Polyamine

Polyamines are small, positively charged organic compounds that contain multiple amine groups. At physiological pH these molecules carry multiple positive charges, enabling interactions with negatively charged macromolecules such as DNA, RNA, and proteins. The most abundant polyamines in most organisms are putrescine (1,4-diaminobutane), spermidine, and spermine. In some species, longer or additional polyamines such as thermospermine or norspermidine also occur.

Biologically, polyamines are essential for cell growth and function. They influence DNA stabilization and packaging, regulate transcription and translation, modulate ion channels and enzyme activities, and support processes such as differentiation and development. They are found in all kingdoms of life and play regulatory roles in plants, bacteria, and animals. Polyamine levels are tightly controlled, reflecting their importance to cellular homeostasis.

Biosynthesis and metabolism typically proceed from ornithine to putrescine via ornithine decarboxylase, after which spermidine and then spermine are formed by the successive transfer of aminopropyl groups donated by decarboxylated S-adenosylmethionine. The enzymes ornithine decarboxylase and S-adenosylmethionine decarboxylase are key rate-limiting steps. Polyamines are also acquired from the diet and gut microbiota. Degradation occurs through amine oxidases and acetyltransferases, and the cellular pool is balanced by transport mechanisms that can import or export polyamines.

Clinical and research interest arises from the observation that elevated polyamine levels are associated with cell proliferation and cancer, while depletion of polyamines can inhibit tumor growth. Inhibitors of ornithine decarboxylase, such as difluoromethylornithine (DFMO), have been explored as therapeutic agents. Overall, polyamines are essential, evolutionarily conserved components of cellular physiology, with broad implications for growth, development, and disease.