scholarly journals Metabolic dependency of chorismate in Plasmodium falciparum

2019 ◽  
Author(s):  
Ana Lisa Valenciano ◽  
Maria L. Fernández-Murga ◽  
Emilio F. Merino ◽  
Nicole R. Holderman ◽  
Grant J. Butschek ◽  
...  

The shikimate pathway, a metabolic pathway absent in humans, is responsible for the production of chorismate, a branch point metabolite. In the malaria parasite, chorismate is postulated to be a direct precursor in the synthesis of p-aminobenzoic acid (folate biosynthesis), p-hydroxybenzoic acid (ubiquinone biosynthesis), menaquinone, and aromatic amino acids. While the potential value of the shikimate pathway as a drug target is debatable, the metabolic dependency of chorismate in P. falciparum remains unclear. Current evidence suggests that the main role of chorismate is folate biosynthesis despite ubiquinone biosynthesis being active and essential in the malaria parasite. Our goal in the present work was to expand our knowledge of the ubiquinone head group biosynthesis and its potential metabolic dependency on chorismate in P. falciparum. These data led us to further characterize the mechanism of action of MMV688345, a compound from the open-access “Pathogen Box” collection from Medicine for Malaria Venture. We systematically assessed the development of both asexual and sexual stages of P. falciparum in a defined medium in the absence of an exogenous supply of chorismate end-products and present biochemical evidence suggesting that the benzoquinone ring of ubiquinones in this parasite may be synthesized through a yet unidentified route.

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Ana Lisa Valenciano ◽  
Maria L. Fernández-Murga ◽  
Emilio F. Merino ◽  
Nicole R. Holderman ◽  
Grant J. Butschek ◽  
...  

Abstract The shikimate pathway, a metabolic pathway absent in humans, is responsible for the production of chorismate, a branch point metabolite. In the malaria parasite, chorismate is postulated to be a direct precursor in the synthesis of p-aminobenzoic acid (folate biosynthesis), p-hydroxybenzoic acid (ubiquinone biosynthesis), menaquinone, and aromatic amino acids. While the potential value of the shikimate pathway as a drug target is debatable, the metabolic dependency of chorismate in P. falciparum remains unclear. Current evidence suggests that the main role of chorismate is folate biosynthesis despite ubiquinone biosynthesis being active and essential in the malaria parasite. Our goal in the present work was to expand our knowledge of the ubiquinone head group biosynthesis and its potential metabolic dependency on chorismate in P. falciparum. We systematically assessed the development of both asexual and sexual stages of P. falciparum in a defined medium in the absence of an exogenous supply of chorismate end-products and present biochemical evidence suggesting that the benzoquinone ring of ubiquinones in this parasite may be synthesized through a yet unidentified route.


2019 ◽  
Vol 1 (1) ◽  
pp. 11-18
Author(s):  
Siti Nur Purwandhani

Folate, an important B-group vitamin, participates in many metabolic pathways such as DNA and RNA biosynthesis and amino acid inter-conversions. Mammalian cells cannot synthesize folate; therefore, an exogenous supply of this vitamin is necessary to prevent nutritional deficiency. Folic acid is a composite molecule, being made up of three parts: a pteridine ring system (6-methylpterin), para-aminobenzoic acid , and glutamic acid . The folate biosynthesis pathway in micro-organisms can be divided in several parts. The pteridine proportion of folate is made from GTP, that is synthesized in the purine biosynthesis pathway. p-Aminobenzoic acid originates from chorismate and can be synthesized via the same biosynthesis pathways required for the aromatic amino acids, involving glycolysis, pentose phosphate pathway and shikimate pathway. The third component of a folate molecule is glutamate, that is normally taken up from the medium. This review will focus on biosynthesis and folate production by lactic acid bacteria and the folate level production in fermented product.


2010 ◽  
Vol 100 (3) ◽  
pp. 262-270 ◽  
Author(s):  
Giuliano Degrassi ◽  
Giulia Devescovi ◽  
Joseph Bigirimana ◽  
Vittorio Venturi

Chorismate mutase (CM) is a key enzyme in the shikimate pathway which is responsible for the synthesis of aromatic amino acids. There are two classes of CMs, AroQ and AroH, and several pathogenic bacteria have been reported to possess a subgroup of CMs designated AroQγ. These CMs are usually exported to the periplasm or outside the cell; in a few cases, they have been reported to be involved in virulence and their precise role is currently unknown. Here, we report that the important rice pathogen Xanthomonas oryzae pv. oryzae XKK.12 produces an AroQγ CM which we have purified and characterized from spent supernatants. This enzyme is synthesized in planta and X. oryzae pv. oryzae knock-out mutants are hypervirulent to rice. The role of this enzyme in X. oryzae pv. oryzae rice virulence is discussed.


2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Juana P Sanchez-Villamil ◽  
Veronica D’Annunzio ◽  
Ines Rebagliati ◽  
Paola Finocchietto ◽  
Jorge Peralta ◽  
...  

Introduction: Current evidence suggests a main role of thioredoxin-1 (trx1) in the protection against oxidative stress. However, it is unknown yet a putative role of trx1 in the regulation of contractility and mitochondrial function, dynamics and biogenesis in sepsis-induced myocardial dysfunction in which oxidative stress is an underlying cause. Methods: Transgenic male mice (Tg-trx1) and its wildtype (wt) were subjected to cecal ligation and double puncture or sham operation. After 6, 18 and 24 h, antioxidant enzymes, protein carbonylation and mitocondrial function were evaluated. Hearts were isolated and perfused using the Langendorff technique. Inotropism was evaluated through left ventricular developed pressure (LVDP) and contractile reserve after β-adrenergic stimulus by addition of isoproterenol (ISO) (1 μM). Evaluation of mitochondrial fusion-fission dynamics (Drp1, Mfn2, Opa1) and biogenesis (PGC-1α, NRF-1 and TFAM) were made by real-time qPCR. Results: Over the time course of sepsis, there was an improvement in average life expectancy in Tg-trx1 (Tg-trx1: 36, wt: 28 h; p=0.0204), and 15 percentages points higher β -adrenergic response at 6 h compared to wt (22.8 vs 7.8%, means of relative percentage differences respectively). Inhibition of complex I activity, protein oxidation, and loss of membrane potential was lower in Tg-trx1, with a sustained MnSOD activity at 24 h. mRNA levels of Opa1 were significantly reduced in sepsis, accompanied by ultrastructural alterations in mitochondrial cristae, while significant Drp1 activation (measured by Ser P616 phosphorylation) was observed in wt mice at 24 h. PGC-1 α mRNA decreased at 6 h in both groups, and then, showed a 2.5-fold increase in Tg-trx1 at 24 h. Autophagy was demonstrated by increased LC3-II/LC3-I ratios in both groups during the progression of sepsis, although the levels were early higher in Tg-Trx1. No indicators of apoptosis were observed. Conclusions: The results show that mice with cardiac-specific overexpression of Trx1 have higher survival. Trx1 provides protection against oxidative stress, which seems to preserve contractile reserve and keep mitochondrial biogenesis. Associated with mitochondrial autophagy-processes allow mitochondrial renewal and life extension.


Biology ◽  
2022 ◽  
Vol 11 (1) ◽  
pp. 86
Author(s):  
Songwei Wang ◽  
Dongliang Liu ◽  
Muhammad Bilal ◽  
Wei Wang ◽  
Xuehong Zhang

DAHP synthase catalyzes the first step in the shikimate pathway, deriving the biosynthesis of aromatic amino acids (Trp, Phe and Tyr), phenazine-1-carboxamide, folic acid, and ubiquinone in Pseudomonas chlororaphis. In this study, we identified and characterized one DAHP synthase encoding gene phzC, which differs from the reported DAHP synthase encoding genes aroF, aroG and aroH in E. coli. PhzC accounts for approximately 90% of the total DAHP synthase activities in P. chlororaphis HT66 and plays the most critical role in four DAHP synthases in the shikimate pathway. Inactivation of phzC resulted in the reduction of PCN production by more than 90%, while the absence of genes aroF, aroG and aroH reduced PCN yield by less than 15%, and the production of PCN was restored after the complementation of gene phzC. Moreover, the results showed that phzC in P. chlororaphis HT66 is not sensitive to feedback inhibition. This study demonstrated that gene phzC is essential for PCN biosynthesis. The expression level of both phzC and phzE genes are not inhibited in feedback by PCN production due to the absence of a loop region required for allosteric control reaction. This study highlighted the importance of PhzC and applying P. chlororaphis for shikimate pathway-derived high-value biological production.


Author(s):  
Hideo Hayashi ◽  
Yoshikazu Hirai ◽  
John T. Penniston

Spectrin is a membrane associated protein most of which properties have been tentatively elucidated. A main role of the protein has been assumed to give a supporting structure to inside of the membrane. As reported previously, however, the isolated spectrin molecule underwent self assemble to form such as fibrous, meshwork, dispersed or aggregated arrangements depending upon the buffer suspended and was suggested to play an active role in the membrane conformational changes. In this study, the role of spectrin and actin was examined in terms of the molecular arrangements on the erythrocyte membrane surface with correlation to the functional states of the ghosts.Human erythrocyte ghosts were prepared from either freshly drawn or stocked bank blood by the method of Dodge et al with a slight modification as described before. Anti-spectrin antibody was raised against rabbit by injection of purified spectrin and partially purified.


2020 ◽  
Vol 48 (2) ◽  
pp. 429-439 ◽  
Author(s):  
Jorge Gago ◽  
Danilo M. Daloso ◽  
Marc Carriquí ◽  
Miquel Nadal ◽  
Melanie Morales ◽  
...  

Besides stomata, the photosynthetic CO2 pathway also involves the transport of CO2 from the sub-stomatal air spaces inside to the carboxylation sites in the chloroplast stroma, where Rubisco is located. This pathway is far to be a simple and direct way, formed by series of consecutive barriers that the CO2 should cross to be finally assimilated in photosynthesis, known as the mesophyll conductance (gm). Therefore, the gm reflects the pathway through different air, water and biophysical barriers within the leaf tissues and cell structures. Currently, it is known that gm can impose the same level of limitation (or even higher depending of the conditions) to photosynthesis than the wider known stomata or biochemistry. In this mini-review, we are focused on each of the gm determinants to summarize the current knowledge on the mechanisms driving gm from anatomical to metabolic and biochemical perspectives. Special attention deserve the latest studies demonstrating the importance of the molecular mechanisms driving anatomical traits as cell wall and the chloroplast surface exposed to the mesophyll airspaces (Sc/S) that significantly constrain gm. However, even considering these recent discoveries, still is poorly understood the mechanisms about signaling pathways linking the environment a/biotic stressors with gm responses. Thus, considering the main role of gm as a major driver of the CO2 availability at the carboxylation sites, future studies into these aspects will help us to understand photosynthesis responses in a global change framework.


2018 ◽  
Vol 5 (1) ◽  
pp. 93-115
Author(s):  
Miloš Stamenković

SummarySports photography undoubtedly has a significant place in sports press and publicism. It’s main and primary role is to present sports to the readers as art, which it is. Sport is characterized by dynamic and varied movements, and the main role of sports photography is reflected in the fact that it is in this way that sport shows its essence. Having in mind that photography tells more than a thousand words it sends a clear message to the reader as well to people who are informed about events via sports portals. Sports photography is a multidimensional art for many reasons. When we say “multi”, it primarily refers to a wider range that sports photography has to offer, which means sports photography is not only directed at presenting athletes on the move and the main actors who contribute to achieving the results by their engagement – it also has the role of sports “psychophotography” which is an analysis and capture of the emotional reaction of an athlete after winning or losing from the opposing team.


2020 ◽  
Vol 26 (6) ◽  
pp. 1283-1296
Author(s):  
K.A. Omarieva ◽  
P.G. Isaeva

Subject. The article addresses problems and prospects for the banking supervision development in the Russian Federation under modern conditions. Objectives. We review the essence and methods of organization of the banking supervision, and identify the main problems and prospects for its development. Methods. To provide valid, reliable and reasoned recommendations, we apply normative and integrated approaches to the study of the banking supervision effectiveness in the current circumstances. Results. The paper investigates main problems and development prospects for the Russian banking supervision. The essential importance of supervision comes from the main role of the banking system in maintaining accounts of economic entities and making settlements. Even minor failures or delays in operations can lead to negative outcomes and disastrous consequences for the entire monetary system and the national economy. Therefore, we highlight issues that require attention, and make proposals for further development of the banking supervision. Conclusions. In the context of dynamically developing economy, the banking practice is becoming more complex. As a result, there is a need for new financial instruments that can reduce risks, increase the speed and efficiency of operations and document flow, and help achieve the world levels of introduced standards.


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