多胺氧化酶在多胺代谢中的作用

Roles of Polyamine Oxidases in Polyamine Catabolism

本文概括了精胺氧化酶和乙酰多胺氧化酶参与的主要的生化,细胞和生理过程,多胺氧化酶是黄素腺嘌呤二核苷酸包含酶,可以催化多胺和乙酰多胺的氧化,其底物的特异性和氧化产物的种类依赖于酶的来源.酵母菌的多胺氧化酶可以氧化精胺,N1-乙酰精胺,N1-乙酰亚精胺,然而在脊椎动物中,是由两个不同的多胺氧化酶亚家族分别承担了这些功能,即精胺氧化酶和乙酰多胺氧化酶,分别特异性地催化精胺和N1-乙酰精胺/N1-乙酰亚精胺的氧化.精胺氧化酶和乙酰多胺氧化酶高效参与多胺生物合成和降解的调节.因为多胺是细胞生长和分化的基础调节者,因此它们的体内平衡对细胞生命十分重要,而精胺氧化酶和乙酰多胺氧化酶则起到了调节体内多胺平衡的作用.精胺氧化酶和乙酰多胺氧化酶参与药物反应,细胞凋亡和应激反应,它们的异常可以改变多胺的体内平衡.多胺分解代谢的调节异常经常与包括癌症在内的几种病理状况有关.

The goal of this review is to cover the main biochemical, cellular and physiological processes in which SMO and APAO are involved. Polyamine oxidases （ PAOs） are flavin adenine dinucleotide-（ FAD-） containing enzymes that catalyze the oxidation of both acetylated and non-acetylated polyamines. The substrate specificity and the nature of the oxidation products depend on the source of the enzymes. PAO from yeast can oxidize spermine,N^1-acetylspermine,and N^1-acetylspermidine. However,in vertebrates these functions are ad-dressed by two specialized polyamine oxidase subfamilies, namely spermine oxidase （ SMO ） and acetylpolyamine oxidase（ APAO） . SMO and APAO specifically catalyze the oxidation of spermine and N^1-ace-tylspermine/N^1-acetylspermidine,respectively. SMO and APAO are involved in the highly regulated pathways of polyamine biosynthesis and degradation. Since polyamines are basic regulators of cell growth and prolifera-tion,their homeostasis is crucial for cell life. SMO and APAO play a dominant role in the highly regulated mammalian polyamines catabolism. SMO and APAO participate in drug response,apoptosis and etiology of sev-eral pathological conditions,including cancer. Their deregulation can alter polyamine homeostasis,and dysregu-lation of polyamine catabolism is often associated with several disease states.