Contribution in an anthology

Appeared in: Apicomplexan parasites : molecular approaches toward targeted drug development

Editor list: Becker Katja

Publication year: 2011

Pages: 77-96

ISBN: 978-3-527-32731-7

eISBN: 978-3-527-63388-3

DOI Link: https://doi.org/10.1002/9783527633883.ch5

Title of series: Drug discovery in infectious diseases

Number in series: 2

Abstract: 

Malaria is a leading cause of mortality and morbidity globally, accounting for 250 million cases with almost one million deaths per year, mainly in young children. The causative agent of malaria in humans, Plasmodium falciparum, undergoes a complex life cycle, both in the human host and in the Anopheles mosquito vector. In the human host, the merozoite life stage of P. falciparum is responsible for the characteristic symptoms. This life stage requires glycolysis for its energy generation; indeed, selective inhibitors of P. falciparum glycolytic enzymes have been shown to halt proliferation of the parasite. The inhibition of lactate dehydrogenase by gossypol derivatives, as well as by azole-based compounds, also exhibits antimalarial activity. In agreement with these observations, human pyruvate kinase deficiency exerts a protective effect against malaria infection and replication. This phenomenon is comparable to glucose 6-phosphate dehydrogenase deficiency, and indicates that an inhibition of the glycolytic pathway of the host–parasite cell unit is a valuable target for antimalarial strategies. Several enzymes of the glycolytic pathway that convert glucose to lactate have been extensively studied in the context of structure-based inhibitor design. This chapter summarizes the current knowledge of the function, structure, and regulation of important glycolytic enzymes of P. falciparum in comparison to their human counterparts, and elucidates their potential as drug targets.

Harvard Citation style: Jortzig, E. and Becker, K. (2011) Energy metabolism as an antimalarial drug target, in Becker Katja (ed.) Apicomplexan parasites : molecular approaches toward targeted drug development. Weinheim: Wiley-Blackwell, pp. 77-96. https://doi.org/10.1002/9783527633883.ch5

APA Citation style: Jortzig, E., & Becker, K. (2011). Energy metabolism as an antimalarial drug target. In Becker Katja (Ed.), Apicomplexan parasites : molecular approaches toward targeted drug development (pp. 77-96). Wiley-Blackwell. https://doi.org/10.1002/9783527633883.ch5