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Antiprotozoal Agents

Antiprotozoal Agents

Leishmaniasis is a widespread parasitic disease caused by several Leishmania species. It affects millions of people each year and remains a major public health problem in endemic regions. First-line treatment relies on pentavalent antimonials, including meglumine antimoniate and sodium stibogluconate. Even so, how these drugs work has not been fully clear, especially their interaction with parasite-specific biochemical pathways. One key target is trypanothione reductase (TR), an enzyme that...

Leishmaniasis

Leishmaniasis

Leishmaniasis is a protozoal disease caused by species of the genus Leishmania and transmitted through the bite of infected female sandflies. The parasite exists in two principal morphological forms during its life cycle. A sandfly acquires intracellular amastigotes from an infected reservoir host, such as a dog. Within the sandfly, these forms differentiate into motile, flagellated promastigotes. During a subsequent blood meal, promastigotes are injected into the human host, where they...

Amino Acid Biosynthetic Pathways

Amino Acid Biosynthetic Pathways

Amino acid biosynthesis is essential for cell growth, protein synthesis, and metabolic regulation. Cells generate essential and non-essential amino acids from metabolic intermediates to sustain vital biological functions. These intermediates originate from key metabolic pathways: glycolysis, the tricarboxylic acid (TCA) cycle, and the pentose phosphate pathway. Important precursors include α-ketoglutarate, pyruvate, oxaloacetate, phosphoenolpyruvate, and erythrose-4-phosphate, which provide...

Malaria

Malaria

Malaria pathogenesis in humans reflects a delicate interplay between parasite biology and host response. Clinical illness reflects a host’s immune response to the parasite’s asexual replication cycle, which is often asymptomatic in individuals with partial immunity. From the parasite's perspective, transmission between mosquito and human with minimal host pathology is evolutionarily advantageous. Among the six Plasmodium species infecting humans, P. falciparum and P. vivax dominate in global...

Other Glycolytic Pathways

Other Glycolytic Pathways

The pentose phosphate pathway (PPP) operates in parallel with glycolysis, facilitating the metabolism of both pentoses and glucose. This pathway consists of two distinct phases: the oxidative and non-oxidative phases. While it does not directly generate ATP, the intermediates formed during the process can integrate into glycolysis, contributing to cellular energy metabolism when required.Oxidative Phase: NADPH ProductionThe oxidative phase of the pentose phosphate pathway is primarily...

Biosynthesis of Nucleic Acids

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Nucleic acid biosynthesis is a fundamental biochemical process that produces the purine and pyrimidine nucleotides essential for DNA and RNA synthesis. This pathway maintains a balanced nucleotide pool, preventing imbalances that could jeopardize genetic integrity and cellular function. Given the crucial role of nucleotides, their synthesis is tightly regulated to ensure proper cellular homeostasis.Purine BiosynthesisThe biosynthesis of purine nucleotides begins with ribose-5-phosphate, a...

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Related Experiment Video

Updated: May 28, 2026

Quantification of Intracellular Growth Inside Macrophages is a Fast and Reliable Method for Assessing the Virulence of Leishmania Parasites

Quantification of Intracellular Growth Inside Macrophages is a Fast and Reliable Method for Assessing the Virulence of Leishmania Parasites

Published on: March 16, 2018

Folate metabolic pathways in Leishmania.

Tim J Vickers¹, Stephen M Beverley

¹Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA.

Essays in Biochemistry

|October 26, 2011

Summary

Leishmania parasites rely on host folates and pteridines, utilizing unique enzymes like PTR1 that bypass drug targets. This folate pathway offers promising avenues for developing new anti-Leishmania therapies.

Area of Science:

Parasitology
Biochemistry
Drug Discovery

Background:

Leishmania parasites are protozoan pathogens requiring folate and pteridine metabolites.
They possess unique metabolic pathways, including bifunctional dihydrofolate reductase-thymidylate synthase (DHFR-TS) and pteridine reductase 1 (PTR1).
PTR1 can circumvent DHFR inhibition, impacting antifolate drug efficacy.

Purpose of the Study:

To elucidate the folate and pteridine metabolism in Leishmania.
To identify potential drug targets within these pathways.
To explore the repurposing of existing drugs for leishmaniasis treatment.

Main Methods:

Analysis of Leishmania folate and pteridine salvage pathways.
Investigation of enzyme functions, including DHFR-TS and PTR1.

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Quantification of Intracellular Growth Inside Macrophages is a Fast and Reliable Method for Assessing the Virulence of Leishmania Parasites

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Investigating the Phagocytosis of Leishmania using Confocal Microscopy

Investigating the Phagocytosis of Leishmania using Confocal Microscopy

Published on: July 29, 2021

Genetic studies to assess the essentiality of specific metabolic enzymes.

Main Results:

Leishmania salvage essential folates and pteridines from hosts.
PTR1 acts as a bypass mechanism against DHFR inhibitors.
Certain folate pathway enzymes are dispensable, while others impact virulence.
Loss of DHFR-TS can induce protective immunity.

Conclusions:

Leishmania folate metabolism presents multiple targets for chemotherapy.
Existing antifolate drugs may have limited efficacy due to PTR1.
Repurposing drugs for cancer or other infections shows potential for leishmaniasis treatment.