Polyamine catabolism and disease.
Polyamine catabolism and disease.
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DOI：
10.1042/bj20090598
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发表时间：
2009-07-15
期刊：
影响因子：
--
通讯作者：
Pegg AE
中科院分区：
文献类型：
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作者：
Casero RA;Pegg AE
除了多胺体内平衡外，越来越清楚的是，多胺分解代谢在药物反应、细胞凋亡、应激刺激反应中起主导作用，并有助于包括癌症在内的几种病理状态的病因学。高诱导酶亚精胺/精胺n1 -乙酰转移酶（SSAT）和精胺氧化酶（SMO），以及通常组成性表达的n1 -乙酰多胺氧化酶（APAO），似乎在许多正常和疾病过程中发挥关键作用。多胺分解代谢的失调经常伴随着几种疾病状态，这表明这种失调既可以为疾病机制提供有用的见解，也可以为治疗提供独特的可药物靶点。这些酶中的每一种都有可能改变多胺稳态，以响应多种细胞信号，这两种氧化酶产生活性氧H2O2和醛，每一种都有可能产生病变。SSAT的活性有可能为APAO或多胺输出物提供底物，从而降低细胞内多胺浓度，其净效应取决于SSAT增加的幅度和速度。SSAT还可能通过与其他蛋白质的相互作用和干扰乙酰辅酶a和ATP的含量来影响细胞代谢。这篇综述的目的是涵盖那些可能影响疾病病因或治疗的多胺分解代谢方面，并为多胺生物学这一令人兴奋的方面提供坚实的背景。
In addition to polyamine homeostasis, it has become increasingly clear that polyamine catabolism can play a dominant role in drug response, apoptosis, response to stressful stimuli, and contribute to the etiology of several pathological states, including cancer. The highly inducible enzymes spermidine/spermine N1-acetyltransferase (SSAT) and spermine oxidase (SMO), and, the generally constitutively expressed N1-acetylpolyamine oxidase (APAO), appear to play critical roles in many normal and disease processes. The dysregulation of polyamine catabolism frequently accompanies several disease states and suggests that such dysregulation may both provide useful insight into disease mechanism and provide unique drugable targets that can be exploited for therapeutic benefit. Each of these enzymes has the potential to alter polyamine homeostasis in response to multiple cell signals and the two oxidases produce the reactive oxygen species H2O2 and aldehydes, each with the potential to produce pathologies. The activity of SSAT has the potential to provide substrates for APAO or substrates for the polyamine exporter, thus reducing the intracellular polyamine concentration, the net effect of which depends on the magnitude and rate of any increase in SSAT. SSAT may also influence cellular metabolism via interaction with other proteins and by perturbing the content of acetyl CoA and ATP. The goal of this review is to cover those aspects of polyamine catabolism that have potential to impact disease etiology or treatment and to provide a solid background in this ever more exciting aspect of polyamine biology.