4.12.3.10 Reduced pyrimidines (metabolic intermediates) and their nucleosides

Author(s):  
D. Shugar ◽  
A. Psoda

2013 ◽  
Vol 83 (3) ◽  
pp. 188-197 ◽  
Author(s):  
Rebecca L. Sweet ◽  
Jason A. Zastre

It is well established that thiamine deficiency results in an excess of metabolic intermediates such as lactate and pyruvate, which is likely due to insufficient levels of cofactor for the function of thiamine-dependent enzymes. When in excess, both pyruvate and lactate can increase the stabilization of the hypoxia-inducible factor 1-alpha (HIF-1α) transcription factor, resulting in the trans-activation of HIF-1α regulated genes independent of low oxygen, termed pseudo-hypoxia. Therefore, the resulting dysfunction in cellular metabolism and accumulation of pyruvate and lactate during thiamine deficiency may facilitate a pseudo-hypoxic state. In order to investigate the possibility of a transcriptional relationship between hypoxia and thiamine deficiency, we measured alterations in metabolic intermediates, HIF-1α stabilization, and gene expression. We found an increase in intracellular pyruvate and extracellular lactate levels after thiamine deficiency exposure to the neuroblastoma cell line SK-N-BE. Similar to cells exposed to hypoxia, there was a corresponding increase in HIF-1α stabilization and activation of target gene expression during thiamine deficiency, including glucose transporter-1 (GLUT1), vascular endothelial growth factor (VEGF), and aldolase A. Both hypoxia and thiamine deficiency exposure resulted in an increase in the expression of the thiamine transporter SLC19A3. These results indicate thiamine deficiency induces HIF-1α-mediated gene expression similar to that observed in hypoxic stress, and may provide evidence for a central transcriptional response associated with the clinical manifestations of thiamine deficiency.



Foods ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1734
Author(s):  
Ana Mencher ◽  
Pilar Morales ◽  
Jordi Tronchoni ◽  
Ramon Gonzalez

In parallel with the development of non-Saccharomyces starter cultures in oenology, a growing interest has developed around the interactions between the microorganisms involved in the transformation of grape must into wine. Nowadays, it is widely accepted that the outcome of a fermentation process involving two or more inoculated yeast species will be different from the weighted average of the corresponding individual cultures. Interspecific interactions between wine yeasts take place on several levels, including interference competition, exploitation competition, exchange of metabolic intermediates, and others. Some interactions could be a simple consequence of each yeast running its own metabolic programme in a context where metabolic intermediates and end products from other yeasts are present. However, there are clear indications, in some cases, of specific recognition between interacting yeasts. In this article we discuss the mechanisms that may be involved in the communication between wine yeasts during alcoholic fermentation.



2013 ◽  
Vol 288 (49) ◽  
pp. 35322-35332 ◽  
Author(s):  
Ana Casañal ◽  
Ulrich Zander ◽  
Cristina Muñoz ◽  
Florine Dupeux ◽  
Irene Luque ◽  
...  


Transfusion ◽  
1979 ◽  
Vol 19 (4) ◽  
pp. 467-471 ◽  
Author(s):  
E Beutler ◽  
W Kuhl ◽  
C Tegos


Nature ◽  
1968 ◽  
Vol 217 (5131) ◽  
pp. 847-848 ◽  
Author(s):  
G. A. O. ALLEYNE


2021 ◽  
Vol 22 (11) ◽  
pp. 5597
Author(s):  
Vítězslav Plocek ◽  
Kristýna Fadrhonc ◽  
Jana Maršíková ◽  
Libuše Váchová ◽  
Alexandra Pokorná ◽  
...  

During development of yeast colonies, various cell subpopulations form, which differ in their properties and specifically localize within the structure. Three branches of mitochondrial retrograde (RTG) signaling play a role in colony development and differentiation, each of them activating the production of specific markers in different cell types. Here, aiming to identify proteins and processes controlled by the RTG pathway, we analyzed proteomes of individual cell subpopulations from colonies of strains, mutated in genes of the RTG pathway. Resulting data, along with microscopic analyses revealed that the RTG pathway predominantly regulates processes in U cells, long-lived cells with unique properties, which are localized in upper colony regions. Rtg proteins therein activate processes leading to amino acid biosynthesis, including transport of metabolic intermediates between compartments, but also repress expression of mitochondrial ribosome components, thus possibly contributing to reduced mitochondrial translation in U cells. The results reveal the RTG pathway’s role in activating metabolic processes, important in U cell adaptation to altered nutritional conditions. They also point to the important role of Rtg regulators in repressing mitochondrial activity in U cells.





Author(s):  
Peng Xu

AbstractMicrobial consortium is a complex adaptive system with higher order dynamic characteristics that are not present by individual members. To accurately predict the social interactions, we formulate a set of unstructured kinetic models to quantitatively capture the dynamic interactions of multiple microbial species. By introducing an interaction coefficient, we analytically derived the steady state solutions for the interacting species and the substrate profile in the chemostat. We analyzed the stability of the possible co-existing states defined by competition, parasitism, amensalism, commensalism and cooperation. Our model predicts that only parasitism, commensalism and cooperation could lead to stable co-existing state. We also determined the optimal social interaction criteria of microbial coculture with sequential metabolic reactions compartmentalized into two distinct species. Coupled with Luedeking–Piret and Michaelis-Menten equations, accumulation of metabolic intermediates in one species and formation of end-product in another species could be derived and assessed. We discovered that parasitism consortia disfavor the bioconversion of intermediate to final product; and commensalism consortia could efficiently convert metabolic intermediates to final product and maintain metabolic homeostasis with a broad range of operational conditions (i.e., dilution rates); whereas cooperative consortia leads to highly nonlinear pattern of precursor accumulation and end-product formation. The underlying dynamics and emergent properties of microbial consortia may provide critical knowledge for us to engineer efficient bioconversion process, deliver effective gut therapeutics as well as elucidate probiotic-pathogen interactions in general.



2004 ◽  
Vol 186 (14) ◽  
pp. 4528-4534 ◽  
Author(s):  
Nicola Zamboni ◽  
Eliane Fischer ◽  
Dietmar Laudert ◽  
Stéphane Aymerich ◽  
Hans-Peter Hohmann ◽  
...  

ABSTRACT Despite the importance of the oxidative pentose phosphate (PP) pathway as a major source of reducing power and metabolic intermediates for biosynthetic processes, almost no direct genetic or biochemical evidence is available for Bacillus subtilis. Using a combination of knockout mutations in known and putative genes of the oxidative PP pathway and 13C-labeling experiments, we demonstrated that yqjI encodes the NADP+-dependent 6-P-gluconate dehydrogenase, as was hypothesized previously from sequence similarities. Moreover, YqjI was the predominant isoenzyme during glucose and gluconate catabolism, and its role in the oxidative PP pathway could not be played by either of two homologues, GntZ and YqeC. This conclusion is in contrast to the generally held view that GntZ is the relevant isoform; hence, we propose a new designation for yqjI, gndA, the monocistronic gene encoding the principal 6-P-gluconate dehydrogenase. Although we demonstrated the NAD+-dependent 6-P-gluconate dehydrogenase activity of GntZ, gntZ mutants exhibited no detectable phenotype on glucose, and GntZ did not contribute to PP pathway fluxes during growth on glucose. Since gntZ mutants grew normally on gluconate, the functional role of GntZ remains obscure, as does the role of the third homologue, YqeC. Knockout of the glucose-6-P dehydrogenase-encoding zwf gene was primarily compensated for by increased glycolytic fluxes, but about 5% of the catabolic flux was rerouted through the gluconate bypass with glucose dehydrogenase as the key enzyme.



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