Presenting Author Vassar College east meadow, New York
Phosphoglycolate phosphatase (PGP) and pyridoxal phosphate phosphatase (PDXP) are members of the haloacid dehalogenase (HAD) family of non-protein phosphatases. PGP plays an important role in central carbon metabolism by regulating glycolysis, the pentose phosphate pathway, and lipid metabolism. PGP also acts as a metabolite repair enzyme by cleaning up toxic side products from glyceraldehyde 3-phosphate dehydrogenase, pyruvate kinase, and DNA repair. PDXP regulates pyridoxal phosphate (PLP; active vitamin B6), a cofactor for 140+ enzymes. Although previous studies have characterized PGP and PDXP in mammals, their fly orthologs remain unidentified. Here, we use mutagenesis and transgenic tools to investigate the putative PGP and PDXP orthologs in the fruit fly D. melanogaster, CG5567 and CG5577. We found that CG5567 mutants survive to adulthood, unlike mice lacking PGP, but they are sensitive to ethylene glycol and have increased triglyceride levels, consistent with previous studies showing that mammalian PGP de-phosphorylates phosphoglycolate and glycerol-3-phosphate. CG5567 mutants are also more resistant to starvation. CG5577 mutants also survive to adulthood but do not share these phenotypes. However, flies overexpressing CG5577 die as late third instar larvae. We are currently testing if we can rescue the CG5577 overexpression phenotype by increasing PLP levels. Additionally, we are using mass spectrometry to analyze substrate and product levels to confirm that CG5567 and CG5577 are functioning as PGP and PDXP orthologs. Our results demonstrate that D. melanogaster is a useful model for investigating the function and evolution of PGP and PDXP.
