Spermidine/spermine N1-acetyltransferase--the turning point in polyamine metabolism.
Polyamines are thought to have several vital roles in cell growth and differentiation. The highly regulated polyamine metabolic pathway provides cells with the ability to finely control the intracellular concentration of these ubiquitous polycations. Although earlier studies of regulation of polyamine content were concentrated on the biosynthetic reactions, recently the importance of the catabolic processes, particularly the highly regulated acetylation step in polyamine degradation, has become apparent. This work has led to an understanding of how a cell may, in a tightly controlled manner, facilitate the breakdown, excretion, cycling, and/or intracellular shuttling of the polyamines. This myriad of possibilities appears to be regulated initially at a single rate-limiting enzymatic step, the N1-acetylation of spermidine or spermine, by spermidine/spermine N1-acetyltransferase (SSAT). Recent cloning of the human SSAT gene has facilitated a more detailed study of this enzyme. SSAT appears to have a role in the determination of tumor sensitivity to a new class of antineoplastic agents. The further study of SSAT and the associated polyamine metabolism should provide a better understanding of the regulation and function of these cations.
Casero
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Johns Hopkins Oncology Center Laboratories, Johns Hopkins School of Medicine, Baltimore, Maryland.
Pegg
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D000107:Acetylation; D000123:Acetyltransferases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D000970:Antineoplastic Agents; D003001:Cloning, Molecular; D006801:Humans; D008969:Molecular Sequence Data; D011073:Polyamines / Q000378:metabolism*; D000099228:Diamine N-Acetyltransferase
D000123:Acetyltransferases; D000970:Antineoplastic Agents; D011073:Polyamines; D000099228:Diamine N-Acetyltransferase