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Mammalian Polyamine Catabolism

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Polyamines

Abstract

Intracellular mammalian polyamine catabolism occurs through two distinct pathways, both of which culminate in oxidation reactions that generate highly reactive, potentially toxic by-products. In the back-conversion to spermidine, spermine can either undergo direct oxidation by spermine oxidase (SMOX) or be acetylated by spermidine/spermine N 1-acetyltransferase (SSAT), followed by subsequent oxidation by acetylpolyamine oxidase (APAO). Spermidine undergoes acetylation and oxidation back to putrescine through this same SSAT/APAO pathway. Polyamines are absolutely essential for cell viability and proliferation, and polyamine biosynthesis and intracellular concentrations are frequently upregulated in hyperproliferative conditions such as cancer. As a result, many studies have successfully focused on the induction of polyamine catabolism as a rational target for antiproliferative chemotherapeutic intervention. However, it is also becoming apparent that chronically elevated levels of polyamine catabolism in nontumorigenic cells can have disease implications. A variety of stimuli, including microbial pathogens, inflammatory signals, and tissue injury, have now been identified to induce the polyamine catabolic enzymes. In addition to the back-conversion of polyamines, these reactions also release the reactive oxygen species precursor hydrogen peroxide as well as potentially toxic aldehydes. These metabolites as well as the reduction in spermine and spermidine levels can have deleterious physiological effects resulting in the manifestation and promotion of multiple pathologies. This chapter focuses on recent discoveries in the regulation of the mammalian polyamine catabolic enzymes and the pathophysiological effects of this upregulation.

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Authors and Affiliations

  1. The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Bunting Blaustein Building, 1650 Orleans Street, Room 551, Baltimore, MD, 21287, USA

    Tracy Murray-Stewart & Robert A. Casero Jr.

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  1. Tracy Murray-Stewart
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  2. Robert A. Casero Jr.
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Correspondence to Robert A. Casero Jr. .

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  1. Graduate School of Life Sciences, Tohoku University, 2-1-1 Katahira, Aoba, Sendai-city, Miyagi, Japan

    Tomonobu Kusano

  2. Graduate School of Science and Technology, Kyoto Institute of Technology, Goshokaido-cho, Matsugasaki, Sakyo-ku, Kyoto, Japan

    Hideyuki Suzuki

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Murray-Stewart, T., Casero, R.A. (2015). Mammalian Polyamine Catabolism. In: Kusano, T., Suzuki, H. (eds) Polyamines. Springer, Tokyo. https://doi.org/10.1007/978-4-431-55212-3_5

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