Fermentation and nucleotide-sugars: a long history

It was exactly 101 years ago, while working on fermentation of sugars by yeast, that Harden and Young (408) first reported the chemistry and metabolic roles of sugar-phosphates. Later, different types of sugar kinases from yeast, muscle, and plant sources were identified that were able to convert sugar (monosaccharide) and ATP to the phosphorylated-sugar esters. The seminal work by Cori et al. in 1939 (409) proved, for the first time, the role of sugar-phosphates in the synthesis of polysaccharides (i. e., glycogen). Since the discovery of UDP-glucose in yeast (410), which was followed by the isolation of other NDP-sugars in yeast, plants, bacteria, algae, and humans, it has become apparent that NDP-sugars are the prime sugar-substrates used in the biosynthesis of glycans. The biosynthesis of activated- sugars is achieved in three general ways.

2.5.1 Sugar kinase — pyrophosphorylase pathway to synthesize NDP-sugars

Some sugars are first converted directly, or in a series of enzymatic steps, to phospho-1- sugars in the presence of ATP.

Sugar + ATP ^ Sugar-1-P + ADP

Following the phosphorylation of the anomeric center, enzymes known as pyrophos — phorylases transfer a nucleotide-monophosphate from NTP to the sugar-1-P to form the NDP-sugar. The synthesis of UDP-Glc and GDP-Man are examples of this type of synthesis.