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36 results on '"Allegrini, Simone"'

1. Interplay between mTOR and Purine Metabolism Enzymes and Its Relevant Role in Cancer.

Author

Allegrini, Simone, Camici, Marcella, Garcia-Gil, Mercedes, Pesi, Rossana, and Tozzi, Maria Grazia

Subjects
*ENZYME metabolism, *CELL metabolism, *NUCLEOTIDE synthesis, *PURINE nucleotides, *ANTINEOPLASTIC agents
Abstract

Tumor cells reprogram their metabolism to meet the increased demand for nucleotides and other molecules necessary for growth and proliferation. In fact, cancer cells are characterized by an increased "de novo" synthesis of purine nucleotides. Therefore, it is not surprising that specific enzymes of purine metabolism are the targets of drugs as antineoplastic agents, and a better knowledge of the mechanisms underlying their regulation would be of great help in finding new therapeutic approaches. The mammalian target of the rapamycin (mTOR) signaling pathway, which is often activated in cancer cells, promotes anabolic processes and is a major regulator of cell growth and division. Among the numerous effects exerted by mTOR, noteworthy is its empowerment of the "de novo" synthesis of nucleotides, accomplished by supporting the formation of purinosomes, and by increasing the availability of necessary precursors, such as one-carbon formyl group, bicarbonate and 5-phosphoribosyl-1-pyrophosphate. In this review, we highlight the connection between purine and mitochondrial metabolism, and the bidirectional relation between mTOR signaling and purine synthesis pathways. [ABSTRACT FROM AUTHOR]

Published
2024
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2. Inborn Errors of Purine Salvage and Catabolism

Author

Camici, Marcella, primary, Garcia-Gil, Mercedes, additional, Allegrini, Simone, additional, Pesi, Rossana, additional, Bernardini, Giulia, additional, Micheli, Vanna, additional, and Tozzi, Maria Grazia, additional

Published
2023
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25. Initial Studies to Define the Physiologic Role of cN-II

Author

Filoni, Daniela Nicole, primary, Pesi, Rossana, additional, Careddu, Maria Giovanna, additional, Camici, Marcella, additional, Allegrini, Simone, additional, Collavoli, Anita, additional, Scarfone, Ilaria, additional, Zucchi, Francesca, additional, Galli, Alvaro, additional, and Tozzi, Maria Grazia, additional

Published
2011
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32. Structural basis of the substrate specificity of Bacillus cereus adenosine phosphorylase.

Author

Dessanti, Paola, Zhang, Yang, Allegrini, Simone, Tozzi, Maria Grazia, Sgarrella, Francesco, and Ealick, Steven E.

Subjects
PURINE nucleoside phosphorylase, NUCLEOSIDES, BACILLUS cereus, ADENOSINE monophosphate, ADENOSINES, INOSINE
Abstract

Purine nucleoside phosphorylases catalyze the phosphorolytic cleavage of the glycosidic bond of purine (2′-deoxy)nucleosides, generating the corresponding free base and (2′-deoxy)ribose 1-phosphate. Two classes of PNPs have been identified: homotrimers specific for 6-oxopurines and homohexamers that accept both 6-oxopurines and 6-aminopurines. Bacillus cereus adenosine phosphorylase (AdoP) is a hexameric PNP; however, it is highly specific for 6-aminopurines. To investigate the structural basis for the unique substrate specificity of AdoP, the active-site mutant D204N was prepared and kinetically characterized and the structures of the wild-type protein and the D204N mutant complexed with adenosine and sulfate or with inosine and sulfate were determined at high resolution (1.2-1.4 Å). AdoP interacts directly with the preferred substrate through a hydrogen-bond donation from the catalytically important residue Asp204 to N7 of the purine base. Comparison with Escherichia coli PNP revealed a more optimal orientation of Asp204 towards N7 of adenosine and a more closed active site. When inosine is bound, two water molecules are interposed between Asp204 and the N7 and O6 atoms of the nucleoside, thus allowing the enzyme to find alternative but less efficient ways to stabilize the transition state. The mutation of Asp204 to asparagine led to a significant decrease in catalytic efficiency for adenosine without affecting the efficiency of inosine cleavage. [ABSTRACT FROM AUTHOR]

Published
2012
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34. Renal purine efflux and xanthine oxidase activity during experimental nephrosis in rats: Difference between puromycin aminonucleoside and adriamycin nephrosis

Author

Ginevri, Fabrizio, primary, Gusmano, Rosanna, additional, Oleggini, Roberta, additional, Acerbo, Silvia, additional, Bertelli, Roberta, additional, Perfumo, Francesco, additional, Cercignani, Giovanni, additional, Allegrini, Simone, additional, D'Allegri, Franco, additional, and Ghiggeri, Gianmarco, additional

Published
1990
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35. Cytosolic 5′nucleotidase hyperactivity in erythrocytes of Lesch–Nyhan syndrome patients

Author

Pesi, Rossana, Micheli, Vanna, Jacomelli, Gabriella, Peruzzi, Luana, Camici, Marcella, Garcia-Gil, Mercedes, Allegrini, Simone, and Tozzi, Maria Grazia

Abstract

Lesch–Nyhan syndrome is a metabolic–neurological syndrome caused by the X-linked deficiency of the purine salvage enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRT). Metabolic consequences of HGPRT deficiency have been clarified, but the connection with the neurological manifestations is still unknown. Much effort has been directed to finding other alterations in purine nucleotides in different cells of Lesch–Nyhan patients. A peculiar finding was the measure of appreciable amount of Z-nucleotides in red cells. We found significantly higher IMP-GMP-specific 5′-nucleotidase activity in the erythrocytes of seven patients with Lesch–Nyhan syndrome than in healthy controls. The same alteration was found in one individual with partial HGPRT deficiency displaying a severe neurological syndrome, and in two slightly hyperuricemic patients with a psychomotor delay. Since ZMP was a good substrate of 5′-nucleotidase producing Z-riboside, we incubated murine and human cultured neuronal cells with this nucleoside and found that it is toxic for our models, promoting apoptosis. This finding suggests an involvement of the toxicity of the Z-riboside in the pathogenesis of neurological disorders in Lesch–Nyhan syndrome and possibly in other pediatric neurological syndromes of uncertain origin.

Published
2000

36. Purine-Metabolising Enzymes and Apoptosis in Cancer.

Author

Camici, Marcella, Garcia-Gil, Mercedes, Pesi, Rossana, Allegrini, Simone, and Tozzi, Maria Grazia

Subjects
PURINE metabolism, CELL proliferation, APOPTOSIS, ENZYMES, HYDROLASES, GENETIC mutation, NUCLEIC acids, NUCLEOTIDES, OXIDOREDUCTASES, TRANSFERASES, TUMORS
Abstract

The enzymes of both de novo and salvage pathways for purine nucleotide synthesis are regulated to meet the demand of nucleic acid precursors during proliferation. Among them, the salvage pathway enzymes seem to play the key role in replenishing the purine pool in dividing and tumour cells that require a greater amount of nucleotides. An imbalance in the purine pools is fundamental not only for preventing cell proliferation, but also, in many cases, to promote apoptosis. It is known that tumour cells harbour several mutations that might lead to defective apoptosis-inducing pathways, and this is probably at the basis of the initial expansion of the population of neoplastic cells. Therefore, knowledge of the molecular mechanisms that lead to apoptosis of tumoural cells is key to predicting the possible success of a drug treatment and planning more effective and focused therapies. In this review, we describe how the modulation of enzymes involved in purine metabolism in tumour cells may affect the apoptotic programme. The enzymes discussed are: ectosolic and cytosolic 5′-nucleotidases, purine nucleoside phosphorylase, adenosine deaminase, hypoxanthine-guanine phosphoribosyltransferase, and inosine-5′-monophosphate dehydrogenase, as well as recently described enzymes particularly expressed in tumour cells, such as deoxynucleoside triphosphate triphosphohydrolase and 7,8-dihydro-8-oxoguanine triphosphatase. [ABSTRACT FROM AUTHOR]

Published
2019
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