Quantifying interactions within the NADP(H) enzyme network in Drosophila melanogaster.
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.
Merritt
Thomas J S
TJ
Department of Ecology and Evolution, Stony Brook University, Stony Brook, NY 11794, USA. tmerritt@laurentian.ca
Kuczynski
Caitlin
C
Sezgin
Efe
E
Zhu
Chen-Tseh
CT
Kumagai
Seiji
S
Eanes
Walter F
WF
D000483:Alleles; D000818:Animals; D002875:Chromosomes / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D014644:Genetic Variation; D005838:Genotype; D005954:Glucosephosphate Dehydrogenase / Q000235:genetics / Q000378:metabolism; D007521:Isocitrate Dehydrogenase / Q000235:genetics / Q000378:metabolism; D008291:Malate Dehydrogenase / Q000235:genetics / Q000378:metabolism; D009249:NADP / Q000378:metabolism*; D010084:Oxidation-Reduction; D011485:Protein Binding; D014280:Triglycerides / Q000378:metabolism
D014280:Triglycerides; D009249:NADP; D008291:Malate Dehydrogenase; D007521:Isocitrate Dehydrogenase; D005954:Glucosephosphate Dehydrogenase