International Research Journal of Advanced Engineering and Science ISSN (Online): 2455-9024 188 J. O. Assor, V. I. Nnamani, O. N. Osita, O. I Diyoke, S. Cosmas, and O. A Durojaye, “Comparative Genome Analysis of Plasmodium falciparum Triosephosphate Isomerase and Cytochrome Oxidase; Effect of Antimalarial Drugs on the Enzyme Stability,” International Research Journal of Advanced Engineering and Science, Volume 3, Issue 3, pp. 188-193, 2018. Comparative Genome Analysis of Plasmodium falciparum Triosephosphate Isomerase and Cytochrome Oxidase; Effect of Antimalarial Drugs on the Enzyme Stability J. O. Assor 1 , V. I. Nnamani 2 , O. N. Osita 3 , O. I. Diyoke 4 , S. Cosmas 5 , *O. A. Durojaye 6 1, 2, 3, 4, 5, 6 Department of Biochemistry, University of Nigeria, Nsukka, Enugu State, Nigeria Email address: { 1 johnassor, 2 vyando1000, 3 nelsonosita.sbe, 4 obinnadiyoke}@gmail.com, { 5 Cos242, 6 lanre.durojaye}@yahoo.com Abstract— Background: Malaria is a major global public health challenge. Plasmodium falciparum happens to be the most virulent among the causative parasites of malaria. The development of drug resistance in Plasmodium falciparum strains has built up a great interest in the search for new antimalarial drugs and drug targets. As part of a program to develop metabolic enzymes as potential drug targets, the 3-dimensional structure of Plasmodium falciparum triosephosphate isomerase was determined. The focus on glycolytic and electron transport chain enzymes in the malaria parasite results from the observation that in the asexual stage of the parasite in the human red blood cells, the energy requirements of the organism are almost exclusively met by glycolysis and the electron transport chain enzyme of the parasite remains highly stable and resistant. Materials and Methods: The amino acid sequences of the experimental enzymes were mined from the NCBI database and sequence aligment between the triosephosphate isomerase and cytochrome oxidase of P. falciparum and their respective human orthologs were performed using the ClustalW sequence alignment software. The alignments were visualized using the Bioedit software which is a biological sequence alignment editor. The MEGA7 software was used to view and highlight the protein conserved domains and variable sites while the prediction of the protein domain was done using the PSIPRED. The amino acid composition graph of the P. falciparum enzymes was also plotted using specific functions on the MEGA7 software. Results: Here, we present a computational analysis of the amino acid composition of Plasmodium falciparum triosephosphate isomerase and cytochrome oxidase which are cytosolic and mitochondrial enzymes respectively. An alignment was also carried out with the human orthologs of each of the respective analysed parasite enzyme sequence. This comparison with the human enzymes was used to predict their functional similarity in respect to therapeutic drug design and the predicted potency of the drug for prophylaxis and disease treatment. Conclusions: Antimalarial drugs targeted at the Plasmodium falciparum triosephosphate isomerase tends to act faster compared to the mitochondrial cytochrome oxidase drug target counterparts. The initial takes advantage on the cytosolic instability of the disulfide bonds which has been analysed also to be of a very minute quantity in the enzymes. Keywords— Plasmodium falciparum; Resistance; Alignment; Orthologs; Prophylaxis. I. BACKGROUND Parasitic organisms acquire organic material from their environments and convert this material into energy or their own substance (i.e., biomolecules) [8]. Cells are made up of distinct classes of biomolecules with specific functions. These macromolecules are synthesized from small molecular weight precursors. These precursors are components of interconnected metabolic pathways [25]. The malaria parasite exhibits a fast growth and multiplication rate during many stages of its life cycle. This makes it necessary for the parasite, like all other organisms to acquire nutrients and metabolize these biological molecules in order to survive and reproduce [17]. It is a clear concept that the parasite's metabolism will be intertwined with that of the host's because of the intimate relationship between the host and parasite [13]. These interactions between the host and the parasite are further complicated by the complex life cycle of the parasite involving vertebrate and invertebrate hosts as well as different locations within each of these hosts. A better understanding of the parasite's metabolism may lead to the development of novel therapeutic procedures which exploits the uniqueness of the parasite [13, 27]. The blood-stage of the parasite actively ferments glucose as a primary source of energy. The Plasmodium falciparum metabolic steps involved in the conversion of glucose to lactate are essentially the same as that found in other organisms [25]. All of the enzyme activities in Plasmodium falciparum have been identified including some of the genes which have already been cloned. The parasite exhibits a high rate of glycolysis and utilizes up to 75 times more glucose than uninfected Red blood cells [16, 17]. Most of the glucose is converted to lactate and the high lactate dehydrogenase activity is believed to function in the regeneration of NAD + from NADH which is produced earlier in the glycolytic pathway by glyceraldehyde-3-phophate dehydrogenase. Most of the glucose utilized by the parasite is converted to lactate i.e. an approximate value of 85% of the utilized glucose by the parasite is converted into lactate. However, some of the glycolytic intermediates may be diverted for synthetic purposes. For example, enzymes of the pentose phosphate pathway have been identified. This pathway provides some of the ribose sugars needed for nucleotide metabolism and provides for the regeneration of reduced NADPH to be used in biosynthesis or defense against reactive oxygen species. Similarly, the further metabolism of pyruvate may provide intermediates in several biosynthetic pathways [8].