Female mosquitoes require a blood meal from a vertebrate host to produce eggs. The public health importance of mosquitoes derives from the fact that while obtaining such a blood meal from a human host the mosquito is able to transmit diseases, such as malaria and dengue, which world-wide are responsible for millions of deaths per year. We need to significantly increase our understanding of the biology of mosquitoes. One area that has been neglected, so far, is fundamental metabolic studies directed towards understanding how the female mosquito utilizes the components of the blood meal. At most 20 percent of the blood meal amino acids are used for egg production and the purpose of this proposal is determine the fate of the other 80 percent. Thus, this proposal is concerned with following the fate amino acids derived from blood meal proteins under a variety of nutritional states. In addition, we propose to assess the role of preexisting energy reserves in the female mosquito during blood meal utilization. Once the relevant pathways have been defined, future studies will be concerned with mechanisms that regulate the pathways under different nutritional, behavioral and environmental conditions. In this proposal we plan to quantitatively examine the fate of amino acids derived from blood meal proteins in Aedes aegypti, the vector of dengue fever and Anopheles albimanus, a vector of malaria in Central and South America. The following specific aims are proposed: 1. Determine the metabolic fate of 14C-labeled blood meal protein amino acids. 2. Determine the metabolic fate of preexisting energy stores, specifically glycogen and lipid, following a blood meal. 3. Characterize the metabolism of blood meal protein amino acids.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI046541-03
Application #
6628019
Study Section
Special Emphasis Panel (ZRG1-TMP (01))
Program Officer
Aultman, Kathryn S
Project Start
2001-02-15
Project End
2006-01-31
Budget Start
2003-02-01
Budget End
2004-01-31
Support Year
3
Fiscal Year
2003
Total Cost
$300,425
Indirect Cost
Name
University of Arizona
Department
Biochemistry
Type
Schools of Arts and Sciences
DUNS #
806345617
City
Tucson
State
AZ
Country
United States
Zip Code
85721
Isoe, Jun; Stover, Weston; Miesfeld, R Barrett et al. (2013) COPI-mediated blood meal digestion in vector mosquitoes is independent of midgut ARF-GEF and ARF-GAP regulatory activities. Insect Biochem Mol Biol 43:732-9
Mack, Daniel J; Isoe, Jun; Miesfeld, Roger L et al. (2012) Distinct biological effects of golgicide a derivatives on larval and adult mosquitoes. Bioorg Med Chem Lett 22:5177-81
Alabaster, Amy; Isoe, Jun; Zhou, Guoli et al. (2011) Deficiencies in acetyl-CoA carboxylase and fatty acid synthase 1 differentially affect eggshell formation and blood meal digestion in Aedes aegypti. Insect Biochem Mol Biol 41:946-55
Isoe, Jun; Collins, Jennifer; Badgandi, Hemant et al. (2011) Defects in coatomer protein I (COPI) transport cause blood feeding-induced mortality in Yellow Fever mosquitoes. Proc Natl Acad Sci U S A 108:E211-7
Scaraffia, Patricia Y; Zhang, Qingfen; Thorson, Kelsey et al. (2010) Differential ammonia metabolism in Aedes aegypti fat body and midgut tissues. J Insect Physiol 56:1040-9
Jiang, Wei; Wysocki, Vicki H; Dodds, Eric D et al. (2010) Differentiation and quantification of C1 and C2 (13)C-labeled glucose by tandem mass spectrometry. Anal Biochem 404:40-4
Zhou, Guoli; Miesfeld, Roger L (2009) Energy metabolism during diapause in Culex pipiens mosquitoes. J Insect Physiol 55:40-6
Scaraffia, Patricia Y; Tan, Guanhong; Isoe, Jun et al. (2008) Discovery of an alternate metabolic pathway for urea synthesis in adult Aedes aegypti mosquitoes. Proc Natl Acad Sci U S A 105:518-23
Scaraffia, Patricia Y; Zhang, Qingfen; Wysocki, Vicki H et al. (2006) Analysis of whole body ammonia metabolism in Aedes aegypti using [15N]-labeled compounds and mass spectrometry. Insect Biochem Mol Biol 36:614-22
Zhang, Qingfen; Wysocki, Vicki H; Scaraffia, Patricia Y et al. (2005) Fragmentation pathway for glutamine identification: loss of 73 Da from dimethylformamidine glutamine isobutyl ester. J Am Soc Mass Spectrom 16:1192-203

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