In mammalian cells, a major role of UDP-glucose is as the glucosyl donor for the synthesis of the storage polysaccharide glycogen [11] and [12]. Therefore, an active UDP-glucose pyrophosphatase would have the potential to influence or even regulate the flux of
Angiotensin I into glycogen (Fig. 1). Although such a mechanism to regulate UDP-glucose would be energetically expensive, there are many examples where benefit to the cell must outweigh the energetic expense of operating so-called “futile cycles”. In this regard, it would be of interest to know the distribution of the UGPPase in mammalian tissues, one goal of the present study. Some support for an involvement of Nudix hydrolase in polysaccharide metabolism comes from other organisms. In plants,
glucose is stored as starch, a polysaccharide chemically similar to glycogen, but in this case the glucosyl donor is ADP-glucose [13], [14], [15] and [16]. Recent studies have identified an ADP-glucose pyrophosphatase that, analogously to UGPPase, has been proposed to control ADP-glucose levels, and hence starch accumulation, in some tissues [17] and [18]. In Escherichia coli, an ADP-glucose pyrophosphatase, encoded by the NudF (aspP) gene, has been reported to regulate ADP-glucose levels linked to bacterial glycogen synthesis [19].
