Abstract:
The current study focuses on the preliminary characterization of a purine nucleotide cycle enzyme, AMP deaminase (AMPD hereafter) and members of the Haloacid Dehalogenase superfamily (HADSF) from Plasmodium falciparum and Plasmodium berghei. Purine nucleotide cycle performs inter-conversion of IMP and AMP with the release of fumarate and ammonia as byproducts, that have physiological consequences. The pathway also plays a chief role in maintaining the adenylate energy charge (AEC) ratio, which is critical for cell survival (Chapman and Atkinson, 1973). This is achieved by regulating the levels of AMP. AMPD is a catabolic enzyme which deaminates AMP to IMP that can be further channelized to GMP production or AMP synthesis depending on the cellular requirement for respective mononucleotides. AMP can also be catabolized to adenosine and inorganic phosphate by specific/promiscuous 5´ nucleotidases, which are a common occurrence in the HAD superfamily. In a cellular context, AMP can be regarded as the central hub for the regulation of AEC. AMP deaminase, as well as nucleotidases, play a key role in maintaining the levels of this metabolite (Fig. 1). Failure in the regulation of AMP levels
results in accumulation of this metabolite which has been shown to inhibit the de novo purine biosynthetic pathway that subsequently leads to defective protein synthesis (Akizu et al., 2013). AMP accumulation also drives the adenylate kinase reaction in the direction towards ATP depletion, which is physiologically not productive. Given the importance of nucleotide metabolism in the malarial parasite, it becomes imperative to have a substantial understanding of the modes and players involved in the regulation of nucleotide levels. Here, we have made an attempt to understand the role of AMPD and putative nucleotidases belonging to HAD superfamily from the parasitic protozoan Plasmodium.
