Modeling of the Glycolysis Pathway in Plasmodium Falciparum Using Petri Nets

Overview

Journal Bioinform Biol Insights

Publisher Sage Publications

Specialty Biology

Date 2016 May 21

PMID 27199550

Citations 4

Authors

Jelili Oyelade

Itunuoluwa Isewon

Solomon Rotimi

Ifeoluwa Okunoren

Affiliations

Soon will be listed here.

Abstract

Malaria is one of the deadly diseases, which affects a large number of the world's population. The Plasmodium falciparum parasite during erythrocyte stages produces its energy mainly through anaerobic glycolysis, with pyruvate being converted into lactate. The glycolysis metabolism in P. falci-parum is one of the important metabolic pathways of the parasite because the parasite is entirely dependent on it for energy. Also, several glycolytic enzymes have been proposed as drug targets. Petri nets (PNs) have been recognized as one of the important models for representing biological pathways. In this work, we built a qualitative PN model for the glycolysis pathway in P. falciparum and analyzed the model for its structural and quantitative properties using PN theory. From PlasmoCyc files, a total of 11 reactions were extracted; 6 of these were reversible and 5 were irreversible. These reactions were catalyzed by a total number of 13 enzymes. We extracted some of the essential reactions in the pathway using PN model, which are the possible drug targets without which the pathway cannot function. This model also helps to improve the understanding of the biological processes within this pathway.

Citing Articles

Several supplementary concepts for applied category-theoretical states over an extended Petri net using an example relating to genetic coding: Toward an abstract algebraic formulation of molecular/genetic biology.

Sawamura J, Morishita S, Ishigooka J PLoS One. 2024; 19(6):e0302710.

PMID: 38848321 PMC: 11161097. DOI: 10.1371/journal.pone.0302710.

Extracellular vesicles could be a putative posttranscriptional regulatory mechanism that shapes intracellular RNA levels in Plasmodium falciparum.

Kioko M, Pance A, Mwangi S, Goulding D, Kemp A, Rono M Nat Commun. 2023; 14(1):6447.

PMID: 37833314 PMC: 10575976. DOI: 10.1038/s41467-023-42103-x.

Computational Identification of Metabolic Pathways of using the -Shortest Path Algorithm.

Oyelade J, Isewon I, Aromolaran O, Uwoghiren E, Dokunmu T, Rotimi S Int J Genomics. 2019; 2019:1750291.

PMID: 31662957 PMC: 6791207. DOI: 10.1155/2019/1750291.

In Silico Knockout Screening of Reactions and Prediction of Novel Essential Reactions by Analysing the Metabolic Network.

Oyelade J, Isewon I, Uwoghiren E, Aromolaran O, Oladipupo O Biomed Res Int. 2018; 2018:8985718.

PMID: 29789805 PMC: 5896307. DOI: 10.1155/2018/8985718.

References

Shen B, Sibley L . Toxoplasma aldolase is required for metabolism but dispensable for host-cell invasion. Proc Natl Acad Sci U S A. 2014; 111(9):3567-72. PMC: 3948255. DOI: 10.1073/pnas.1315156111. View

Waller R, Ralph S, Reed M, Su V, Douglas J, Minnikin D . A type II pathway for fatty acid biosynthesis presents drug targets in Plasmodium falciparum. Antimicrob Agents Chemother. 2002; 47(1):297-301. PMC: 148988. DOI: 10.1128/AAC.47.1.297-301.2003. View

Olafsson P, Matile H, Certa U . Molecular analysis of Plasmodium falciparum hexokinase. Mol Biochem Parasitol. 1992; 56(1):89-101. DOI: 10.1016/0166-6851(92)90157-f. View

Van Riel N . Dynamic modelling and analysis of biochemical networks: mechanism-based models and model-based experiments. Brief Bioinform. 2006; 7(4):364-74. DOI: 10.1093/bib/bbl040. View

ALBERTY R . Calculation of biochemical net reactions and pathways by using matrix operations. Biophys J. 1996; 71(1):507-15. PMC: 1233501. DOI: 10.1016/S0006-3495(96)79252-4. View

Wiechert W . Modeling and simulation: tools for metabolic engineering. J Biotechnol. 2002; 94(1):37-63. DOI: 10.1016/s0168-1656(01)00418-7. View

Mehta M, Sonawat H, Sharma S . Glycolysis in Plasmodium falciparum results in modulation of host enzyme activities. J Vector Borne Dis. 2006; 43(3):95-103. View

Jain P, Chakma B, Patra S, Goswami P . Potential biomarkers and their applications for rapid and reliable detection of malaria. Biomed Res Int. 2014; 2014:852645. PMC: 3996934. DOI: 10.1155/2014/852645. View

Alam A, Neyaz M, Ikramul Hasan S . Exploiting unique structural and functional properties of malarial glycolytic enzymes for antimalarial drug development. Malar Res Treat. 2015; 2014:451065. PMC: 4280493. DOI: 10.1155/2014/451065. View

10.

Meng T, Somani S, Dhar P . Modeling and simulation of biological systems with stochasticity. In Silico Biol. 2005; 4(3):293-309. View

11.

de Jong H . Modeling and simulation of genetic regulatory systems: a literature review. J Comput Biol. 2002; 9(1):67-103. DOI: 10.1089/10665270252833208. View

12.

Romano A, Conway T . Evolution of carbohydrate metabolic pathways. Res Microbiol. 1996; 147(6-7):448-55. DOI: 10.1016/0923-2508(96)83998-2. View

13.

Lacroix V, Cottret L, Thebault P, Sagot M . An introduction to metabolic networks and their structural analysis. IEEE/ACM Trans Comput Biol Bioinform. 2008; 5(4):594-617. DOI: 10.1109/TCBB.2008.79. View

14.

Mandel J, Palfreyman N, Lopez J, Dubitzky W . Representing bioinformatics causality. Brief Bioinform. 2004; 5(3):270-83. DOI: 10.1093/bib/5.3.270. View

15.

Roth Jr E, Raventos-Suarez C, Perkins M, Nagel R . Glutathione stability and oxidative stress in P. falciparum infection in vitro: responses of normal and G6PD deficient cells. Biochem Biophys Res Commun. 1982; 109(2):355-62. DOI: 10.1016/0006-291x(82)91728-4. View

16.

Reddy V, Mavrovouniotis M, Liebman M . Petri net representations in metabolic pathways. Proc Int Conf Intell Syst Mol Biol. 1993; 1:328-36. View

17.

MacRae J, Dixon M, Dearnley M, Chua H, Chambers J, Kenny S . Mitochondrial metabolism of sexual and asexual blood stages of the malaria parasite Plasmodium falciparum. BMC Biol. 2013; 11:67. PMC: 3704724. DOI: 10.1186/1741-7007-11-67. View

18.

Deville Y, Gilbert D, van Helden J, Wodak S . An overview of data models for the analysis of biochemical pathways. Brief Bioinform. 2003; 4(3):246-59. DOI: 10.1093/bib/4.3.246. View

19.

Koch I, Junker B, Heiner M . Application of Petri net theory for modelling and validation of the sucrose breakdown pathway in the potato tuber. Bioinformatics. 2004; 21(7):1219-26. DOI: 10.1093/bioinformatics/bti145. View

20.

Velanker S, Ray S, Gokhale R, Suma S, Balaram H, Balaram P . Triosephosphate isomerase from Plasmodium falciparum: the crystal structure provides insights into antimalarial drug design. Structure. 1997; 5(6):751-61. DOI: 10.1016/s0969-2126(97)00230-x. View