Pyridoxine/pyridoxamine 5′‐phosphate oxidase (Sgll/PNPO)is important for DNA integrity and glucose homeostasis maintenance in Drosophila
Pyridoxine/pyridoxamine 5′‐phosphate oxidase (PNPO) and pyridoxal kinase (PDXK)
cooperate to produce pyridoxal 5′‐phosphate (PLP), the active form of vitamin B6. PDXK
phosphorylates pyridoxine, pyridoxamine, and pyridoxal by producing PNP, PMP, and PLP,
whereas PNPO oxidizes PNP, PMP, into PLP. We previously demonstrated that PDXK
depletion in Drosophila and human cells impacts on glucose metabolism and DNA integrity.
Here we characterized sgll, the Drosophila ortholog of PNPO gene, showing that its silencing
by RNA interference elicits chromosome aberrations (CABs) in brains and induces diabetic
hallmarks such as hyperglycemia and small body size. We showed that in sgllRNAi
neuroblasts CABs are largely produced by the genotoxic effect of the advanced glycation
end products triggered by high glucose. As in sgllRNAi cells, part of PLP is still produced by
PDXK activity, these data suggest that PLP dosage need to be tightly regulated to
guarantee glucose homeostasis and DNA integrity