Polyamine metabolism in a member of the phylum Microspora (Encephalitozoon cuniculi):: effects of polyamine analogues
Polyamine metabolism in a member of the phylum Microspora (Encephalitozoon cuniculi):: effects of polyamine analogues
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DOI：
10.1099/mic.0.26889-0
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发表时间：
2004-05-01
期刊：
影响因子：
2.8
通讯作者：
Wittner, M
中科院分区：
文献类型：
--
作者：
Bacchi, CJ;Rattendi, D;Wittner, M
多胺的摄取，生物合成和catalysts在微孢子虫寄生虫兔脑炎原虫详细参考的多胺的寡胺和芳胺类似物的影响。桨编码器家兔是哺乳动物细胞的细胞内寄生虫，具有多胺代谢的生物合成和分解代谢酶，如成熟孢子的无细胞提取物所示。多胺的吸收测定在不成熟的，前从宿主细胞分离出的孢子，Percoll梯度。精胺被迅速吸收，并通过亚精胺/精胺N-1-乙酰转移酶（SSAT）和多胺氧化酶（PAO）代谢为亚精胺和一种未知物质（可能是乙酰氨基丙醛）。大多数亚精胺和未知产物在细胞孵育培养基中发现，表明它们从细胞中释放出来。多胺的双（乙基）低聚胺类似物，例如SL-111144和SIL-111158，以及芳胺类似物[BW-1，双（苯基苄基）3-7-3类似物]在微摩尔水平上阻止精胺的吸收和相互转化，并且在BW-1的情况下，充当PAO的底物。Enc。家兔PAO活性在最适pH、底物特异性和对已知PAO抑制剂的敏感性方面不同于哺乳动物细胞中发现的PAO活性。SL-11158抑制SSAT活性的混合型抑制，其中类似物对酶的亲和力比天然底物精胺高70倍。对Enc的兴趣。家兔多胺代谢和这些多胺类似物的生物化学作用是有保证的，因为它们治愈了Enc的模型感染。在小鼠中的cuniculi，并且是用于人类临床试验的潜在候选者。
The uptake, biosynthesis and catabolism of polyamines in the microsporidian parasite Encephalitozoon cuniculi are detailed with reference to the effects of oligoamine and arylamine analogues of polyamines. Enc. cuniculi, an intracellular parasite of mammalian cells, has both biosynthetic and catabolic enzymes of polyamine metabolism, as demonstrated in cell-free extracts of mature spores. The uptake of polyamines was measured in immature, pre-emergent spores isolated from host cells by Percoll gradient. Spermine was rapidly taken up and metabolized to spermidine and an unknown, possibly acetamidopropanal, by spermidine/spermine N-1-acetyltransferase (SSAT) and polyamine oxidase (PAO). Most of the spermidine and the unknown product were found in the cell incubation medium, indicating they were released from the cell. bis(Ethyl) oligoamine analogues of polyamines, such as SL-111144 and SIL-111158, as well as arylamine analogues [BW-1, a bis(phenylbenzyl) 3-7-3 analogue] blocked uptake and interconversion of spermine at micromolar levels and, in the case of BW-1, acted as substrate for PAO. The Enc. cuniculi PAO activity differed from that found in mammalian cells with respect to pH optimum, substrate specificity and sensitivity to known PAO inhibitors. SL-11158 inhibited SSAT activity with a mixed type of inhibition in which the analogue had a 70-fold higher affinity for the enzyme than the natural substrate, spermine. The interest in Enc. cuniculi polyamine metabolism and the biochemical effects of these polyamine analogues is warranted since they cure model infections of Enc. cuniculi in mice and are potential candidates for human clinical trials.