Polyamine catabolism and oxidative damage

Abstract

Polyamines (PAs) are indispensable polycations ubiquitous to all living cells. Among their many critical functions, PAs contribute to the oxidative balance of the cell. Beginning with studies by the Tabor laboratory in bacteria and yeast, the requirement for PAs as protectors against oxygen radical-mediated damage has been well established in many organisms, including mammals. However, PAs also serve as substrates for oxidation reactions that produce hydrogen peroxide (H₂O₂) both intra- and extracellularly. As intracellular concentrations of PAs can reach millimolar concentrations, the H₂O₂ amounts produced through their catabolism, coupled with a reduction in protective PAs, are sufficient to cause the oxidative damage associated with many pathologies, including cancer. Thus, the maintenance of intracellular polyamine homeostasis may ultimately contribute to the maintenance of oxidative homeostasis. Again, pioneering studies by Tabor and colleagues led the way in first identifying spermine oxidase in Saccharomyces cerevisiae. They also first purified the extracellular bovine serum amine oxidase and elucidated the products of its oxidation of primary amine groups of PAs when included in culture medium. These investigations formed the foundation for many polyamine-related studies and experimental procedures still performed today. This Minireview will summarize key innovative studies regarding PAs and oxidative damage, starting with those from the Tabor laboratory and including the most recent advances, with a focus on mammalian systems.

Keywords: antioxidant; cancer biology; free radicals; homeostasis; oxidase; oxidative stress; polyamine; polyamine catabolism; reactive oxygen species (ROS); redox regulation; spermidine; spermine.

Figure 1.

Polyamine catabolic pathway in mammals. SSAT catalyzes the acetyl-group transfer from acetyl-CoA to the aminopropyl end of spermidine or spermine, producing N¹-acetylspermidine or N¹-acetylspermine, respectively. These acetylated PAs are either excreted from the cell or used as substrates for PAOX, producing H₂O₂, 3-acetoamidopropanal, and either putrescine or spermidine, depending on the starting substrate. Alternatively, spermine can be directly oxidized back to spermidine by SMOX while generating H₂O₂ and 3-aminopropanal.

Figure 2.

Extracellular polyamine oxidation. BSAO oxidizes the terminal aminopropyl nitrogens of spermine or spermidine (shown) to produce H₂O₂, ammonia, and the corresponding amino aldehydes.