Discovery of an alternate metabolic pathway for urea synthesis in adult Aedes aegypti mosquitoes
Autor(es): Scaraffia, Patricia Y.; Tan, Guanhong; Isoe, Jun; Wysocki, Vicki H.; Wells, Michael A.; Miesfeld, Roger L.
Resumo: We demonstrate the presence of an alternate metabolic pathway for urea synthesis in Aedes aegypti mosquitoes that converts uric acid to urea via an amphibian-like uricolytic pathway. For these studies, female mosquitoes were fed a sucrose solution containing super(15)NH sub(4)Cl, [5- super(15)N]-glutamine, [ super(15)N]-proline, allantoin, or allantoic acid. At 24 h after feeding, the feces were collected and analyzed in a mass spectrometer. Specific enzyme inhibitors confirmed that mosquitoes incorporate super(15)N from super(15)NH sub(4)Cl into [5- super(15)N]-glutamine and use the super(15)N of the amide group of glutamine to produce labeled uric acid. More importantly, we found that [ super(15)N sub(2)]-uric acid can be metabolized to [ super(15)N]-urea and be excreted as nitrogenous waste through an uricolytic pathway. Ae. aegypti express all three genes in this pathway, namely, urate oxidase, allantoinase, and allantoicase. The functional relevance of these genes in mosquitoes was shown by feeding allantoin or allantoic acid, which significantly increased unlabeled urea levels in the feces. Moreover, knockdown of urate oxidase expression by RNA interference demonstrated that this pathway is active in females fed blood or super(15)NH sub(4)Cl based on a significant increase in uric acid levels in whole-body extracts and a reduction in [ super(15)N]-urea excretion, respectively. These unexpected findings could lead to the development of metabolism-based strategies for mosquito control.
Palavras-Chave: Nitrogen metabolism; RNA Interference
Imprenta: Proceedings of the National Academy of Sciences of the United States of America, v. 105, n. 2, p. 518-523, 2008.
Descritores: Aedes aegypti - RNA ; Aedes aegypti - Public health
Data de publicação: 2008
