Interactions of NADP-Reducing Enzymes Across Varying Environmental Conditions: A Model of Biological Complexity

Abstract

Interactions across biological networks are often quantified under a single set of conditions; however, cellular behaviors are dynamic and interactions can be expected to change in response to molecular context and environment. To determine the consistency of network interactions, we examined the enzyme network responsible for the reduction of nicotinamide adenine dinucleotide phosphate (NADP) to NADPH across three different conditions: oxidative stress, starvation, and desiccation. Synthetic, activity-variant alleles were used in Drosophila melanogaster for glucose-6-phosphate dehydrogenase (G6pd), cytosolic isocitrate dehydrogenase (Idh), and cytosolic malic enzyme (Men) along with seven different genetic backgrounds to lend biological relevance to the data. The responses of the NADP-reducing enzymes and two downstream phenotypes (lipid and glycogen concentration) were compared between the control and stress conditions. In general, responses in NADP-reducing enzymes were greater under conditions of oxidative stress, likely due to an increased demand for NADPH. Interactions between the enzymes were altered by environmental stress in directions and magnitudes that are consistent with differential contributions of the different enzymes to the NADPH pool: the contributions of G6PD and IDH seem to be accentuated by oxidative stress, and MEN by starvation. Overall, we find that biological network interactions are strongly influenced by environmental conditions, underscoring the importance of examining networks as dynamic entities.

High sucrose consumption promotes obesity whereas its low consumption induces oxidative stress in Drosophila melanogaster

“…It well corresponds to our data showing higher IDH activity in males when compared to females. Our findings might also indicate a general need in males for maintenance of high NADPH pool and functional relationship between NADPH producing enzymes reported previously (Rzezniczak and Merritt, 2012). Since G6PDH and IDH are tightly related to antioxidant function of glutathione, it may explain higher GST activity in males compared to females.…”

“…Simultaneously, NADPH produced in the reaction catalyzed by G6PDH can also be utilized for lipid and sterol synthesis. Moreover, G6PDH is considered to be a lipogenic enzyme (Rzezniczak and Merritt, 2012) and a target of sterol regulatory element binding protein (SREBP) and carbohydrate responsive element binding protein (ChREBP) (Horton et al, 2002;Ma et al, 2006). The first one is shown to be up-regulated by IS (Horton et al, 2002).…”

Seasonal changes in recombination rate, crossover interference, and their response to desiccation stress in a natural population ofDrosophila melanogasterfrom India

“…These include genes whose products are involved in oxidation/reduction processes (intervals pr-c and th-sr) and stresssignalling (interval c-px). This result is in line with the well-recognized role of oxidation/reduction in the acute adaptive response to desiccation stress, including in D. melanogaster [76,77]. Remarkably, genome regions closed to intervals pr-c and th-sr demonstrated pronounced RR plasticity also to heat [26].…”

The impact of metagenomic interplay on the mosquito redox homeostasis

“…In addition to the enzymes G6PD and 6-phosphogluconate dehydrogenase (6PGD) in PPP, cytosolic isocitrate dehydrogenase (IDH) and cytosolic malic enzyme (MEN) are two other enzymatic players in a concerted metabolic network for the reduction of NADP + to NADPH. This network coordinates metabolic responses to various environmental stress, such as oxidative stress, starvation, and desiccation [61]. In Aedes mosquitoes, metabolic genes are responsive to blood intake.…”