Pyrophosphorylase

Pyrophosphorylase refers to a group of enzymes that catalyze the formation of nucleoside diphosphate (NDP) sugars by transferring a pyrophosphoryl group from a nucleoside triphosphate to a sugar phosphate, releasing pyrophosphate (PPi). Members of this family are essential for the biosynthesis of polysaccharides and glycoconjugates, providing activated sugar donors for downstream glycosyltransferases.

The best-known examples are ADP-glucose pyrophosphorylase (AGPase) and UDP-glucose pyrophosphorylase (UGPase). AGPase converts ATP and glucose-1-phosphate into ADP-glucose and PPi and is a key regulatory step in starch biosynthesis in plants and some microbes. UGPase catalyzes the formation of UDP-glucose from UTP and glucose-1-phosphate, supplying UDP-glucose for cellulose, callose, and other glycan biosynthetic pathways, as well as nucleotide sugar donors for glycosylation reactions. Other NDP-sugar pyrophosphorylases, such as GDP-mannose pyrophosphorylase, generate GDP-sugars used in cell wall and glycoprotein biosynthesis.

Mechanistically, these enzymes typically form a complex with the sugar-1-phosphate and the nucleotide triphosphate to produce the corresponding NDP-sugar and PPi. In many organisms, PPi hydrolysis by pyrophosphatases helps pull the reaction forward, increasing net flux toward NDP-sugar production.

Regulation and evolution vary by organism. In plants, AGPase is often allosterically regulated by metabolites such as 3-phosphoglycerate and inorganic phosphate, linking carbon metabolism to starch production. The enzymes are widespread in bacteria, archaea, and eukaryotes, reflecting their central role in the formation of activated sugar donors for diverse polysaccharides.