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Diamine acetyltransferase 1 (SAT1), also known as spermidine/spermine N1-acetyltransferase (SSAT1), is the rate-limiting enzyme in the catabolic pathway of polyamines [UniProt: P21673]. It catalyzes the N1-acetylation of spermidine and spermine, which promotes their excretion from the cell or their oxidation by polyamine oxidase, thus playing a vital role in maintaining polyamine homeostasis [PubMed: 15591236]. In the context of oncology, SAT1 is a target for polyamine analogues like DENSpm, which super-induce the enzyme to deplete intracellular polyamine pools, leading to cell cycle arrest and apoptosis [PubMed: 12140261]. Furthermore, SAT1 mRNA has been identified as a prominent peripheral biomarker for suicidal ideation and mood disorders, reflecting its involvement in the biological response to stress [PubMed: 23958958]. Mutations in the SAT1 gene are also linked to Keratosis follicularis spinulosa decalvans, an X-linked disorder [NCBI Gene: 6303]. The enzyme's activity is highly regulated at the transcriptional, translational, and post-translational levels, making it a sensitive indicator of cellular metabolic status.
Induction of SAT1 expression by polyamine analogues leads to the rapid acetylation and subsequent depletion of intracellular polyamines, which are essential for cell proliferation, thereby inducing apoptosis and growth arrest in malignant cells [PubMed: 15591236].
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