TY - JOUR T1 - UDP-Galactose 4′-Epimerase Activities toward UDP-Gal and UDP-GalNAc Play Different Roles in the Development of Drosophila melanogaster A1 - Daenzer, Jennifer M. I. A1 - Sanders, Rebecca D. A1 - Hang, Darwin A1 - Fridovich-Keil, Judith L. Y1 - 2012/05/24 N2 - Author Summary In this manuscript we apply a fruit fly model to explore the relative contributions of each of two different activities attributed to a single enzyme—UDP-galactose 4′-epimerase (GALE); partial impairment of human GALE results in the potentially severe metabolic disorder epimerase deficiency galactosemia. One GALE activity involves interconverting UDP-galactose and UDP-glucose in the Leloir pathway of galactose metabolism; the other activity involves interconverting UDP-N-acetylgalactosamine and UDP-N-acetylglucosamine. We have previously demonstrated that complete loss of GALE is embryonic lethal in fruit flies, but it was unclear which GALE activity loss was responsible for the outcome. Using genetically modified fruit flies, we were able to remove or give back each GALE activity individually at different times in development and observe the consequences. Our results demonstrate that both GALE activities are essential, although they play different roles at different times in development. These results provide insight into the normal functions of GALE and also have implications for diagnosis and intervention in epimerase deficiency galactosemia. JF - PLOS Genetics JA - PLOS Genetics VL - 8 IS - 5 UR - https://doi.org/10.1371/journal.pgen.1002721 SP - e1002721 EP - PB - Public Library of Science M3 - doi:10.1371/journal.pgen.1002721 ER -