Mammalian polyamine metabolism and function

Abstract

SummaryPolyamines are ubiquitous small basic molecules that play multiple essential roles in mammalian physiology. Their cellular content is highly regulated and there is convincing evidence that altered metabolism is involvement in many disease states. Drugs altering polyamine levels may therefore have a variety of important targets. This review will summarize the current state of understanding of polyamine metabolism and function, the regulation of polyamine content, and heritable pathological conditions that may be derived from altered polyamine metabolism.

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

“…The function of spermine and spermidine in SRS disease etiology is not yet fully elucidated, but it might be speculated that the altered spermine/spermidine ratio may severely affect the balance between excitatory and inhibitory mechanisms and result in cerebral dysfunction such as epilepsy. Spermine and spermidine regulate brain glutamate receptors including N-methyl-D-aspartate (NMDA), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and kainate receptors that are involved in excitatory synaptic transmission (Pegg 2009;Igarashi and Kashiwagi 2010). Spermine activates the endogenous phosphorylation and function of the GABA A receptor (SidAhmed-Mezi et al 2010).…”

A role for polyamine regulators in ESC self-renewal

“…23 The levels of the polyamines are tightly regulated at the level of synthesis, uptake, degradation and secretion. 29 The two rate-limiting enzymes in their synthesis are ODC1 and AMD1. ODC1 (ornithine decarboxylase) decarboxylates ornithine to putrescine, which is converted into the higher order polyamines, spermidine and spermine.…”

“…The levels of dcAdoMet are generally significantly lower than the levels of AdoMet, and, once produced, it is directed to the polyamine synthesis pathway. 29 Increased dcAdoMet will enable higher levels of spermine and spermidine to be produced, both of which impact on a variety of biological processes. Increased spermidine also promotes the levels of the modified amino acid hypusine that is present in the translation factor EIF5A and is required for its function.…”

“…EIF5A is important for growth and protein synthesis and has recently been shown to function as a tumor suppressor. 29,33 AMD1 activity has been shown to impact the levels of hypusinated EIF5A, and the addition of an inhibitor to AMD1 resulted in decreased spermidine levels and a decrease in the levels of hypusine-containing EIF5A. 34 In addition to being required for regulators of ESCs, more recently, a variety of screening methods have identified new stem cell regulators that function outside the nucleus.…”

Spermidine: a physiological autophagy inducer acting as an anti-aging vitamin in humans?

“…Within mammalian cells, spermidine is generated from its precursor putrescine (which itself is generated from ornithine) or by oxidative degradation of spermine [2,3,28]. The net cytosolic spermidine content further depends on its catabolism, which is mainly driven by acetylation and subsequent oxidation [29–31], but also on its uptake from the extracellular space and its excretion by the cell.…”