutrophils (see below). Table 52-9 summarizes the functions of some proteins that are relatively unique to neutrophils. 

D-Xylulose 5-phosphate (ii-threo-2-pentulose 5-phosphate, XP) stands as an important metabolite of the pentose phosphate pathway, which plays a key fimction in the cell and provides intermediates for biosynthetic pathways. The starting compound of the pathway is glucose 6-phosphate, but XP can also be formed by direct phosphorylation of D-xylulose with li-xylulokinase. Tritsch et al. [114] developed a radiometric test system for the measurement of D-xylulose kinase (XK) activity in crude cell extracts. Aliquots were spotted onto silica plates and developed in n-propyl alcohol-ethyl acetate-water (6 1 3 (v/v) to separate o-xylose/o-xylulose from XP. Silica was scraped off and determined by liquid scintillation. The conversion rate of [ " C]o-xylose into [ " C]o-xylulose 5-phosphate was calculated. Some of the works devoted to the separation of components necessary while analyzing enzyme activity are presented in Table 9.8. 

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]. 

Figure 20.9 The positions in the pathway for de novo pyrimidine nucleotide synthesis where GLUCOSE provides the ribose molecule and GLUTAMINE provides nitrogen atoms. Glucose forms ribose 5-phosphate, via the pentose phosphate pathway (see chapter 6), which enters the pathway, after phosphorylation, as 5-phospho-ribosyl 1-pyrophosphate. Glutamine provides the nitrogen atom to synthesise carbamoylphos-phate (with formation of glutamate), and also to form cytidine triphosphate (CTP) from uridine triphosphate (UTP), catalysed by the enzyme CTP synthetase. It is the amide nitrogen of glutamine that is the nitrogen atom that is provided in these reactions.

While NADH exclusively supplies oxidative phosphorylation, NADPH+H" —a very similar coenzyme—is the reducing agent for anabolic pathways. NADPH + is mainly formed in the pentose phosphate pathway (PPP, 1 see p. 152). 

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). 

Acyclovir (9.9) shows a unique specificity and lack of toxicity in HSV-1, HSV-2, and varicella (chickenpox, shingles) viral infections. A guanine derivative, acyclovir lacks the pentose of similar compounds and is phosphorylated at the alcoholic OH by the viral thymidylate kinase only. Consequently, it is not activated in uninfected cells additionally. 

The pentose phosphates formed in the transketolase reactions—ribose 5-phosphate and xylulose 5-phos-phate—are converted to ribulose 5-phosphate (steps (7) and (3)), which in the final step ( ) of the cycle is phosphorylated to ribulose 1,5-bisphosphate by ribulose 5-phosphate kinase (Fig. 20-13). This is the third very exergonic reaction of the pathway, as the phosphate anhydride bond in ATP is swapped for a phosphate ester in ribulose 1,5-bisphosphate. 

The pentose phosphates are converted to ribulose 5-phosphate, then phosphorylated to ribulose 1,5-bisphosphate to complete the Calvin cycle. 

Carbohydrate metabolism in a typical plant cell is more complex in several ways than that in a typical animal cell. The plant cell carries out the same processes that generate energy in animal cells (glycolysis, citric acid cycle, and oxidative phosphorylation) it can generate hexoses from three- or four-carbon compounds by glu-coneogenesis it can oxidize hexose phosphates to pentose phosphates with the generation of NADPH (the ox-... 

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.

Just as with the pentose phosphate cycle, an exact reversal of the glycolysis sequence (Eq. 17-53) is precluded on thermodynamic grounds. Even at very high values of the phosphorylation state ratio Rp, the reaction ... 

Photosynthesis. The formation of carbohydrates in green plants by the process of photosynthesis is described in ihc entry on Photosynthesis. The synthetic mechanism involves the addition of carbon dioxide to ribulose-1,5-diphosphate and the subsequent formation of two molecules of 3-phosphoglyccric acid which are reduced to glyceraldehyde-3-phosphate. The triose phosphates are utilized to again from ribulose-5-phosphates by enzymes of the pentose phosphate cycle Phosphorylation or ribulose-5-phosphate with ATP regenerates ribulose-1.5-diphosphate to accept another molecule of carbon dioxide. See also Phosphorylation (Photosynthetlc). 

The relationship of the pentose-phosphate pathway to glycolysis is shown in Figure 20-11. The steps involved in the pentose shunt are readily reversible, but there are several steps in glycolysis that are not. These are the phosphorylation steps (see Figure 20-9). Yet, there has to be a return route from pyruvate to glucose. This route is called gluconeogenesis and, in animals, takes place in... 

Metabolic Strategies 227 Glycolysis, Gluconeogenesis, and the Pentose Phosphate Pathway 242 The Tricarboxylic Acid Cycle 282 Electron Transport and Oxidative Phosphorylation 305 Photosynthesis 330 Structures and Metabolism of Oligosaccharides and Polysaccharides 356... 

Two NADPH Molecules Are Generated by the Pentose Phosphate Pathway Transaldolase and Transketolase Catalyze the Interconversion of Many Phosphorylated Sugars Production of Ribose-5-phosphate and Xylulose-5-phosphate... 

The pentose phosphate pathway serves a variety of functions (1) the production of NADPH for biosynthesis (2) the production of ribose, required mainly for nucleic acid synthesis, and (3) the interconversion of a variety of phosphorylated sugars. 

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