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2.
Materials (Basel) ; 14(1)2020 Dec 31.
Article in English | MEDLINE | ID: mdl-33396469

ABSTRACT

The unique properties that nanoparticles exhibit, due to their small size, are the principal reason for their numerous applications, but at the same time, this might be a massive menace to the environment. The number of studies that assess the possible ecotoxicity of nanomaterials has been increasing over the last decade to determine if, despite the positive aspects, they should be considered a potential health risk. To evaluate their potential toxicity, models are used in all types of organisms, from unicellular bacteria to complex animal species. In order to better understand the environmental consequences of nanotechnology, this literature review aims to describe and classify nanoparticles, evaluating their life cycle, their environmental releasing capacity and the type of impact, particularly on living beings, highlighting the need to develop more severe and detailed legislation. Due to their diversity, nanoparticles will be discussed in generic terms focusing on the impact of a great variety of them, highlighting the most interesting ones for the industry.

3.
J Mol Biol ; 431(5): 956-969, 2019 03 01.
Article in English | MEDLINE | ID: mdl-30664871

ABSTRACT

Inosine 5'-monophosphate dehydrogenase (IMPDH) catalyzes the rate-limiting step in the de novo GTP biosynthetic pathway and plays essential roles in cell proliferation. As a clinical target, IMPDH has been studied for decades, but it has only been within the last years that we are starting to understand the complexity of the mechanisms of its physiological regulation. Here, we report structural and functional insights into how adenine and guanine nucleotides control a conformational switch that modulates the assembly of the two human IMPDH enzymes into cytoophidia and allosterically regulates their catalytic activity. In vitro reconstituted micron-length cytoophidia-like structures show catalytic activity comparable to unassembled IMPDH but, in turn, are more resistant to GTP/GDP allosteric inhibition. Therefore, IMPDH cytoophidia formation facilitates the accumulation of high levels of guanine nucleotides when the cell requires it. Finally, we demonstrate that most of the IMPDH retinopathy-associated mutations abrogate GTP/GDP-induced allosteric inhibition and alter cytoophidia dynamics.


Subject(s)
IMP Dehydrogenase/metabolism , Nucleotides/metabolism , Catalysis , Cell Line, Tumor , Cell Proliferation/physiology , Guanosine Triphosphate/metabolism , HeLa Cells , Humans , Molecular Conformation , Polymerization
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