The function of spermine

Abstract

Polyamines play important roles in cell physiology including effects on the structure of cellular macromolecules, gene expression, protein function, nucleic acid and protein synthesis, regulation of ion channels, and providing protection from oxidative damage. Vertebrates contain two polyamines, spermidine and spermine, as well as their precursor, the diamine putrescine. Although spermidine has an essential and unique role as the precursor of hypusine a post-translational modification of the elongation factor eIF5A, which is necessary for this protein to function in protein synthesis, no unique role for spermine has been identified unequivocally. The existence of a discrete spermine synthase enzyme that converts spermidine to spermine suggest that spermine must be needed and this is confirmed by studies with Gy mice and human patients with Snyder-Robinson syndrome in which spermine synthase is absent or greatly reduced. In both cases, this leads to a severe phenotype with multiple effects among which are intellectual disability, other neurological changes, hypotonia, and reduced growth of muscle and bone. This review describes these alterations and focuses on the roles of spermine which may contribute to these phenotypes including reducing damage due to reactive oxygen species, protection from stress, permitting correct current flow through inwardly rectifying K 1 channels, controlling activity of brain glutamate receptors involved in learning and memory, and affecting growth responses. Additional possibilities include acting as storage reservoir for maintaining appropriate levels of free spermidine and a possible non-catalytic role for spermine synthase protein.

Intracellular spermine blocks TRPC4 channel via electrostatic interaction with C-terminal negative amino acids

“…While various TRPC channels conduct dynamic physiological functions, one of the most prominent cases is the role of TRPC4 and TRPC6 in gastrointestinal (GI) physiology, especially in ileum myocytes [16,30,36]. Muscarinic cationic current (mI cat) , a cationic current evoked by muscarinic stimulation, in murine ileal myocyte had been heavily studied to identify its molecular candidates.…”

Polyamines in Eukaryotes, Bacteria, and Archaea

“…An important question that requires addressing in eukaryotes is whether there are functions of Spd in addition to modifying eIF5A and serving as a precursor of tetraamine biosynthesis. In addition, the in vivo molecular functions of Spm and Tspm are still unknown, although Spm is essential for mouse development (98) and Tspm is essential for normal growth and development of A. thaliana (32). Intriguingly, Spm is not required for normal laboratory growth of yeast and A. thaliana.…”

N8‐acetylspermidine as a potential plasma biomarker for Snyder‐Robinson syndrome identified by clinical metabolomics

“…Furthermore both spermine and spermidine are potent blockers of voltage-gated Na + channels and their pharmacological depletion leads to increased epileptogenic activity in pyramidal neurons (Fleidervish et al 2008). Modulation of NMDA receptors was further implicated in the etiology of intellectual disability (Igarashi and Kashiwagi 2010;Pegg 2014). Other SRS phenotypic aspects such as osteoporosis and deafness are explained by the involvement of spermine and spermidine in the regulation of osteoclastic activity and endocochlear potential homeostasis (Wang et al 2009;Yamamoto et al 2012).…”