Spring 2002 Catalyst


By Michael A. Wells, PhD, Regents Professor

Female mosquitoes require the amino acids in blood proteins to mature their eggs. It is during the process of taking blood that the mosquito can transmit diseases such as malaria and Dengue fever, which are reemerging as very significant health problems. Of interest to us is the fact that at the moment the blood meal is ingested the female is not able to digest the proteins because she has no active trypsin in her gut. For several years we have been working to understand the complex mechanisms by which blood feeding induces trypsin synthesis. In the first four-six hours following a blood meal, the female gut produces a special type of trypsin called early trypsin. Although only small amounts of early trypsin are made, the activity of early trypsin plays a vital role in the regulation of digestive enzyme synthesis by the gut. Somehow early trypsin, acting on the meal proteins, produces a signal that induces translation of the several proteolytic enzymes required for blood meal protein digestion. The nature of this signal, which is not free amino acids, remains a secret that the mosquito has refused to share despite many attempts to identify it. The synthesis of early trypsin itself is regulated in a unique manner. Transcription of the early trypsin gene starts a few hours after the adult emerges from the pupal state. However, the early trypsin mRNA is stored in the midgut epithelium and remains untranslated until a blood meal is taken. It seems that free amino acids in the blood are the signal for translation, apparently by providing amino acids to charge tRNAs in the gut, which in the absence of a blood meal are uncharged, thereby limiting translation. Thus, early trypsin is part of a fascinating signaling system that conveys the presence of protein in the gut lumen to the epithelial cell. Once the signal is received, the epithelial cells can produce the enzymes required for protein digestion; in the absence of the signal the cell is quiescent. These regulatory mechanisms ensure that proteases are made only when needed.Given the importance of amino acids for producing the proteins of the egg, one might suspect that the mosquito would be quite efficient in using the amino acids. In fact, the contrary is true. She uses less only 10-15% of the amino acids to make egg proteins. Some of the rest are used to make egg lipids, and some are used to build energy reserves of the female. But more than 80% of the amino acid carbon is oxidized to CO2 to provide the energy needed for egg production. We are studying the partitioning of the meal proteins into various products and are especially interested in how the nutritional state of the female affects these processes. It is probable that females who had poor larval nutrition will need more than one blood meal to mature a batch of eggs, because the first or even the second meal is needed to build up the energy reserves needed to produce eggs. Under such circumstances the possibility of disease transmission increases, so it becomes important to understand how the female manages the blood meal Because the female oxidizes 80% of the amino acids, she has a very large amount of ammonia to deal with. We have discovered that she places the ammonia in proline, which she stores in her hemolymph (blood), until she can convert the ammonia to urea or uric acid for secretion. This is a unique process in mosquitoes and the hemolymph proline concentration can be as high as 80 mM. We have proposed a proline cycle to describe this process.

Graphic of proline cycle

Biological Sciences West
P.O. Box 210088 ·Tucson, AZ 85721-0088
Tel: (520) 621-9185 FAX (520) 621-9288
Department of Biochemistry and Molecular Biophysics
The University of Arizona
Updated June 1, 2004

http://www.biochem.arizona.edu/
All contents copyright ©2002. All rights reserved.
cherylr@u.arizona.edu