Polyamine biosynthetic and catabolic enzymes

Polyamine biosynthetic and catabolic enzymes are a group of proteins that regulate the intracellular concentrations of polyamines, including putrescine, spermidine, and spermine. These enzymes, such as ornithine decarboxylase (ODC), S-adenosylmethionine decarboxylase (SAMDC), and spermidine/spermine N1-acetyltransferase (SSAT), are essential for maintaining polyamine homeostasis, which supports DNA stability, RNA transcription, and protein translation (Casero et al., 2018, Nature Reviews Cancer). Because polyamines are required for rapid cell growth, this pathway is frequently hijacked in cancer, where oncogenic signaling (e.g., by MYC) leads to the overproduction of polyamines to sustain tumor proliferation (Pegg, 2016, Journal of Biological Chemistry). Therapeutic targeting of these enzymes, most notably through the ODC inhibitor eflornithine (DFMO), has proven effective in treating African trypanosomiasis and was recently FDA-approved to reduce the risk of relapse in high-risk neuroblastoma (FDA, 2023). Beyond oncology, these enzymes are being investigated for their roles in inflammation and neurodegeneration, although drug development must address challenges like compensatory polyamine uptake from the diet and potential side effects such as ototoxicity (Brooks et al., 2022, Frontiers in Oncology).

Other names

Polyamine metabolism enzymesPolyamine biosynthetic pathwayPolyamine metabolic pathwayPolyamine pathway enzymes

The primary mechanism of action involves the irreversible or competitive inhibition of rate-limiting biosynthetic enzymes, such as ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase (SAMDC), to deplete intracellular polyamine concentrations (Casero et al., 2018, Nature Reviews Cancer). Alternatively, some agents act as polyamine mimetics that induce the catabolic enzyme spermidine/spermine N1-acetyltransferase (SSAT), leading to the depletion of natural polyamines through accelerated acetylation and subsequent export or oxidation (Pegg, 2016, Journal of Biological Chemistry).