Direct Measurement of in Vivo Flux Differences between Electrophoretic Variants of G6pd from Drosophila Melanogaster

AUTOR(ES)

Labate, J.

RESUMO

Demonstrating that naturally occurring enzyme polymorphisms significantly impact metabolic pathway flux is a fundamental step in examining the possible adaptive significance of such polymorphisms. In earlier studies of the glucose-6-phosphate dehydrogenase (G6PD) polymorphism in Drosophila melanogaster, we used two different methods, exploiting both genotype-dependent interactions with the 6Pgd locus, and conventional steady-stake kinetics to examine activity differences between the two common allozymes. In this report we use 1-(14)C- and 6-(14)C-labeled glucose to estimate directly genotype-dependent flux differences through the pentose shunt. Our results show the G6pd(A) genotype possesses statistically lower pentose shunt flux than G6pd(B) at 25°. We estimate this to be about a 32% reduction, which is consistent with the two former studies. These results reflect a significant responsiveness of pentose shunt flux to activity variation at the G6PD-catalyzed step, and predict that the G6PD allozymes generate a polymorphism for pentose shunt flux.

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