Nucleoside diphosphate sugars biosynthesis

C. Nucleoside Diphosphate Sugars.—A polyprenol phosphate containing eleven isoprene units is involved in the biosynthesis of various bacterial cell-wall components.As mentioned in last year s Report, another isoprenoid phosphate, dolichol monophosphate (40), is an intermediate in sugar... 

Glycosyl—Enzyme Complex Intermediates in Biosynthesis of Complex Saccharides. The synthesis of nucleoside diphosphate sugars involves the transfer of a nucleotidyl group from a nucleoside triphosphate to a sugar 1-phosphate with the simultaneous release of pyrophosphate according to the following general reaction (11) ... 

The metabolic routes leading to polyglucan synthesis were elucidated after the discovery of nucleoside-diphosphate sugars by L. F. Leloir and co-workers in 1955. This finding led to the conclusion that biosynthesis and degradation of glycogen and starch occur by different pathways. 

The glucose-1-phosphate formed in reaction 2 is then converted to glucose-6-phosphate by phosphoglucomutase (reaction 4), an enzyme involved also in glycogen biosynthesis. Nucleoside diphosphate sugars such as UDP-glucose are widely used intermediates in polysaccharide biosynthesis. 

Nucleoside Diphosphate Sugars.—The biosynthesis of saccharides from sugar nucleotides has recently been reviewed. The incorporation of monosaccharides into bacterial cell walls involves the participation of... 

Sugar-l-P + XTP -> XDP-Sugar Scheme 14. Biosynthesis of Nucleoside Diphosphate Sugars. 

There is now a great deal of evidence that liposaccharide intermediates are involved in some biosyntheses of polysaccharides in animals and bacteria. This is an alternative to the UDP-sugar process (11.60) and utilises various nucleoside diphosphate sugars together with a polyprenol phosphate. The presence of a long hydrocarbon chain in the latter is believed to facilitate biosynthesis in the hydrophobic regions of membranes. 

Biosynthesis in C. m. Plants are the main producers of carbohydrates in nature. In photosynthesis, a series of enzymatic reactions (the dark reactions of photosynthesis) produces phosphorylated monosaccharide derivatives, which can be hyc lysed to bee sugars or converted to Nucleoside diphosphate sugars (see). 

CDP-sugars cytidine disphosphate sugars, a meta-bolically activated form of sugars and sugar derivatives (see Nucleoside diphosphate sugars). CDP-ribi-tol, is a precursor in the biosynthesis of bacterial cell walls. 

Cytidine phosphates cytidine S -monophosphate (CMP, cytidylic acid, M, 323.2), cytidine 5 -diphos-phate (CDP, M, 403.19) and cytidine 5 -triphosphate (CTP, M, 483.16). For structure, see e. g. Pyrimidine biosynthesis. CTP is a precursor of RNA synthesis, while deoxy-CTP is a precursor of DNA synthesis. CDP may be regarded as the coenzyme of phospholipid biosynthesis (see Membrane lipids) (activated choline is CDP-choline). Glycerol and the sugar alcohol, ribitol, are also activated by bonding to CDP (see Nucleoside diphosphate sugars). Reduction of ribose... 

Whitesides and coworkers have carried out a comparison of enzymic and chemical routes to CTP, GTP and UTP on a 10-gram scale. They concluded that CTP and GTP were best made enzymically, and UTP by reaction of CTP with nitrous acid. The triphosphates were then employed for the enzymic synthesis of UDP-Glucose, UDP-Glucuronic acid, and GDP-Mannose.i94 Cytidine diphosphate sugars have been prepared from the 3,6-dideoxyhexoses paratose and abequose,193 and all four nucleoside diphosphate sugars of 6-sulpho-a-D-quinovose have been synthesized for studies of sulpholipid biosynthesis in chloroplasts.196 The stable analogue (138) of CMP-KDO has been prepared by a triester approach, but was only a weak inhibitor of KDO incorporation into lipopolysaccharides.197 A reference to acetylated forms of UDPGlc is mentioned in Chapter 7. 

This intermediate is unusual for two reasons. First, other intermediates in oligosaccharide biosynthesis involve nucleoside diphosphates (such as UDP-Glucose). Second, CMP-sialic acid is synthesized in the nucleus of animal cells, whereas all other known nucleotide-linked sugars are synthesized in the cytosol. 

For most of the sugar components, little or nothing is known about their biosynthesis. Nucleoside hexosyl-4-ulose diphosphates are, however, almost certainly key intermediates in the biosynthesis of several of these sugars, as discussed in Ref 7. The biosynthesis of the 6-deoxyheptoses is probably analogous to that of the 6-deoxyhexoses, and proceeds by way of nucleoside heptosyl-4-ulose diphosphates. 

The sugar nucleotides (an uninformative name that has been used for glycosyl nucleotides, or more strictly, glycosyl esters of nucleoside di- or mono-phosphates) were discussed in this Series12 in 1973. Since then, accumulation of new data about these derivatives has continued, and now, about 35 representatives of this class are known to participate in the biosynthesis of polysaccharide chains of bacterial polymers (for a survey, see Ref. 13). These include glycosyl esters of uridine 5 -diphosphate (UDP), thymidine 5 -diphosphate (dTDP), guanosine 5 -diphosphate (GDP), cytidine 5 -diphosphate (CDP), cytidine 5 -monophosphate (CMP), and adenosine 5 -diphosphate (ADP). 

The key intermediates in the biosynthesis of 6-deoxy sugars are the nucleoside 6-deoxyhexosyl-4-ulose diphosphates (7), formed through enzymic reactions catalyzed by NDP-sugar 4,6-dehydratases (EC 4.2.1.45-47) from primary glycosyl nucleotides. These reactions were observed... 

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