Polyamine catabolism and disease

Abstract

In addition to polyamine homeostasis, it has become increasingly clear that polyamine catabolism can play a dominant role in drug response, apoptosis, response to stressful stimuli, and contribute to the etiology of several pathological states, including cancer. The highly inducible enzymes spermidine/spermine N1-acetyltransferase (SSAT) and spermine oxidase (SMO), and, the generally constitutively expressed N1-acetylpolyamine oxidase (APAO), appear to play critical roles in many normal and disease processes. The dysregulation of polyamine catabolism frequently accompanies several disease states and suggests that such dysregulation may both provide useful insight into disease mechanism and provide unique drugable targets that can be exploited for therapeutic benefit. Each of these enzymes has the potential to alter polyamine homeostasis in response to multiple cell signals and the two oxidases produce the reactive oxygen species H2O2 and aldehydes, each with the potential to produce pathologies. The activity of SSAT has the potential to provide substrates for APAO or substrates for the polyamine exporter, thus reducing the intracellular polyamine concentration, the net effect of which depends on the magnitude and rate of any increase in SSAT. SSAT may also influence cellular metabolism via interaction with other proteins and by perturbing the content of acetyl CoA and ATP. The goal of this review is to cover those aspects of polyamine catabolism that have potential to impact disease etiology or treatment and to provide a solid background in this ever more exciting aspect of polyamine biology.

Pharmacological and dietary agents for colorectal cancer chemoprevention: Effects on polyamine metabolism (Review)

“…The increase is due to the loss in polyamine homeostasis occurring during the dysregulation of cell proliferation (2). This is also proven by evidence of an upregulation of polyamine biosynthesis (14), a decrease in their catabolism (15,16) and an increased uptake (17). Since polyamine metabolism is an integral component of the mechanism of the carcinogenesis in colorectal tissue, polyamine levels and ODC activity have been considered even as specific markers for neoplastic proliferation in the colon (18).…”

Homocysteine and Polyamines: Metabolic Relationship and Its Clinical Significance in Folate Inhibitors Chemotherapy

“…Являясь поликатионами, они стабилизируют струк-туру ДНК и макромолекул в процессах репликации и биосинтеза белка. Также показано повышение концентрации полиаминов в плазме крови при раз-личных опухолевых процессах [62][63][64][65][66][67][68][69]. Поскольку полиамины играют важную роль в процессах опу-холевой пролиферации, в последние годы они активно используются в качестве терапевтической мишени для поиска новых противоопухолевых пре-паратов [69][70][71].…”

Pyruvate-Dependent Changes in Neutrophil Amino- and Alpha-Keto Acid Profiles or Immunity: Which Mechanisms Are Involved?

“…It is believed that polyamines may have specific roles in cellular protein biosynthesis, growth, proliferation and apoptosis processes, for instance through the stabilization of cellular DNA and RNA through the binding of spermine and spermidine. And equally in other leukocytes, the need for polyamines is covered by both, transport from the extracellular matrix (here the capacity in leukocytes is low) as well as synthesis (spermine synthesis after enzymatic decarboxylation of ornithine by ornithine-decarboxylase) [55]- [59]. Nevertheless, their precise metabolic functions in human neutrophils are still virtually undiscovered.…”