Hexoses biosynthesis

U. F., Salah-Bey, K., Benhamou, B., Capdevila, C., Michel, ).M., Piepersberg, W. Raynal, M.C. Analysis of genes involved in 6-deoxy-hexose biosynthesis and transfer in Saccharo-polysporaerythraea. Mol. Gen. Genet. 264, 477-485 (2000). 

Galperin, M. Y., Aravind, L., and Koonin, E. V. (2000). Aldolases of the DhnA family a possible solution to the problem of pentose and hexose biosynthesis in archaea. FEMS Microbiol. Lett. 183, 259-264. 

A rather limited collection of simple precursor molecules is sufficient to provide for the biosynthesis of virtually any cellular constituent, be it protein, nucleic acid, lipid, or polysaccharide. All of these substances are constructed from appropriate building blocks via the pathways of anabolism. In turn, the building blocks (amino acids, nucleotides, sugars, and fatty acids) can be generated from metabolites in the cell. For example, amino acids can be formed by amination of the corresponding a-keto acid carbon skeletons, and pyruvate can be converted to hexoses for polysaccharide biosynthesis. 

Glucose Hexose Glc UDP-GIc Present during the biosynthesis of N-linked glycoproteins but not usually present in mature glycoproteins. Present in some clotting factors. 

The above observations suggested that hexoses arise in Nature by reaction of glycerose with dihydroxyacetone. A vast amount of practical information has been derived from investigation of plant- and muscle-extracts, two dissimilar systems that show many similarities in their biosynthetic manipulations. There is a close parallelism in the sequence of intermediates involved in the processes wherein D-glucose is converted to ethanol and carbon dioxide by yeasts, and to lactic acid by muscle during contraction. The importance of these schemes lies in their reversibility, which provides a means of biosynthesis from small molecules. 

The hexose monophosphate pathway has several names just to confuse you. It s called the hexose monophosphate shunt or pathway (HMP shunt or pathway), or the pentose phosphate pathway, or the phospho-gluconate pathway (Fig. 15-1). The pathway in its full form is complicated and has complicated stoichiometry. Usually it s not necessary to remember all of it. The important points are that it makes NADPH for biosynthesis and riboses (C-5 sugars) for DNA and RNA synthesis. 

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 pathway of the biosynthesis of Neu5Ac demonstrates the origin of sialic acids from the cellular hexose and hexosamine pools. These sugars are, therefore, suitable components for the study of the biosynthesis of sialic acid. However, only ManNAc has been shown to be a relatively specific precursor of sialic acids, as may be seen from the distribution of radioactivity between the individual monosaccharides of glycoconjugates after incubation. Injections of radioactive ManNAc into animals, or incubation of surviving tissue slices or individual cells with this compound, give incorporation of label mainly into the sialic acids.226 227... 

NADPH formed in the oxidative phase is used to reduce glutathione, GSSG (see Box 14-3) and to support reductive biosynthesis. The other product of the oxidative phase is ribose 5-phosphate, which serves as precursor for nucleotides, coenzymes, and nucleic acids. In cells that are not using ribose 5-phosphate for biosynthesis, the nonoxidative phase recycles six molecules of the pentose into five molecules of the hexose glucose 6-phosphate, allowing continued production of NADPH and converting glucose 6-phosphate (in six cycles) to C02. 

Scheme 14 Biosynthesis of the C5 unit of thiamin from isotopically labelled hexoses. Label from D-[l-14C]glucose and D-[l-uC]fructose label C-4 exclusively D-[2-14C]glucose labels C-4 and C-4 equally D-[6-14C]glucose labels C-4 (16% of 14C incorporated the precise location of the remaining 14C was not determined) d-[6-D2]glucose gives rise to both [4 -D2]- and [7-D2]-thiamin...

Figure 17-8 The pentose phosphate pathways. (A) Oxidation of a hexose (C6) to three molecules of C02 and a three-carbon fragment with the option of removing C3, C4, C5, and C7 units for biosynthesis (dashed arrows). (B) Non-oxidative pentose pathways 2 1/2 C6 —> 3 C5 or 2 C6 —> 3 C4 or 3 V2C6 —> 3 C7.

Subsequent Reactions Catalyzing 6-Deoxyhexose Formation 3,5-Epimerase and Reductase. After the formation of the 4-keto intermediate, a step common to all deoxyhexose formations, at least two and possibly three additional enzymes are necessary for the biosynthesis of the end product. This sequence of transformations is illustrated in Figure 3. The first step is the conversion of the 4-keto-6-deoxy-hexose intermediate described above. The intermediates in brackets are postulated and are assumed to be bound to the enzyme. An enzyme (or enzymes), referred to below as 3,5-isomerase, catalyzes epimerizations at carbons 3 and 5, probably via the enediol form. The epimerizations are followed by a... 

Transketolase reactions leading via the pentose or hexose monophosphate shunt pathway of glucose oxidation to the eventual production of pentoses for RNA/DNA synthesis and NADPH for the biosynthesis of fatty acids... 

Because of its roles in the synthesis of glycogen, in isomerization of hexose phosphates, and as a precursor for numerous biosynthetic intermediates, UDP-glucose is regarded as a central hexose derivative in mammalian metabolism. In bacteria and plants, both ADP-glucose (production of storage polysaccharide) and UDP-glucose (sugar interconversions and biosynthesis) play important roles as precursors. 

We discussed the biosynthesis of glucose from simpler starting materials in chapter 12. The biosynthesis of other hex-oses is linked to glucose by a complex network of reactions (fig. 16.2). In fact, glucose serves as the precursor for the synthesis of many other hexoses without any rearrangement of the six carbon core. 

---