Quantifying interactions within the NADP(H) enzyme network in Drosophila melanogaster

Thomas J S Merritt, Caitlin Kuczynski, Efe Sezgin, Chen Tseh Zhu, Seiji Kumagai, Walter F. Eanes

Research output: Contribution to journalArticle

Abstract

In this report, we use synthetic, activity-variant alleles in Drosophila melanogaster to quantify interactions across the enzyme network that reduces nicotinamide adenine dinucleotide phosphate (NADP) to NADPH. We examine the effects of large-scale variation in isocitrate dehydrogenase (IDH) or glucose-6-phosphate dehydrogenase (G6PD) activity in a single genetic background and of smaller-scale variation in IDH, G6PD, and malic enzyme across 10 different genetic backgrounds. We find significant interactions among all three enzymes in adults; changes in the activity of any one source of a reduced cofactor generally result in changes in the other two, although the magnitude and directionality of change differs depending on the gene and the genetic background. Observed interactions are presumably through cellular mechanisms that maintain a homeostatic balance of NADPH/NADP, and the magnitude of change in response to modification of one source of reduced cofactor likely reflects the relative contribution of that enzyme to the cofactor pool. Our results suggest that malic enzyme makes the largest single contribution to the NADPH pool, consistent with the results from earlier experiments in larval D. melanogaster using naturally occurring alleles. The interactions between all three enzymes indicate functional interdependence and underscore the importance of examining enzymes as components of a network.

Original languageEnglish (US)
Pages (from-to)565-574
Number of pages10
JournalGenetics
Volume182
Issue number2
DOIs
StatePublished - Jun 2009
Externally publishedYes

ASJC Scopus subject areas

  • Genetics

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    Merritt, T. J. S., Kuczynski, C., Sezgin, E., Zhu, C. T., Kumagai, S., & Eanes, W. F. (2009). Quantifying interactions within the NADP(H) enzyme network in Drosophila melanogaster. Genetics, 182(2), 565-574. https://doi.org/10.1534/genetics.109.100677