Biosynthesis sugar phosphate

Chapters 17 through 21 deal with carbohydrate-enzyme systems. Hehre presents some new ideas on the action of amylases. Kabat presents some new immunochemical studies on the carbohydrate moiety of certain water-soluble blood-group substances and their precursor antigens. Hassid reviews the role of sugar phosphates in the biosynthesis of complex saccharides. Pazur and co-workers present information obtained by isotopic techniques on the nature of enzyme-substrate complexes in the hydrolysis of polysaccharides. Gabriel presents a common mechanism for the production of 6-deoxyhexoses. An intermediate nucleoside-5 -(6-deoxyhexose-4-ulose pyrophosphate) is formed in each of the syntheses. 

The Role of Sugar Phosphate in the Biosynthesis of Complex Saccharides... 

The )8-(1 2)- and a-(1 5)-linked arabinose residues are incorporated into the polymer from the activated polyprenyl sugar phosphate 10, which is in turn synthesized from glucose via 5-phosphoribose pyrophosphate (pRpp) [46-48]. Elongation of the polymer chain is believed to involve a family of arabinosyltransferases (AraT s) that recognize both 10 and arabinofuranoside-based acceptors of differing structures (Fig. 5) [18,19,49,50]. In AG biosynthesis, the entire polysaccharide appears to be assembled as a polyprenol diphosphate intermediate, which is transferred to peptidoglycan prior to the addition of the mycolate esters [18]. In LAM biogenesis, the arabinan portion is believed to be synthesized as a polyprenol phosphate that is transferred to lipomannan [51]. 

In addition to providing reducing power (NADPH), the pentose phosphate pathway provides sugar phosphates that are required for biosynthesis. For instance, ribose-5-phosphate is used for the s5mthesis of nucleotides such as ATP. The four-carbon sugar phosphate, erythrose-4-phosphate, produced in the third stage of the pentose phosphate pathway is a precursor of the amino acids phenylalanine, tyrosine, and tryptophan. 

The pentose phosphate pathway is an important pathway for generating NADPH (for biosynthetic reactions) and pentose sugars (for nucleotide biosynthesis). It operates exclusively in the cytosol. Be aware that in contrast to pathways, such as glycolysis (with a linear sequence of reactions) or the citric acid cycle (with a circular sequence of reactions), the pentose phosphate pathway has several possible "branches" that can be taken to allow it to supply the cell with different products as needed. The primary products of the pathway include NADPH (from the oxidative reactions), pentoses (used in nucleotide synthesis), and miscellaneous other sugar phosphates. 

Glycolysis has functions in addition to ATP production. For example, in liver and adipose tissue, this pathway generates pyruvate as a precursor for fatty acid biosynthesis Glycolysis also provides precursors for the synthesis of compounds such as amino acids and 5-carbon sugar phosphates. 

In pyrimidine biosynthesis, the base is first formed and then attached to the sugar phosphate. Pyrimidinesare degraded to 13-alanine. 

It should be noted that isoprenoid biosynthesis requires acetyl-CoA, ATP, and NADPH. The physiological source of these compounds is presumably sugar phosphate metabolism, via glycolysis and the pentose phosphate pathway. We show sucrose as the starting material in Fig. 1, since it is the principal transport sugar in plants. Free acetate is not an important metabolite in plants acetyl-CoA is normally derived from pyruvate formed in glycolysis. Biosynthesis of terpenes implies that acetyl-CoA is diverted from the Krebs cycle and that the energy available from the Krebs cycle and oxidative phos-... 

Phosphoribosyl 1-pyrophosphate. S-phos-phoribosa 1-diphosphate, PftPP an energy-rich sugar phosphate, M, 390.1, formed by transfer of a pyro-phosphoryl residue from ATP to ribose 5-phosphate. PRPP is concerned in various biosynthetic reactions, e.g. biosynthesis of purines, pyrimidines and histidine. 

Activation by fructose-1, 6-diphosphate offers an attractive possibility for regulation in view of the long-established relationship between glucose utilization and lipogenesis in a number of tissues [87,98,100, 101,244]. The levels of fructose-1, 6-diphosphate are known [245] to vary in the same direction as the rate of fatty acid biosynthesis for example, fructose-1, 6-diphosphate concentration in liver is lower in the fasted and diabetic state, conditions in which fatty acid synthesis is depressed. Further work will be necessary to determine whether activation of the synthetase by sugar phosphates has physiological significance. 

The participation of polyprenol sugar phosphates as intermediates in the biosynthesis of several types of complex carbohydrate has been clearly established in bacteria (for a review see ref. 11). Tanner in 1969< > presented the first evidence of the possible participation of lipid carriers in yeast. This was confirmed by us and the carrier was found to be a phosphodiester of mannose and an isoprenoid alcohol.Finally, Jung and Tanner purified a lipid which was able to accept mannose from GDP-mannose when added exogenously to a particulate preparation. This lipid was characterized as a dolichol phosphate. 

Both L- and D-ribose occur in this complex mixture, but are not particularly abundant. Since all carbohydrates have somewhat similar chemical properties, it is difficult to envision simple mechanisms that could lead to the enrichment of ribose from this mixture, or how the relative yield of ribose required for the formation of RNA could be enhanced. However, the recognition that the biosynthesis of sugars leads not to the formation of free carbohydrates but of sugar phosphates, lead Albert Eschenmoser and his associates to show that under slightly basic conditions the condensation of glycoaldehyde-2-phosphate in the presence of formaldehyde considerable selectivity exist in the synthesis of ribose-2,4-diphosphate 54). This reaction has also been shown to take place under neutral conditions and low concentrations in the presence of minerals (55), and is particularly attractive given the properties of pyranosyl-RNA (p-RNA), a 2 ,4 -linked nucleic acid analogue whose backbone includes the six-member pyranose form of ribose-2,4-diphosphate 56). 

Because sugars are involved in most of the mechanisms established for the synthesis of these heterocycles, the development of carbohydrate chemistry has been most helpful in these researches—especially for the preparation of specifically labeled molecules. Conversely, the contribution of these efforts to carbohydrate chemistry and biochemistry has shown the involvement in biosynthesis of 1 -deoxy-D-f/rreo-pentulose—scarcely before recognized and considered a rare sugar—and of fully functionalized pentuloses of still unknown configuration (or their phosphates). Finally, evidence has been found in prokaryotes for a most extraordinary transformation of 5-amino-l-(P-D-ribofuranosyl)imidazole 5 -phos-phate into a pyrimidine. Surely, this transformation should be explained in terms... 

Some sugar residues in bacterial polysaccharides are etherified with lactic acid. The biosynthesis of these involves C)-alkylation, by reaction with enol-pyruvate phosphate, to an enol ether (34) of pyruvic acid, followed by reduction to the (R) or (5) form of the lactic acid ether (35). The enol ether may also react in a different manner, giving a cyclic acetal (36) of pyruvic acid. 

The biosynthesis of Kdo and neuraminic acid is known to involve enol-pyruvate phosphate and D-arabinose or 2-acetamido-2-deoxy-D-mannose, respectively. Nothing is known about the biosynthesis of all the other glycu-losonic acids. One interesting problem is, for example, whether the two 5,7-diamino-3,5,7,9-tetradeoxynonulosonic acids are synthesized analogously to neuraminic acid, from a three- and a six-carbon fragment, by modification of neuraminic acid on the sugar nucleotide level, or by a third, less obvious route. 

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