scholarly journals The Uptake and Metabolism of Amino Acids, and Their Unique Role in the Biology of Pathogenic Trypanosomatids

Pathogens ◽  
2018 ◽  
Vol 7 (2) ◽  
pp. 36 ◽  
Author(s):  
Letícia Marchese ◽  
Janaina Nascimento ◽  
Flávia Damasceno ◽  
Frédéric Bringaud ◽  
Paul Michels ◽  
...  
Keyword(s):  
Amino Acids ◽  
Trypanosoma Cruzi ◽  
Trypanosoma Brucei ◽  
Life Cycles ◽  
Unique Role ◽  
Physical Chemical ◽  
Intermediate Metabolites ◽  
Natural Hosts ◽  
Uptake And Metabolism ◽  
Genus Leishmania

Trypanosoma brucei, as well as Trypanosoma cruzi and more than 20 species of the genus Leishmania, form a group of flagellated protists that threaten human health. These organisms are transmitted by insects that, together with mammals, are their natural hosts. This implies that during their life cycles each of them faces environments with different physical, chemical, biochemical, and biological characteristics. In this work we review how amino acids are obtained from such environments, how they are metabolized, and how they and some of their intermediate metabolites are used as a survival toolbox to cope with the different conditions in which these parasites should establish the infections in the insects and mammalian hosts.

scholarly journals Major Surface Protease of Trypanosomatids: One Size Fits All?

2009 ◽  
Vol 78 (1) ◽  
pp. 22-31 ◽  
Author(s):  
Chaoqun Yao
Keyword(s):  
Extracellular Matrix ◽  
Plasma Membrane ◽  
Trypanosoma Cruzi ◽  
Trypanosoma Brucei ◽  
Life Cycles ◽  
Cellular Functions ◽  
Time Points ◽  
Intracellular Amastigotes ◽  
Extracellular Release ◽  
Major Surface

ABSTRACT Major surface protease (MSP or GP63) is the most abundant glycoprotein localized to the plasma membrane of Leishmania promastigotes. MSP plays several important roles in the pathogenesis of leishmaniasis, including but not limited to (i) evasion of complement-mediated lysis, (ii) facilitation of macrophage (Mø) phagocytosis of promastigotes, (iii) interaction with the extracellular matrix, (iv) inhibition of natural killer cellular functions, (v) resistance to antimicrobial peptide killing, (vi) degradation of Mø and fibroblast cytosolic proteins, and (vii) promotion of survival of intracellular amastigotes. MSP homologues have been found in all other trypanosomatids studied to date including heteroxenous members of Trypanosoma cruzi, the extracellular Trypanosoma brucei, unusual intraerythrocytic Endotrypanum spp., phytoparasitic Phytomonas spp., and numerous monoxenous species. These proteins are likely to perform roles different from those described for Leishmania spp. Multiple MSPs in individual cells may play distinct roles at some time points in trypanosomatid life cycles and collaborative or redundant roles at others. The cellular locations and the extracellular release of MSPs are also discussed in connection with MSP functions in leishmanial promastigotes.

scholarly journals Subsite specificity (S3, S2, S1', S2' and S3') of oligopeptidase B from Trypanosoma cruzi and Trypanosoma brucei using fluorescent quenched peptides: comparative study and identification of specific carboxypeptidase activity

2003 ◽  
Vol 373 (3) ◽  
pp. 933-939 ◽  
Author(s):  
Jefferson P. HEMERLY ◽  
Vitor OLIVEIRA ◽  
Elaine DEL NERY ◽  
Rory E. MORTY ◽  
Norma W. ANDREWS ◽  
...  
Keyword(s):  
Amino Acids ◽  
Trypanosoma Cruzi ◽  
Trypanosoma Brucei ◽  
Peptide Bond ◽  
Minimum Size ◽  
Amino Acid Residues ◽  
Basic Amino Acids ◽  
Oligopeptidase B ◽  
Work Supports ◽  
Micromolar Range

We characterized the extended substrate binding site of recombinant oligopeptidase B enzymes from Trypanosoma cruzi (Tc-OP) and Trypanosoma brucei (Tb-OP), evaluating the specificity of their S3, S2, S1′, S2′ and S3′ subsites. Five series of internally quenched fluorescent peptides based on the substrate Abz-AGGRGAQ-EDDnp [where Abz is o-aminobenzoic acid and EDDnp is N-(2,4-dinitrophenyl)ethylenediamine] were designed to contain amino acid residues with side chains of a minimum size, and each residue position of this substrate was modified. Synthetic peptides of different lengths derived from the human kininogen sequence were also examined, and peptides of up to 17 amino acids were found to be hydrolysed by Tc-OP and Tb-OP. These two oligopeptidases were essentially arginyl hydrolases, since for all peptides examined the only cleavage site was the Arg–Xaa bond. We also demonstrated that Tc-OP and Tb-OP have a very specific carboxypeptidase activity for basic amino acids, which depends on the presence of at least of a pair of basic amino acids at the C-terminal end of the substrate. The peptide with triple Arg residues (Abz-AGRRRAQ-EDDnp) was an efficient substrate for Tc-OP and Tb-OP: the Arg–Ala peptide bond was cleaved first and then two C-terminal Arg residues were successively removed. The S1′ subsite seems to be an important determinant of the specificity of both enzymes, showing a preference for Tyr, Ser, Thr and Gln as hydrogen donors. The presence of these amino acids at P1′ resulted in substrates that were hydrolysed with Km values in the sub-micromolar range. Taken together, this work supports the view that oligopeptidase B is a specialized protein-processing enzyme with a specific carboxypeptidase activity. Excellent substrates were obtained for Tb-OP and Tc-OP (Abz-AMRRTISQ-EDDnp and Abz-AHKRYSHQ-EDDnp respectively), which were hydrolysed with remarkably high kcat and low Km values.

scholarly journals Differential Inhibition of Human and Trypanosome Ubiquitin E1S by TAK-243 Offers Possibilities for Parasite Selective Inhibitors

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
D. Roeland Boer ◽  
Marie-José Bijlmakers
Keyword(s):  
Amino Acids ◽  
Trypanosoma Cruzi ◽  
Trypanosoma Brucei ◽  
Human African Trypanosomiasis ◽  
Potent Inhibitor ◽  
Model System ◽  
Differential Inhibition ◽  
Protein Ubiquitination ◽  
Related Compounds

Abstract Novel strategies to target Trypanosoma brucei, Trypanosoma cruzi and Leishmania are urgently needed to generate better and safer drugs against Human African Trypanosomiasis, Chagas disease and Leishmaniasis, respectively. Here, we investigated the feasibility of selectively targeting in trypanosomatids the ubiquitin E1 activating enzyme (UBA1), an essential eukaryotic protein required for protein ubiquitination. Trypanosomatids contain two UBA1 genes in contrast to mammals and yeast that only have one, and using T. brucei as a model system, we show that both are active in vitro. Surprisingly, neither protein is inhibited by TAK-243, a potent inhibitor of human UBA1. This resistance stems from differences with the human protein at key amino acids, which includes a residue termed the gatekeeper because its mutation in E1s leads to resistance to TAK-243 and related compounds. Importantly, our results predict that trypanosomatid selective UBA1 inhibition is feasible and suggest ways to design novel compounds to achieve this.

Basic Biology of Trypanosoma Cruzi

2020 ◽  
Vol 26 ◽  
Author(s):  
Aline Araujo Zuma ◽  
Emile dos Santos Barrias ◽  
Wanderley de Souza
Keyword(s):  
Trypanosoma Cruzi ◽  
Trypanosoma Brucei ◽  
Cell Biology ◽  
Structural Organization ◽  
Developmental Stages ◽  
Endocytic Pathway ◽  
Host Cells ◽  
Cellular Organization ◽  
Basic Biology ◽  
Comparative Information

Abstract:: The present review addresses basic aspects of the biology of the pathogenic protozoa Trypanosoma cruzi and some comparative information with Trypanosoma brucei. Like eukaryotic cells, their cellular organization is similar to that of mammalian hosts. However, these parasites present structural particularities. That is why the following topics are emphasized in this paper: developmental stages of the life cycle in the vertebrate and invertebrate hosts; the cytoskeleton of the protozoa, especially the sub-pellicular microtubules; the flagellum and its attachment to the protozoan body through specialized junctions; the kinetoplast-mitochondrion complex, including its structural organization and DNA replication; the glycosome and its role in the metabolism of the cell; the acidocalcisome, describing its morphology, biochemistry, and functional role; the cytostome and the endocytic pathway; the organization of the endoplasmic reticulum and Golgi complex; the nucleus, describing its structural organization during interphase and division; and the process of interaction of the parasite with host cells. The unique characteristics of these structures also make them interesting chemotherapeutic targets. Therefore, further understanding of cell biology aspects contributes to the development of drugs for chemotherapy.

scholarly journals Foamy Viruses, Bet, and APOBEC3 Restriction

Viruses ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 504
Author(s):  
Ananda Ayyappan Jaguva Vasudevan ◽  
Daniel Becker ◽  
Tom Luedde ◽  
Holger Gohlke ◽  
Carsten Münk
Keyword(s):  
Current Knowledge ◽  
Regulatory Protein ◽  
Host Population ◽  
Life Cycles ◽  
Restriction Factors ◽  
Host Restriction ◽  
Open Questions ◽  
Foamy Viruses ◽  
Natural Hosts ◽  
Hiv 1

Non-human primates (NHP) are an important source of viruses that can spillover to humans and, after adaptation, spread through the host population. Whereas HIV-1 and HTLV-1 emerged as retroviral pathogens in humans, a unique class of retroviruses called foamy viruses (FV) with zoonotic potential are occasionally detected in bushmeat hunters or zookeepers. Various FVs are endemic in numerous mammalian natural hosts, such as primates, felines, bovines, and equines, and other animals, but not in humans. They are apathogenic, and significant differences exist between the viral life cycles of FV and other retroviruses. Importantly, FVs replicate in the presence of many well-defined retroviral restriction factors such as TRIM5α, BST2 (Tetherin), MX2, and APOBEC3 (A3). While the interaction of A3s with HIV-1 is well studied, the escape mechanisms of FVs from restriction by A3 is much less explored. Here we review the current knowledge of FV biology, host restriction factors, and FV–host interactions with an emphasis on the consequences of FV regulatory protein Bet binding to A3s and outline crucial open questions for future studies.

Ileal digestibility of protein and amino acids of feed peas with different trypsin inhibitor activity in pigs

2000 ◽  
Vol 80 (4) ◽  
pp. 643-652 ◽  
Author(s):  
F. Grosjean ◽  
C. Jondreville ◽  
I. Williatte-Hazouard ◽  
F. Skiba ◽  
B. Carrouée ◽  
...  
Keyword(s):  
Amino Acids ◽  
Trypsin Inhibitor ◽  
Crude Protein ◽  
Trypsin Inhibitor Activity ◽  
Rectal Anastomosis ◽  
Inhibitor Activity ◽  
Ileal Digestibility ◽  
Physical Chemical ◽  
Protein Amino Acids ◽  
Weight Proportion

Ileal digestibility of protein and amino acids was measured in pigs fed 13 round, tannin-free peas samples and related to the following physical, chemical and biological characteristics of these samples: thousand-seed weight, proportion of hulls, starch, fibre, crude protein, ether extract and ash contents, trypsin inhibitor activity and trypsin inhibitor activity per unit of crude protein (TIAP). Each pea sample was included in a diet containing starch, sucrose, minerals and vitamins and fed to four barrows (50 to 100 kg) fitted with an end-to-end ileo-rectal anastomosis. Standardised ileal protein and amino acid digestibilities, except for alanine of peas decreased linearly with increasing TIAP (P < 0.01) and was not affected by fiber content. For example standardized ileal digestibilities values (%) decreased by −0.1975, −0.1617, −0.2171, −0.2630, −0.2029 and −0.3536 per unit of TIAP (expressed in unit of trypsin inhibited per milligram crude protein), respectively, for crude protein and lysine, threonine, methionine, cystine and tryptophan. Key words: Peas, trypsin inhibitor activity, standardised ileal digestibilities, protein, amino acids, pig

Origins of Chagas disease: Didelphis species are natural hosts of Trypanosoma cruzi I and armadillos hosts of Trypanosoma cruzi II, including hybrids

2005 ◽  
Vol 35 (2) ◽  
pp. 225-233 ◽  
Author(s):  
Matthew Yeo ◽  
Nidia Acosta ◽  
Martin Llewellyn ◽  
Humberto Sánchez ◽  
Susie Adamson ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Natural Hosts

Uptake and Metabolism of Serotonin and Amino Acids in Thiamine Deficiency

1981 ◽  
pp. 391-416 ◽  
Author(s):  
A. Plaitakis ◽  
W. J. Nicklas ◽  
M. H. Van Woert ◽  
E. Chung Hwang ◽  
S. Berl
Keyword(s):  
Amino Acids ◽  
Thiamine Deficiency ◽  
Uptake And Metabolism

scholarly journals The Complex Compound of Amino Acids With Titanium (III) as a Method to Control and Synthesis of Different Structures of TiO2 Nanoparticles; Usage as Photocatalysts to Oxidize Alcohols to Aldehyde

2021 ◽  
Author(s):  
Yahya Absalan ◽  
Nazanin Noroozi Shad ◽  
Mostafa Gholizadeh
Keyword(s):  
Amino Acids ◽  
Titanium Dioxide ◽  
Uv Light ◽  
Chemical Analyses ◽  
Benzyl Alcohols ◽  
Titanium Dioxide Nanoparticle ◽  
Physical Chemical ◽  
Nitrobenzyl Alcohol ◽  
Different Types ◽  
Full Investigation

Abstract Different types of the amino acids (Glutamine, Glycine, Alanine) were used to coordinate TiCl3 in order to investigating the best precursor for synthesis of TiO2. Also, a full investigation was carried out to synthesis four different structures of TiO2 nanoparticles [TiO2 (A0.8R0.2), TiO2 (A0.6R0.4), TiO2 (Anatase), and TiO2 (Rutile)]. Oxidation of derivatives alcohol to their corresponding aldehyde through the obtained nanoparticles, as a photocatalyst, under UV light was considered to investigate the best structure of TiO2. Different physical-chemical analyses were applied to investigate the result. The result showed that the titanium dioxide nanoparticle, synthesized from glycine was obtained at the least temperature and was chosen as a precursor to synthesis of four different types of TiO2. All the synthesized TiO2 were applied for oxidation of benzyl alcohols into benzaldehyde, as a test, and TiO2 (A0.6R0.4) could give the best result (87% efficiency). Then it was used to oxidize benzyl alcohol, 4-cholorobenzyl alcohol, 4-nitrobenzyl alcohol and 4-methoxybenzyl alcohol to their corresponding aldehyde and efficiency were 74, 92, 87, and 65% respectively.

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