259 research outputs found
Molecular mechanisms of nucleoside recycling in the brain
No full textA major role of plasma membrane bound ectonucleotidases is the modulation of ATP, ADP, adenosine (the purinergic agonists), UTP, and UDP (the pyrimidinergic agonists) availability in the extracellular space at their respective receptors. We have recently shown that an ATP driven uridine-UTP cycle is operative in the brain, based on the strictly compartmentalized processes of uridine salvage to UTP and uridine generation from UTP, in which uptaken uridine is anabolized to UTP in the cytosol, and converted back to uridine in the extracellular space by the action of ectonucleotidases (Ipata et al. Int J Biochem Cell Biol 2010;42:932-7). In this paper we show that a similar cytidine-CTP cycle exists in rat brain. Since (i) brain relies on imported preformed nucleosides for the synthesis of nucleotides, RNA, nuclear and mitochondrial DNA, coenzymes, pyrimidine sugar- and lipid-conjugates and (ii) no specific pyrimidinergic receptors have been identified for cytidine and their nucleotides, our results, taken together with previous studies on the intra- and extracellular metabolic network of ATP, GTP, UTP, and their nucleosides in the brain (Barsotti and Ipata. Int J Biochem Cell Biol 2004;36:2214-25; Balestri et al. Neurochem Int 2007;50:517-23), strongly suggest that, apart from the modulation of ligand availability, ectonucleotidases may serve the process of local nucleoside recycling in the brain
Glycogen as a fuel:metabolic interaction between glycogen and ATP catabolism in oxygen-independent muscle contraction
No full textThe functional logic of 5'nucleotidases
No full textAdenosine- and uridine-cytidine kinases, purine-nucleoside phosphorylase, hypoxanthine-guanine phosphoribosyl transferase, and several related enzymes, are components of the salvage pathways which reduce the loss of intracellular purine and pyrimidine rings. Although this could explain the role of these enzymes, it poses a problem of the role of the cytosolic 5'-nucleotidase. Why are nucleosides produced from nucleoside-monophosphates, only to be converted back to the same compounds? To date, it is well established that a cross talk exists between the extracellular and intracellular nucleoside metabolism. In districts, such as brain, which are dependent on salvage nucleotide synthesis, nucleosides are produced through the action of the ecto-5'-nucleotidase, the last component of a series of plasma-membrane bound enzyme proteins, catalyzing the successive dephosphorylation of released nucleoside-triphosphates. Both nucleosidetriphosphates (mainly ATP and UTP) and nucleosides (mainly adenosine), act as extracellular signals. Once transported into cell cytosol, all nucleosides are salvaged back to nucleoside-triphosphates, with the exception of inosine, whose salvage is limited to IMP. Intracellular balance of nucleosides is maintained by the action of several enzymes, such as adenosine deaminase, uridine phosphorylase and cytidine deaminase, and by at least three 5'-nucleotidases, the ADP activated AMP preferring cN-IA, the ATP-ADP activated IMP-GMP preferring cN-II, and the UMP-CMP preferring cN-III. Here we are reviewing the mechanisms whereby cytosolic 5'-nucleotidases control changes in nucleoside and nucleotide concentration, with the aim to provide a common basis for the study of the relationship between biochemistry and other related disciplines, such as physiology and pharmacology
The Regulation of Brain Nucleoside Utilization
No full textThe homeostatic regulation of intracellular purine and pyrimidine pools has long been studied at the level of de novo nucleotide synthesis. However, brain maintains the proper qualitative and quantitative nucleotide balance by salvaging preformed nucleosides, imported from blood stream, rather than by de novo synthesis from simple precursors. The main salvage enzymes are the nucleoside-kinases, catalyzing the ATP mediated phosphorylation of nucleosides in their 5’-position. Salvaged nucleoside-monophosphates are then either further phosphorylated, or converted back to nucleosides by a set of 5’-nucleotidases. This poses the following problem: why are nucleosides produced from nucleosidemonophosphates, to be converted back to the same compounds at the expense of ATP? As discussed in this article, the quantitative and qualitative intracellular balance of brain purine and pyrimidine compounds is maintained i) by the intracellular interplay between the rates of nucleoside-kinases and 5’-nucleotidases, ii) by the relative rates of the inward and outward nucleoside transport through equilibrative and concentrative transport systems, iii) by the metabolic cross-talk between extracellularly exported nucleoside-triphosphate breakdown and the intracellular process of nucleoside-triphosphate salvage synthesis
Spatial variation in Posidonia oceanica structural, morphological and dynamic features in a northwestern Mediterranean coastal area: a multi-scale analysis
No full textKnowledge of the natural pattern of spatial variation of the variables of interest is fundamental for designing effective sampling strategies to be used in surveys and monitoring programs. Unfortunately, little is known on patterns of spatial variation of structural, morphological and dynamic features of Posidonia oceanica, despite their increasing use as indicators of the status and/or trend of meadows. Here, variations in some such features (such as shoot density, leaf biometry, annual rhizome elongation and leaf formation) were examined on a hierarchy of spatial scales, ranging from cm within individual meadows, to meadows separated by 10 km, using independent full-nested analyses of variance. Overall, at least 3 variables showed significant variations in the mean values on each of the scales examined. Patterns of variability differed among individual traits. Most of the total variation, however, was on the smallest spatial scale examined (i.e. among replicates, shoots or quadrats). For some variables, a significant variation was also associated with the largest scale (i.e. among meadows). Collectively, the results indicated that patchiness in density, morphology and growth exists on a very local scale within R oceanica meadows along the same isobath. This suggests that sampling designs and analyses which incorporate different spatial scales and appropriate replications should at least be considered in the future when planning large-scale and long-term surveys
Metabolic interaction between urea cycle and cytric acid cycle shunt. A guided approach
No full textThis article is a guided pedagogical approach, devoted to
postgraduate students specializing in biochemistry, aimed at
presenting all single reactions and overall equations leading
to the metabolic interaction between ureagenesis and citric
acid cycle to be incorporated into a two-three lecture series
about the interaction of urea cycle with other metabolic pathways.
We emphasize that citrate synthetase, aconitase, and
isocitrate dehydrogenase, three enzymes of the citric acid
cycle are not involved, thus creating a shunt in citric acid
cycle. In contrast, the glutamic-oxaloacetate transaminase,
which does not belong to citric acid cycle, has a paramount
importance in the metabolic interaction of the two cycles,
because it generates aspartate, one of the two fuel molecules
of urea cycle, and a-ketoglutarate, an intermediate of
the citric acid cycle. Finally, students should appreciate that
balancing equations for all atoms and charges is not only a
stoichiometric task, but strongly facilitates the discussion of
the physiological roles of metabolic pathways. Indeed, this
exercise has been used in the classroom, to encourage a
deeper level of understanding of an important biochemical
issue. VC 2017 by The International Union of Biochemistry
and Molecular Biology, 00:000–000, 2017
Survival and growth of transplanted and natural seedlings of Posidonia oceanica (L.) Delile in a damaged coastal area
No full textGender and content bias in Large Language Models: a case study on Google Gemini 2.0 Flash Experimental
No full textThis study evaluates the biases in Gemini 2.0 Flash Experimental, a state-of-the-art large language model (LLM) developed by Google, focusing on content moderation and gender disparities. By comparing its performance to ChatGPT-4o, examined in a previous work of the author, the analysis highlights some differences in ethical moderation practices. Gemini 2.0 demonstrates reduced
gender bias, notably with female-specific prompts achieving a substantial rise in acceptance rates compared to results obtained by ChatGPT-4o. It adopts a more permissive stance toward sexual content and maintains relatively high acceptance rates for violent prompts (including gender-specific cases). Despite these changes, whether they constitute an improvement is debatable. While gender bias has been reduced, this reduction comes at the cost of permitting more violent content toward both males and females, potentially normalizing violence rather than mitigating harm. Male-specific prompts still generally receive higher acceptance rates than female-specific ones. These findings
underscore the complexities of aligning AI systems with ethical standards, highlighting progress in reducing certain biases while raising concerns about the broader implications of the model’s permissiveness. Ongoing refinements are essential to achieve moderation practices that ensure transparency, fairness, and inclusivity without amplifying harmful content
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