哺乳动物的基因识别和生化特性聚胺氧化酶参与聚胺back-conversion。
文章的细节
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引用
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梁Vujcic S, P, Diegelman P,克莱默DL,波特连续波
哺乳动物的基因识别和生化特性聚胺氧化酶参与聚胺back-conversion。
j . 2003 2月15日,370 (Pt 1): 19-28。
- PubMed ID
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12477380 (在PubMed]
- 文摘
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在聚胺back-conversion通路、精胺和亚精胺是由亚精胺和精胺乙酰化N1乙酰转移酶(SSAT),然后由聚胺氧化酶氧化(PAO)分别产生亚精胺和腐胺。尽管PAO第一净化二十多年前,蛋白质尚未与基因组序列。在目前的研究中,我们应用一个搜索策略来识别小说氧化酶序列位于人类10和鼠标染色体7号染色体。哺乳动物同源互补源自人类大脑和鼠标乳腺肿瘤是大约的推导出编码蛋白质。55 kDa有82%的序列的身份。当cDNA瞬变转染进hek - 293细胞,细胞内精胺池下降了约。30%,而亚精胺2-4-fold增加。溶菌产物人类PAO cDNA-transfected hek - 293细胞,但不是vector-transfected细胞,迅速氧化N1-acetylspermine亚精胺。底物特异性决定的溶解产物测定显示偏好排名N1-acetylspermine = N1-acetylspermidine > N1, N12-diacetylspermine > >精胺;亚精胺没有采取行动。 This ranking is identical to that reported for purified PAO and distinctly different from the recently identified spermine oxidase (SMO), which prefers spermine over N1-acetylspermine. Monoethyl- and diethylspermine analogues also served as substrates for PAO, and were internally cleaved adjacent to a secondary amine. We deduce that the present oxidase sequences are those of the FAD-dependent PAO involved in the polyamine back-conversion pathway. In Northern blot analysis, PAO mRNA was much less abundant in HEK-293 cells than SMO or SSAT mRNA, and all three were differentially induced in a similar manner by selected polyamine analogues. The identification of PAO sequences, together with the recently identified SMO sequences, provides new opportunities for understanding the dynamics of polyamine homoeostasis and for interpreting metabolic and cellular responses to clinically-relevant polyamine analogues and inhibitors.