Related Experiment Video
Updated: May 26, 2026
14:26
Purification of Extracellular Trypanosomes, Including African, from Blood by Anion-Exchangers (Diethylaminoethyl-cellulose Columns)
Published on: April 6, 2019
Regulation and function of polyamines in African trypanosomes
Erin Willert1, Margaret A Phillips
1Department of Pharmacology, University of Texas Southwestern Medical Center at Dallas, 6001 Forest Park Road, Dallas, TX 75390-9041, USA.
Trends in Parasitology
|December 24, 2011
Summary
The polyamine pathway is crucial for treating human African trypanosomiasis (HAT). In Trypanosoma brucei, the enzyme S-adenosylmethionine decarboxylase (AdoMetDC) activity is regulated by prozyme protein levels, not typical cellular mechanisms.
Area of Science:
- Biochemistry
- Parasitology
- Drug Discovery
Background:
- The polyamine biosynthetic pathway is a key drug target for treating human African trypanosomiasis (HAT).
- Unlike mammalian cells, trypanosomes lack apparent tight control mechanisms for polyamine levels.
- S-adenosylmethionine decarboxylase (AdoMetDC) catalyzes spermidine biosynthesis, a critical step in polyamine production.
Purpose of the Study:
- To investigate the regulation of polyamine biosynthesis in trypanosomes.
- To understand the role of prozyme in the activation of AdoMetDC.
- To explore potential drug targets for HAT treatment.
Main Methods:
- Comparative analysis of polyamine regulation in mammalian cells versus trypanosomes.
- Enzyme kinetics studies of AdoMetDC and its interaction with prozyme.
- Investigation of gene duplication events leading to prozyme evolution.
Main Results:
- Trypanosomatid AdoMetDC requires dimerization with prozyme for activation.
- Prozyme is an inactive paralog of AdoMetDC, unique to trypanosomatids.
- AdoMetDC activity in Trypanosoma brucei is primarily controlled by regulating prozyme protein levels.
Conclusions:
- Polyamine regulation in trypanosomes differs significantly from mammalian systems.
- Prozyme plays a critical role in controlling spermidine biosynthesis in trypanosomes.
- Targeting the prozyme-AdoMetDC interaction could be a viable strategy for HAT drug development.
More Related Videos
Related Concept Videos
01:26Physical Properties of Amines
Amines with low molecular weight are usually gaseous at room temperature, while those with high molecular weight are liquid or solids in nature. Usually, low molecular weight amines have a rotten fish-like smell. Diamines typically have a pungent smell. For instance, cadaverine and putrescine, depicted in Figure 1, are two molecules responsible for decaying tissue.
01:15Anthelminthic Agents
Anthelmintic drugs differ significantly from antiparasitic therapies targeting protozoa, primarily due to differences in parasite biology. Whereas most protozoal treatments act on proliferating cells, anthelmintics are typically directed against mature, nonproliferative helminths. The therapeutic approach considers the helminth's reliance on neuromuscular coordination, glucose metabolism, and microtubular integrity for survival, reproduction, and localization within the host. Most anthelmintics...
01:02Phosphorylation
The addition or removal of phosphate groups from proteins is the most common chemical modification that regulates cellular processes. These modifications can affect the structure, activity, stability, and localization of proteins within cells as well as their interactions with other proteins.
During phosphorylation, protein kinases transfer the terminal phosphate group of ATP to specific amino acid side chains of substrate proteins. Serine, threonine, and tyrosine are the most commonly...
During phosphorylation, protein kinases transfer the terminal phosphate group of ATP to specific amino acid side chains of substrate proteins. Serine, threonine, and tyrosine are the most commonly...
01:19Allosteric Proteins-ATCase
Binding sites linkages can regulate a protein's function. For example, enzyme activity is often regulated through a feedback mechanism where the end product of the biochemical process serves as an inhibitor.
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis pathway,...
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis pathway,...
01:28Biosynthesis of Nucleic Acids
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...
02:54Protein Kinases and Phosphatases
Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...