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Antizyme Inhibitors in Polyamine Metabolism and Beyond: Physiopathological Implications

1
Department of Biochemistry and Molecular Biology B and Immunology, Faculty of Medicine, University of Murcia, 30100 Murcia, Spain
2
Laboratory of Cellular and Molecular Endocrinology, Institute of Biomedical Research in Malaga (IBIMA), Virgen de la Victoria University Hospital, 29010 Málaga, Spain
3
CIBER Physiopathology of Obesity and Nutrition (CIBERobn), Institute of Health Carlos III (ISCIII), 28029 Madrid, Spain
4
Biomedical Research Institute of Murcia (IMIB), 30120 Murcia, Spain
*
Author to whom correspondence should be addressed.
These authors contributed equally.
Med. Sci. 2018, 6(4), 89; https://doi.org/10.3390/medsci6040089
Received: 16 September 2018 / Revised: 2 October 2018 / Accepted: 4 October 2018 / Published: 9 October 2018
(This article belongs to the Special Issue Polyamine Metabolism in Disease and Polyamine-Targeted Therapies)
The intracellular levels of polyamines, cationic molecules involved in a myriad of cellular functions ranging from cellular growth, differentiation and apoptosis, is precisely regulated by antizymes and antizyme inhibitors via the modulation of the polyamine biosynthetic and transport systems. Antizymes, which are mainly activated upon high polyamine levels, inhibit ornithine decarboxylase (ODC), the key enzyme of the polyamine biosynthetic route, and exert a negative control of polyamine intake. Antizyme inhibitors (AZINs), which are proteins highly homologous to ODC, selectively interact with antizymes, preventing their action on ODC and the polyamine transport system. In this review, we will update the recent advances on the structural, cellular and physiological functions of AZINs, with particular emphasis on the action of these proteins in the regulation of polyamine metabolism. In addition, we will describe emerging evidence that suggests that AZINs may also have polyamine-independent effects on cells. Finally, we will discuss how the dysregulation of AZIN activity has been implicated in certain human pathologies such as cancer, fibrosis or neurodegenerative diseases. View Full-Text
Keywords: polyamines; polyamine metabolism; antizyme; antizyme inhibitors; ornithine decarboxylase polyamines; polyamine metabolism; antizyme; antizyme inhibitors; ornithine decarboxylase
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Ramos-Molina, B.; Lambertos, A.; Peñafiel, R. Antizyme Inhibitors in Polyamine Metabolism and Beyond: Physiopathological Implications. Med. Sci. 2018, 6, 89.

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