Sugar nucleotides principle

Epimerases and racemases may or may not employ enzyme cofactors (organic or inorganic) to activate the stereogenic center of the substrate. Common cofactor-stabilized intermediates include resonance-stabilized carbanions and metal-stabilized enolates. The substrate itself can be intrinsically activated if the stereogenic center is adjacent to a carbonyl or carboxylate group. A preponderance of racemases and epimerases act on activated substrates. A number of sugar and sugar nucleotide epimerases act on unactivated substrates. Double proton transfers may proceed, in principle, by either a one- or two-base mechanism. However, only two-base mechanisms have been observed for racemases. 

Defects in glycosyltransferase activity or availability of sugar nucleotide are not the only possible causes of incompletion in saccharide sequences. In principle, a failure to bring the enzyme and its substrates together would have the same effect. An instance of the latter has been shown by Reitman et al. (1980) who found a mutant cell line in which there was a deficit of fucosyl residues, without any lack of donor, acceptor or enzyme (see Chapter 4). Synthesis would occur in cell-firee homogenates, but not in intact cells. There was clearly a misapproximation of the reactants, but the cause of it is unknown. 

We shall begin with compounds whose biosynthesis requires sucrose as primer just like that of the oligosaccharides mentioned above. Subsequently, we shall discuss other polysaccharides whose biosynthesis does not start with sucrose. However, even with these substances we shall come across well-known principles again, such as the transfer of a sugar from a sugar nucleotide to a particular primer,... 

Finally, transport can also be driven by the conversion of intracellular substrate to another chemical form. For example, in the case of nucleoside drugs, conversion to the corresponding nucleotides by appropriate kinases may be the limiting factor in cellular uptake and activation. The same principle applies to sulfation, glu euro nidation, prodrug activations, or other metabolic processes that provide a removal of the transported species from the transportable (free) internal pool. In some cases, transport is directly coupled to substrate modification, as in the uptake of sugars into bacterial cells by phosphoenolpyruvate (PEP)-coupled phosphorylation systems. 

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