Biosynthesis of spermidine and spermine

The polyamines spermidine and spermine are expressed in a variety of tissues and are involved in the regulation of apoptosis, cellular proliferation, and progression through the cell cycle. Depletion of polyamines appears to reduce cell growth, and increased polyamine expression is associated with the cancer development and progression, making polyamine biosynthesis a target for the control of cancer. As positively charged amines, spermine and spermidine interact with DNA and may exert some of their effects through this interaction. Ornithine, one of the starting materials for polyamine biosynthesis, is derived from the amino acid arginine as part of the urea cycle. The enzyme ornithine decarboxylase produces putrescine from ornithine. Amino-propyl groups from decarboxylated adoMet are progressively added to putrescine to produce first spermidine and then spermine. Ornithine decarboxylase expression appears to be induced in some types of cancer, particularly skin cancer, and ODC inhibition to cause tumor regression.

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REFERENCES: Thomas, T. and Thomas, T.J. (2001) Polyamines in cell growth and cell death: molecular mechanisms and therapeutic applications. Cell Mol Life Sci 58(2):244-58