Publications by authors named "Juan L Concepcion"

In Leishmania, the nucleotide-sugar UDP-galactose can be synthesized by a salvage pathway, the Isselbacher route, involving phosphorylation of galactose and the action of UDP-sugar pyrophosphorylase. The first enzyme of the pathway, galactokinase, has yet to be studied in this parasite. Here, we report a molecular and biochemical characterization of this enzyme in Leishmania mexicana.

View Article and Find Full Text PDF
Article Synopsis
  • Per-ARNT-Sim (PAS) domains are found in many organisms and are crucial for regulating enzymatic activity and environmental adaptation by binding small ligands.
  • Researchers characterized a specific phosphoglycerate kinase with a PAS domain (TcPAS-PGK) from the parasite Trypanosoma cruzi, identifying it as an active enzyme localized in glycosomes.
  • The study compares the substrate affinities of two protein forms—one with the PAS domain and one without—finding differences in their activity patterns and inhibition at high substrate concentrations.
View Article and Find Full Text PDF
Article Synopsis
  • The study shows that epimastigotes grown in galactose-supplemented LIT medium have improved viability under stress compared to those grown in glucose.
  • Results indicate that galactose enhances cellular responses to oxidative agents like hydrogen peroxide and methylene blue.
  • The research also highlights the location of phosphoglucomutase activity in the cytosol and differences in hexose phosphate release from glycosomes depending on the sugar source.
View Article and Find Full Text PDF
Article Synopsis
  • Arginine kinase (AK) is an enzyme linked to allergic reactions in invertebrates and is also present in the parasite T. cruzi, which causes Chagas disease.
  • The study investigated the presence of specific antibodies against T. cruzi AK (TcAK) in patients with chronic Chagas disease (CCD) and found differing levels of IgG and IgE antibodies between infected and non-infected individuals.
  • Results suggest that TcAK might play a role in influencing B cell responses and could contribute to allergic reactions during T. cruzi infection, revealing a potential new target for understanding immune responses in affected patients.
View Article and Find Full Text PDF
Article Synopsis
  • Phosphoglycerate kinase (PGK) is a key glycolytic enzyme involved in ATP production and gluconeogenesis, functioning primarily as a monomeric enzyme of about 45 kDa.
  • PGK is recognized as a moonlighting protein, meaning it has additional roles beyond energy metabolism, including participation in disease pathogenesis, nucleic acid interactions, and tumor progression.
  • Analysis of different kinetoplastid organisms reveals multiple PGK isoforms, some of which are unusually large and may be catalytically inactive, raising questions about the significance of PGK gene duplication and its implications for kinetoplastid parasites.
View Article and Find Full Text PDF

Trypanosoma cruzi, the causative agent of Chagas' disease, belongs to the Trypanosomatidae family. The parasite undergoes multiple morphological and metabolic changes during its life cycle, in which it can use both glucose and amino acids as carbon and energy sources. The glycolytic pathway is peculiar in that its first six or seven steps are compartmentalized in glycosomes, and has a two-branched auxiliary glycosomal system functioning beyond the intermediate phosphoenolpyruvate (PEP) that is also used in the cytosol as substrate by pyruvate kinase.

View Article and Find Full Text PDF
Article Synopsis
  • Glycosomes in Trypanosoma cruzi, which cause Chagas disease, are specialized peroxisomes that compartmentalize the first seven steps of glycolysis and other metabolic processes.
  • The study involved purifying glycosomes from the T. cruzi epimastigotes, collecting soluble and membrane fractions, and using NaCO treatment and osmotic shock to separate the proteins.
  • Proteomic analysis confirmed known enzymes in these metabolic pathways and revealed new components present in the glycosomes of the parasite.
View Article and Find Full Text PDF
Article Synopsis
  • PAS domains are crucial protein modules involved in cellular signaling and regulation across a variety of organisms, functioning as sensors for different stimuli.
  • These domains enable proteins to respond to a range of signals, including light, oxygen, and metabolic changes, influencing critical processes like development and gene regulation.
  • Research indicates that kinetoplastid species, particularly Trypanosoma cruzi, possess unique PAS-containing kinases that have large open-reading frames and unusual domain combinations not commonly found in other eukaryotes.
View Article and Find Full Text PDF
Article Synopsis
  • The study investigated the prevalence of Trypanosoma cruzi infection in Sucre State, Venezuela, using cluster sampling across 96 villages and 576 homes, analyzing 2,212 serum samples.
  • The seroprevalence found was 3.12%, with various risk factors identified, including poor housing conditions and the presence of accumulated garbage and certain types of roofing and flooring.
  • Individual age also played a role, with seropositive cases found even in children under 15, indicating that Sucre State has significant risk factors for T. cruzi infection.
View Article and Find Full Text PDF
Article Synopsis
  • Trypanosoma rangeli is a protist that infects various mammals and humans in Central and South America, but does not cause disease in humans; it is studied for its similarities to Trypanosoma cruzi, the cause of Chagas' disease.
  • Research on T. rangeli reveals that its glycolytic enzymes, responsible for breaking down glucose, are primarily contained within glycosomes for the initial steps, while the final steps occur in the cytosol, differing from T. cruzi.
  • T. rangeli shows unique metabolic characteristics, such as not excreting ammonium and being dependent on glucose for survival, highlighting its different metabolic behavior compared to similar organisms.
View Article and Find Full Text PDF
Article Synopsis
  • Designed a reporter system to be used on ELISA plates that utilizes the rK346 protein from Leishmania infantum, which is specific and highly antigenic.
  • The rK346 protein was coupled with horseradish peroxidase C (HRPc) through two different methods: glutaraldehyde and sulfo-SMCC, each yielding a diverse range of molecular weights and conjugation stoichiometries.
  • The sulfo-SMCC method showed improved efficiency in conjugation compared to glutaraldehyde, making it a promising option for developing a cost-effective and specific reporter system to detect visceral leishmaniasis in individuals at various risk stages.
View Article and Find Full Text PDF

Trypanosoma evansi is a widely-distributed haemoflagellated parasite of veterinary importance that infects a variety of mammals including horses, mules, camels, buffalos, cattle and deer. It is the causal agent of a trypanosomiasis known as Surra which produces epidemics of great economic importance in Africa, Asia and South America. The main pathology includes an enlarged spleen with hypertrophy of lymphoid follicles, congested lungs, neuronal degeneration and meningoencephalitis, where migration of the parasites from the blood to the tissues is essential.

View Article and Find Full Text PDF
Article Synopsis
  • Researchers cloned and sequenced two galactokinase genes (TcGALK-1 and TcGALK-2) from Trypanosoma cruzi, producing an active and soluble enzyme from TcGALK-1 and a less soluble enzyme from TcGALK-2 when expressed in E. coli.
  • The study found different Km values for galactose and ATP for both proteins, with substrate inhibition by ATP noted in TcGALK-2, while confirming their presence in glycosomes.
  • Phylogenetic analysis showed that T. cruzi galactokinases are closely related to those from Leishmania spp. and emphasized their potential role in utilizing galactose as a carbon source in glucose-depleted environments.
View Article and Find Full Text PDF

The remodelling of organelle function is increasingly appreciated as a central driver of eukaryotic biodiversity and evolution. Kinetoplastids including Trypanosoma and Leishmania have evolved specialized peroxisomes, called glycosomes. Glycosomes uniquely contain a glycolytic pathway as well as other enzymes, which underpin the physiological flexibility of these major human pathogens.

View Article and Find Full Text PDF

Trypanosoma cruzi, like other trypanosomatids analyzed so far, can use both glucose and amino acids as carbon and energy source. In these parasites, glycolysis is compartmentalized in glycosomes, authentic but specialized peroxisomes. The major part of this pathway, as well as a two-branched glycolytic auxiliary system, are present in these organelles.

View Article and Find Full Text PDF
Article Synopsis
  • Trypanosoma evansi is a protist that infects horses and other economically important animals, relying on glycolysis for energy like its relative, T. brucei.
  • In T. evansi, enzymes associated with glycolysis are located in specialized organelles called glycosomes, which are similar to peroxisomes.
  • The discovery of two additional enzymes, phosphoenolpyruvate carboxykinase and PPi-dependent pyruvate phosphate dikinase, in T. evansi's glycosomes alters previously held assumptions about how this parasite metabolizes glucose for energy.
View Article and Find Full Text PDF

American Trypanosomiasis (Chagas disease) is an infectious disease caused by the hemoflagellate parasite Trypanosoma cruzi which is transmitted by reduviid bugs. T. cruzi infection occurs in a broad spectrum of reservoir animals throughout North, Central, and South America and usually evolves into an asymptomatic chronic clinical stage of the disease in which diagnosis is often challenging.

View Article and Find Full Text PDF

Leishmaniasis is an infectious disease caused by protozoan parasites of the genus Leishmania which are transmitted to humans through bites of infected sand flies. The variable clinical manifestations and the evolution of the disease are determined by the infecting species. Recognition at a species level is of utmost importance since this greatly impacts therapy decision making as well as predicts outcome for the disease.

View Article and Find Full Text PDF

Chagas disease is a public health problem worldwide. The availability of diagnostic tools to predict the development of chronic Chagas cardiomyopathy is crucial to reduce morbidity and mortality. Here we analyze the prognostic value of adenosine deaminase serum activity (ADA) and C-reactive protein serum levels (CRP) in chagasic individuals.

View Article and Find Full Text PDF
Article Synopsis
  • The ecological niche of Reduvidae vectors has changed due to environmental shifts and human activity in rural areas.
  • This study examines triatomine bugs that carry Trypanosoma cruzi in Sucre State, Venezuela, using a survey of 95 towns and 577 homes.
  • Despite a low vector infection rate of 1.72%, high household colonization (33.33%) indicates potential continued transmission of the disease.
View Article and Find Full Text PDF
Article Synopsis
  • Three isoenzymes of phosphoglycerate kinase (PGK) exist in Trypanosoma cruzi: PGKB (cytosolic), and PGKA/PGKC (glycosomal).
  • PGKA is linked to the glycosomal membrane and accounts for about 23% of glycosomal PGK activity, while PGKC accounts for the remaining 77%.
  • Blocking PGKA with specific antibodies significantly reduces glucose consumption in epimastigotes, highlighting its key role in supporting glycolysis in these parasites.
View Article and Find Full Text PDF

In Trypanosoma cruzi, the causal agent of Chagas disease, the first six or seven steps of glycolysis are compartmentalized in glycosomes, which are authentic but specialized peroxisomes. Hexokinase (HK), the first enzyme in the glycolytic pathway, has been an important research object, particularly as a potential drug target. Here we present the results of a specific kinetics study of the native HK from T.

View Article and Find Full Text PDF

Rationale: Chagas cardiomyopathy, caused by the protozoan Trypanosoma cruzi, is characterized by alterations in intracellular ion, heart failure and arrhythmias. Arrhythmias have been related to sudden death, even in asymptomatic patients, and their molecular mechanisms have not been fully elucidated.

Objective: The aim of this study is to demonstrate the effect of proteins secreted by T.

View Article and Find Full Text PDF
Article Synopsis
  • Glycosomal membrane proteins in Leishmania mexicana are essential for coordinating metabolic activities between the cytosol and glycosomes.
  • An inventory revealed that 70% of proteins were found in a hydrophobic fraction, indicating a strong association with membranes, while 20% were soluble after treatment with Na2CO3.
  • The study identified 14 key polypeptides, primarily integral proteins, with the 50 kDa protein being the most prevalent, and major phospholipids in the membranes included phosphatidyl-ethanolamine and phosphatidyl-choline, suggesting a role in sterol biosynthesis.
View Article and Find Full Text PDF

This study evaluates the risk factors associated with the diagnosis of chronic chagasic miocardiopathy (CChM) in 115 seropositive individuals to anti-Trypanosoma cruzi antibodies, in Barinas state, Venezuela. Serology was performed with ELISA and MABA; while the CChM diagnosis was established by electrocardiography and echocardiography. A complete clinical history including epidemiological, personal/familiar antecedents and psychobiological habits, plus socioeconomic, psychosocial and alimentary habits interviews were performed for each individual.

View Article and Find Full Text PDF