Glucose-6-phosphatase-beta (G6PC3) is a ubiquitous phosphatase present in the endoplasmic
reticulum, which, unlike G6PC1, is not responsible for maintaining blood glucose level
under starvation. Recently, G6PC3 has been shown to play an important role in neutrophil
granulocytes, eliminating the toxic metabolite 1,5-anhydroglucitol-6-phosphate. The
present study aimed to look for alternative substrates for the enzyme and outline
the expression changes in the parts of this multicomponent system during neutrophil
granulocyte differentiation. We determined the kinetic characteristics of recombinant
human G6PC3 towards different sugar phosphates, and the transport of these compounds
was also measured in rat liver microsomes. We found that all investigated sugar phosphates
are substrates for G6PC3, although their microsomal transport is much slower than
that of glucose-6-phosphate. Using the HL-60 promyelocytic leukemia cell line as an
in vitro model system for myeloid differentiation, we found no significant differences
in enzyme expression and phosphatase activity latency between undifferentiated and
differentiated cells. Our results provide novel insights into the possible role of
G6PC3 in the dephosphorylation of alternative sugar phosphates or their metabolites
synthesized in the endoplasmic reticulum and confirm the potential feature of the
enzyme in the promyelocytic stage as well. These findings contribute to our knowledge
of intracellular carbohydrate metabolism of neutrophil granulocytes, which facilitates
further research directions to better understand the underlying mechanisms of neutropenias.
