A recent in vitro characterization of a recombinant?pyruvate?kinase (PK) from?Aedes?aegypti?mosquitoes?demonstrated that the enzyme is uniquely regulated by multiple allosteric effectors. Here, we further explored PK gene and protein expression, and enzymatic activity in key?metabolic?tissues of?mosquitoes?maintained under different nutritional conditions. We also studied the?metabolic?effects of PK depletion using several techniques including RNA interference and?mass?spectrometry-based?stable-isotope?tracing. Transcriptional analysis showed a dynamic post-feeding PK mRNA expression pattern within and across mosquito tissues, whereas corresponding protein levels remained stable throughout the time course analyzed. Nevertheless, PK activity significantly differed in the fat body of sucrose-, blood-fed, and starved?mosquitoes. Genetic silencing of PK did not alter survival in blood-fed females maintained on sucrose. However, an enhanced survivorship was observed in PK-deficient females maintained under different nutritional regimens. Our results indicate that?mosquitoes?overcame PK deficiency by up-regulating the expression of genes encoding NADP-malic enzyme-1, phosphoenolpyruvate carboxykinase-1, phosphoglycerate dehydrogenase and glutamate dehydrogenase, and by decreasing glucose oxidation and?metabolic?pathways associated with ammonia detoxification. Taken together, our data demonstrate that PK confers to A.?aegypti?a?metabolic?plasticity to tightly regulate both carbon and nitrogen metabolism.