scholarly journals Two independent routes of de novo vitamin B6 biosynthesis: not that different after all

2007 ◽  
Vol 407 (1) ◽  
pp. 1-13 ◽  
Author(s):  
Teresa B. Fitzpatrick ◽  
Nikolaus Amrhein ◽  
Barbara Kappes ◽  
Peter Macheroux ◽  
Ivo Tews ◽  
...  
Keyword(s):  
Vitamin B6 ◽  
De Novo ◽  
Alternative Pathway ◽  
Active Form ◽  
Pentose Phosphate ◽  
Concerted Action ◽  
Human Diet ◽  
Essential Nutrient ◽  
Made In ◽  
Do So

Vitamin B6 is well known in its biochemically active form as pyridoxal 5′-phosphate, an essential cofactor of numerous metabolic enzymes. The vitamin is also implicated in numerous human body functions ranging from modulation of hormone function to its recent discovery as a potent antioxidant. Its de novo biosynthesis occurs only in bacteria, fungi and plants, making it an essential nutrient in the human diet. Despite its paramount importance, its biosynthesis was predominantly investigated in Escherichia coli, where it is synthesized from the condensation of deoxyxylulose 5-phosphate and 4-phosphohydroxy-L-threonine catalysed by the concerted action of PdxA and PdxJ. However, it has now become clear that the majority of organisms capable of producing this vitamin do so via a different route, involving precursors from glycolysis and the pentose phosphate pathway. This alternative pathway is characterized by the presence of two genes, Pdx1 and Pdx2. Their discovery has sparked renewed interest in vitamin B6, and numerous studies have been conducted over the last few years to characterize the new biosynthesis pathway. Indeed, enormous progress has been made in defining the nature of the enzymes involved in both pathways, and important insights have been provided into their mechanisms of action. In the present review, we summarize the recent advances in our knowledge of the biosynthesis of this versatile molecule and compare the two independent routes to the biosynthesis of vitamin B6. Surprisingly, this comparison reveals that the key biosynthetic enzymes of both pathways are, in fact, very similar both structurally and mechanistically.

Structural insights into the catalytic mechanism of the yeast pyridoxal 5-phosphate synthase Snz1

2010 ◽  
Vol 432 (3) ◽  
pp. 445-454 ◽  
Author(s):  
Xuan Zhang ◽  
Yan-Bin Teng ◽  
Jian-Ping Liu ◽  
Yong-Xing He ◽  
Kang Zhou ◽  
...  
Keyword(s):  
Binding Site ◽  
Vitamin B6 ◽  
Active Sites ◽  
Biochemical Analysis ◽  
Catalytic Mechanism ◽  
De Novo ◽  
Active Form ◽  
Dihydroxyacetone Phosphate ◽  
Final Destination ◽  
Structural Insights

In most eubacteria, fungi, apicomplexa, plants and some metazoans, the active form of vitamin B6, PLP (pyridoxal 5-phosphate), is de novo synthesized from three substrates, R5P (ribose 5-phosphate), DHAP (dihydroxyacetone phosphate) and ammonia hydrolysed from glutamine by a complexed glutaminase. Of the three active sites of DXP (deoxyxylulose 5-phosphate)independent PLP synthase (Pdx1), the R5P isomerization site has been assigned, but the sites for DHAP isomerization and PLP formation remain unknown. In the present study, we present the crystal structures of yeast Pdx1/Snz1, in apo-, G3P (glyceraldehyde 3-phosphate)- and PLP-bound forms, at 2.3, 1.8 and 2.2 Å (1 Å=0.1 nm) respectively. Structural and biochemical analysis enabled us to assign the PLP-formation site, a G3P-binding site and a G3P-transfer site. We propose a putative catalytic mechanism for Pdx1/Snz1 in which R5P and DHAP are isomerized at two distinct sites and transferred along well-defined routes to a final destination for PLP synthesis.

scholarly journals Vitamin B6-Dependent Enzymes in the Human Malaria ParasitePlasmodium falciparum: A Druggable Target?

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Thales Kronenberger ◽  
Jasmin Lindner ◽  
Kamila A. Meissner ◽  
Flávia M. Zimbres ◽  
Monika A. Coronado ◽  
...  
Keyword(s):  
Vitamin B6 ◽  
Drug Targets ◽  
Malaria Parasite ◽  
De Novo ◽  
Protein Biosynthesis ◽  
Active Form ◽  
Serine Hydroxymethyltransferase ◽  
Effective Vaccine ◽  
Tropical Regions ◽  
Key Enzyme

Malaria is a deadly infectious disease which affects millions of people each year in tropical regions. There is no effective vaccine available and the treatment is based on drugs which are currently facing an emergence of drug resistance and in this sense the search for new drug targets is indispensable. It is well established that vitamin biosynthetic pathways, such as the vitamin B6de novosynthesis present inPlasmodium, are excellent drug targets. The active form of vitamin B6, pyridoxal 5-phosphate, is, besides its antioxidative properties, a cofactor for a variety of essential enzymes present in the malaria parasite which includes the ornithine decarboxylase (ODC, synthesis of polyamines), the aspartate aminotransferase (AspAT, involved in the protein biosynthesis), and the serine hydroxymethyltransferase (SHMT, a key enzyme within the folate metabolism).

The antioxidative effect of de novo generated vitamin B6 in Plasmodium falciparum validated by protein interference

2012 ◽  
Vol 443 (2) ◽  
pp. 397-405 ◽  
Author(s):  
Julia Knöckel ◽  
Ingrid B. Müller ◽  
Sabine Butzloff ◽  
Bärbel Bergmann ◽  
Rolf D. Walter ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Vitamin B6 ◽  
De Novo ◽  
Active Form ◽  
Cellular Level ◽  
Dominant Negative ◽  
Dominant Negative Effect ◽  
Transcription Analysis

The malaria parasite Plasmodium falciparum is able to synthesize de novo PLP (pyridoxal 5′-phosphate), the active form of vitamin B6. In the present study, we have shown that the de novo synthesized PLP is used by the parasite to detoxify 1O2 (singlet molecular oxygen), a highly destructive reactive oxygen species arising from haemoglobin digestion. The formation of 1O2 and the response of the parasite were monitored by live-cell fluorescence microscopy, by transcription analysis and by determination of PLP levels in the parasite. Pull-down experiments of transgenic parasites overexpressing the vitamin B6-biosynthetic enzymes PfPdx1 and PfPdx2 clearly demonstrated an interaction of the two proteins in vivo which results in an elevated PLP level from 12.5 μM in wild-type parasites to 36.6 μM in the PfPdx1/PfPdx2-overexpressing cells and thus to a higher tolerance towards 1O2. In contrast, by applying the dominant-negative effect on the cellular level using inactive mutants of PfPdx1 and PfPdx2, P. falciparum becomes susceptible to 1O2. Our results demonstrate clearly the crucial role of vitamin B6 biosynthesis in the detoxification of 1O2 in P. falciparum. Besides the known role of PLP as a cofactor of many essential enzymes, this second important task of the vitamin B6de novo synthesis as antioxidant emphasizes the high potential of this pathway as a target of new anti-malarial drugs.

Big Questions in Ecology and Evolution

2009 ◽  
Author(s):  
Thomas N. Sherratt ◽  
David M. Wilkinson
Keyword(s):  
Partial Solution ◽  
Fundamental Importance ◽  
Evolutionary Perspective ◽  
Text Book ◽  
Broad Audience ◽  
The Future ◽  
The Tropics ◽  
Made In ◽  
Do So

Why do we age? Why cooperate? Why do so many species engage in sex? Why do the tropics have so many species? When did humans start to affect world climate? This book provides an introduction to a range of fundamental questions that have taxed evolutionary biologists and ecologists for decades. Some of the phenomena discussed are, on first reflection, simply puzzling to understand from an evolutionary perspective, whilst others have direct implications for the future of the planet. All of the questions posed have at least a partial solution, all have seen exciting breakthroughs in recent years, yet many of the explanations continue to be hotly debated. Big Questions in Ecology and Evolution is a curiosity-driven book, written in an accessible way so as to appeal to a broad audience. It is very deliberately not a formal text book, but something designed to transmit the excitement and breadth of the field by discussing a number of major questions in ecology and evolution and how they have been answered. This is a book aimed at informing and inspiring anybody with an interest in ecology and evolution. It reveals to the reader the immense scope of the field, its fundamental importance, and the exciting breakthroughs that have been made in recent years.

scholarly journals Genome-Wide Metabolic Reconstruction of the Synthesis of Polyhydroxyalkanoates from Sugars and Fatty Acids by Burkholderia Sensu Lato Species

2021 ◽  
Vol 9 (6) ◽  
pp. 1290
Author(s):  
Natalia Alvarez-Santullano ◽  
Pamela Villegas ◽  
Mario Sepúlveda Mardones ◽  
Roberto E. Durán ◽  
Raúl Donoso ◽  
...  
Keyword(s):  
Fatty Acids ◽  
De Novo ◽  
Reducing Power ◽  
Pentose Phosphate ◽  
Fine Tuning ◽  
Metabolic Reconstruction ◽  
Phylogenetic Groups ◽  
Outlier Group ◽  
Pha Genes ◽  
High Level

Burkholderia sensu lato (s.l.) species have a versatile metabolism. The aims of this review are the genomic reconstruction of the metabolic pathways involved in the synthesis of polyhydroxyalkanoates (PHAs) by Burkholderia s.l. genera, and the characterization of the PHA synthases and the pha genes organization. The reports of the PHA synthesis from different substrates by Burkholderia s.l. strains were reviewed. Genome-guided metabolic reconstruction involving the conversion of sugars and fatty acids into PHAs by 37 Burkholderia s.l. species was performed. Sugars are metabolized via the Entner–Doudoroff (ED), pentose-phosphate (PP), and lower Embden–Meyerhoff–Parnas (EMP) pathways, which produce reducing power through NAD(P)H synthesis and PHA precursors. Fatty acid substrates are metabolized via β-oxidation and de novo synthesis of fatty acids into PHAs. The analysis of 194 Burkholderia s.l. genomes revealed that all strains have the phaC, phaA, and phaB genes for PHA synthesis, wherein the phaC gene is generally present in ≥2 copies. PHA synthases were classified into four phylogenetic groups belonging to class I II and III PHA synthases and one outlier group. The reconstruction of PHAs synthesis revealed a high level of gene redundancy probably reflecting complex regulatory layers that provide fine tuning according to diverse substrates and physiological conditions.

Quel corpus pour l’étude du dialecte niçois ?

2021 ◽  
Vol 137 (2) ◽  
pp. 344-361
Author(s):  
Philippe Del Giudice
Keyword(s):  
Middle Ages ◽  
Written Language ◽  
Linguistic Features ◽  
Descriptive Grammar ◽  
Written Production ◽  
Starting Point ◽  
Social Use ◽  
Over Time ◽  
Made In ◽  
Do So

Abstract A new project has just been launched to write a synchronic, descriptive grammar of Niçois, the Occitan dialect of Nice. In this article, I define the corpus of the research. To do so, I first review written production from the Middle Ages to the present. I then analyze the linguistic features of Niçois over time, in order to determine the precise starting point of the current language state. But because of reinforced normativism and the decreasing social use of Niçois among the educated population, written language after WWII became artificial and does not really correspond to recordings made in the field. The corpus will thus be composed of writings from the 1820’s to WWII and recordings from the last few decades.

scholarly journals Revealing the Metabolic Alterations during Biofilm Development of Burkholderia cenocepacia Based on Genome-Scale Metabolic Modeling

Metabolites ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 221
Author(s):  
Ozlem Altay ◽  
Cheng Zhang ◽  
Hasan Turkez ◽  
Jens Nielsen ◽  
Mathias Uhlén ◽  
...  
Keyword(s):  
Systems Biology ◽  
Alternative Pathway ◽  
Growth Conditions ◽  
Pentose Phosphate ◽  
Burkholderia Cenocepacia ◽  
Bacterial Cells ◽  
Metabolic Remodeling ◽  
Transcriptomics Data ◽  
Biofilm Development ◽  
Genome Scale

Burkholderia cenocepacia is among the important pathogens isolated from cystic fibrosis (CF) patients. It has attracted considerable attention because of its capacity to evade host immune defenses during chronic infection. Advances in systems biology methodologies have led to the emergence of methods that integrate experimental transcriptomics data and genome-scale metabolic models (GEMs). Here, we integrated transcriptomics data of bacterial cells grown on exponential and biofilm conditions into a manually curated GEM of B. cenocepacia. We observed substantial differences in pathway response to different growth conditions and alternative pathway susceptibility to extracellular nutrient availability. For instance, we found that blockage of the reactions was vital through the lipid biosynthesis pathways in the exponential phase and the absence of microenvironmental lysine and tryptophan are essential for survival. During biofilm development, bacteria mostly had conserved lipid metabolism but altered pathway activities associated with several amino acids and pentose phosphate pathways. Furthermore, conversion of serine to pyruvate and 2,5-dioxopentanoate synthesis are also identified as potential targets for metabolic remodeling during biofilm development. Altogether, our integrative systems biology analysis revealed the interactions between the bacteria and its microenvironment and enabled the discovery of antimicrobial targets for biofilm-related diseases.

scholarly journals The 1930s Horror Adventure Film on Location in Jamaica: ‘Jungle Gods’, ‘Voodoo Drums’ and ‘Mumbo Jumbo’ in the ‘Secret Places of Paradise Island’

Humanities ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 62
Author(s):  
Emiel Martens
Keyword(s):  
American Literature ◽  
American Empire ◽  
Sound Film ◽  
Mumbo Jumbo ◽  
First Sound ◽  
African Caribbean ◽  
The Caribbean ◽  
Black Populations ◽  
Made In ◽  
Do So

In this article, I consider the representation of African-Caribbean religions in the early horror adventure film from a postcolonial perspective. I do so by zooming in on Ouanga (1935), Obeah (1935), and Devil’s Daughter (1939), three low-budget horror productions filmed on location in Jamaica during the 1930s (and the only films shot on the island throughout that decade). First, I discuss the emergence of depictions of African-Caribbean religious practices of voodoo and obeah in popular Euro-American literature, and show how the zombie figure entered Euro-American empire cinema in the 1930s as a colonial expression of tropical savagery and jungle terror. Then, combining historical newspaper research with content analyses of these films, I present my exploration into the three low-budget horror films in two parts. The first part contains a discussion of Ouanga, the first sound film ever made in Jamaica and allegedly the first zombie film ever shot on location in the Caribbean. In this early horror adventure, which was made in the final year of the U.S. occupation of Haiti, zombies were portrayed as products of evil supernatural powers to be oppressed by colonial rule. In the second part, I review Obeah and The Devil’s Daughter, two horror adventure movies that merely portrayed African-Caribbean religion as primitive superstition. While Obeah was disturbingly set on a tropical island in the South Seas infested by voodoo practices and native cannibals, The Devil’s Daughter was authorized by the British Board of Censors to show black populations in Jamaica and elsewhere in the colonial world that African-Caribbean religions were both fraudulent and dangerous. Taking into account both the production and content of these movies, I show that these 1930s horror adventure films shot on location in Jamaica were rooted in a long colonial tradition of demonizing and terrorizing African-Caribbean religions—a tradition that lasts until today.

scholarly journals De Novo Atypical Haemolytic Uremic Syndrome after Kidney Transplantation

2018 ◽  
Vol 2018 ◽  
pp. 1-4
Author(s):  
Arnaud Devresse ◽  
Martine de Meyer ◽  
Selda Aydin ◽  
Karin Dahan ◽  
Nada Kanaan
Keyword(s):  
Kidney Transplantation ◽  
De Novo ◽  
Alternative Pathway ◽  
Factor H ◽  
Complement Factor ◽  
Haemolytic Uremic Syndrome ◽  
Hinman Syndrome ◽  
Uremic Syndrome ◽  
Stage Renal Disease ◽  
End Stage

De novo thrombotic microangiopathy (TMA) can occur after kidney transplantation. An abnormality of the alternative pathway of complement must be suspected and searched for, even in presence of a secondary cause. We report the case of a 23-year-old female patient who was transplanted with a kidney from her mother for end-stage renal disease secondary to Hinman syndrome. Early after transplantation, she presented with 2 episodes of severe pyelonephritis, associated with acute kidney dysfunction and biological and histological features of TMA. Investigations of the alternative pathway of the complement system revealed atypical haemolytic uremic syndrome secondary to complement factor I mutation, associated with mutations in CD46 and complement factor H related protein genes. Plasma exchanges followed by eculizumab injections allowed improvement of kidney function without, however, normalization of creatinine.

scholarly journals Atheists

2017 ◽  
Author(s):  
Sarah R. Schiavone ◽  
Will M Gervais
Keyword(s):  
Cognitive Processes ◽  
Scientific Progress ◽  
Psychological Research ◽  
Cultural Learning ◽  
Negative Attitudes ◽  
Complex Interactions ◽  
Cultural Origins ◽  
Made In ◽  
Do So

Atheists represent an inconspicuous minority, identifiable only by their disbelief in God(s). Despite being highly stigmatized and disliked, until recent scientific endeavors, little has been known about this group including why they don’t believe, how many people are atheists, and why they trigger intense reactions. Thus, this paper aims to synthesize what is known about atheists (so far), and to help explain the widespread negative attitudes and prejudice towards atheists; the possible cognitive, motivational, and cultural origins of disbelief; and the unique challenges facing the study of religious disbelievers. To do so, we will explore current findings in psychological research on atheism by considering the complex interactions of cultural learning, motivations, and core cognitive processes. Although significant scientific progress has been made in understanding the factors underlying atheism, there remains much to be explored in the domain of religious disbelief.

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