Research Information System
Molecular Biology Reports, vol.53, no.1, 2026 (SCI-Expanded, Scopus)
Spermine synthase (Sms), a key enzyme in polyamine biosynthesis, catalyzes the conversion of spermidine to spermine using decarboxylated S-adenosylmethionine (dcAdoMet) as an aminopropyl donor. Although Sms is well-characterized in eukaryotes, it is relatively rare in bacteria, where spermine in some species is probably produced by non-specific aminopropyltransferases. In humans, SMS mutations cause Snyder-Robinson syndrome (SRS), an X-linked disorder characterized by intellectual disability, osteoporosis, and neurological dysfunction due to disrupted polyamine homeostasis. Structural studies reveal that Sms functions as a dimer, with its N-terminal domain essential for enzymatic activity. Loss of Sms leads to spermine deficiency, elevated spermidine levels, and metabolic imbalances, contributing to SRS pathology. Therapeutic strategies under investigation include rebalancing spermidine/spermine ratio, polyamine biosynthesis inhibitors (e.g., DFMO), antioxidants and gene therapy using AAV vectors. Conversely, in multiple cancer types, Sms overexpression promotes tumor progression by altering polyamine metabolism, activating oncogenic pathways (e.g., AKT, mTOR), and facilitating immune evasion. Elevated Sms expression correlates with poor prognosis in colorectal, pancreatic, hepatocellular, and head and neck cancers, highlighting its potential as a therapeutic target. However, spermine’s role is context-dependent, exhibiting both pro-tumorigenic and cytotoxic effects. While inhibition of Sms may suppress cancer growth, its deficiency in SRS underscores the delicate balance required in polyamine regulation. Insights from SRS and cancer studies highlight Sms as a critical enzyme in cellular homeostasis, with therapeutic implications for both degenerative and proliferative diseases. Further research is needed to elucidate its complex role and optimize targeted interventions.