Adenosine nucleosides in Trypanosoma cruzi: adenylate kinases and related enzymes.

BOUVIER, LEON; MIRANDA, MARIANA; CANEPA, GASPAR; PEREIRA, CA

Mendoza

Congreso; VII Congreso Argentino de Protozoología y Enfermedades Parasitarias; 2005

Adenylate kinases supply energy routes in cellular energetic homeostasis by interconversion of constituents of the adenine nucleotide pool. Our group has identified and characterized six T. cruzi adenylate kinase isoforms with a wide range of predicted subcellular localizations, including: flagellum, mitochondria, glycosome and cytosol. In addition, an unusual adenlate kinase sequence similar to the nuclear AdK6 (human) was detected in the T. cruzi genome. One of the key sensors of the ATP:AMP ratios in eukariotic organisms are the AMP-dependent protein kinases (AMPKs). If the rate of ATP consumption in a cell exceeds its rate of production, ADP will tend to rise and be converted to AMP by the adenylate kinase. The rise in level of the activating ligand AMP, coupled with the fall in level of the inhibitory nucleotide ATP, activates AMPK, which then switches off ATP-consuming processes and switches on catabolism in an attempt to redress the balance. As a first step to study this process in T. cruzi we have identified and cloned a putative AMPK composed by a catalitic subunit (alpha) and two regulatory subunits (beta and gamma), which are now under characterization.