This research will examine how two mutant enzyme variants, found in natural populations, influence an important metabolic pathway. As a model system the study focuses on the enzyme glucose-6-phosphate dehydrogenase (G6PD) in the fruit fly, Drosophila melanogaster. Prior studies have indicated significant differences in biochemical properties, but it is unclear that these differences as determined in the test tube in vitro reflect how the genetic variants function in the living fly (in vivo). This question will be addressed by examining the amount of radioactively labelled glucose passed through the metabolic pathway in flies possessing either genetic variant of the enzyme. This test is essential to our understanding of naturally occurring enzyme variation because it is usually assumed that there is a one-to-one correspondence between artificial in vitro measures of biochemical function and their function in vivo. However, no direct experiments have ever been conducted to test this assumption. This is the crucial experimental examination of that assumption in one of the very few systems where it may be directly tested.
