Molecular characterization of the AdeI mutant of Chinese hamster ovary cells: a cellular model of adenylosuccinate lyase deficiency.
Molecular characterization of the AdeI mutant of Chinese hamster ovary cells: a cellular model of adenylosuccinate lyase deficiency.
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DOI：
10.1016/j.ymgme.2010.08.022
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发表时间：
2011-01
影响因子：
3.8
通讯作者：
Patterson, David
中科院分区：
文献类型：
--
作者：
Vliet, Lydia K.;Wilkinson, Terry G., II;Duval, Nathan;Vacano, Guido;Graham, Christine;Zikanova, Marie;Skopova, Vaclava;Baresova, Veronika;Hnizda, Ales;Kmoch, Stanislav;Patterson, David
腺苷酸琥珀酸裂解酶（ADSL，E. C. 4.3.2.2在人类中，ADSL的突变导致先天性代谢缺陷，最初的特征是发育迟缓，通常具有自闭症特征。目前还没有有效的治疗ADSL缺陷的方法。关于发病机制的假设包括高水平的SAICAR、AMPS或其代谢物的毒性、从头嘌呤生物合成途径的缺陷或肌肉和大脑中缺乏完全功能性的嘌呤循环。了解ADSL缺陷的一个重要方法是开发细胞培养模型，允许在细胞水平上调查ADSL突变体的特性和ADSL缺陷的后果。我们以前曾报道过中国仓鼠卵巢（CHO-K1）细胞（Ade I）突变体的分离和初步表征，这些突变体缺乏可检测的ADSL活性，积累SAICAR和AMPS，并需要腺嘌呤生长。在这里，我们报告的cDNA序列的ADSL从CHO-K1和Ade I细胞，并描述了突变导致丙氨酸缬氨酸氨基酸取代位置291（A291V）在Ade I ADSL。这种取代位于ADSL的“签名序列”中，使酶失活，并验证Ade I作为ADSL缺陷的细胞模型。
Adenylosuccinate lyase (ADSL, E. C. 4.3.2.2) carries out two non-sequential steps in de novo AMP synthesis, the conversion of succinylaminoimidazole carboxamide ribotide (SAICAR) to aminoimidazolecarboxamide ribotide (AICAR) and the conversion of succinyl AMP (AMPS) to AMP. In humans, mutations in ADSL lead to an inborn error of metabolism originally characterized by developmental delay, often with autistic features. There is no effective treatment for ADSL deficiency. Hypotheses regarding the pathogenesis include toxicity of high levels of SAICAR, AMPS, or their metabolites, deficiency of the de novo purine biosynthetic pathway, or lack of a completely functional purine cycle in muscle and brain. One important approach to understand ADSL deficiency is to develop cell culture models that allow investigation of the properties of ADSL mutants and the consequences of ADSL deficiency at the cellular level. We previously reported the isolation and initial characterization of mutants of Chinese hamster ovary (CHO-K1) cells (Ade I) that lack detectable ADSL activity, accumulate SAICAR and AMPS, and require adenine for growth. Here we report the cDNA sequences of ADSL from CHO-K1 and Ade I cells and describe a mutation resulting in an alanine to valine amino acid substitution at position 291 (A291V) in Ade I ADSL. This substitution lies in the “signature sequence” of ADSL, inactivates the enzyme, and validates Ade I as a cellular model of ADSL deficiency.
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影响因子：
4.2
作者：
Sempere, Angela;Arias, Angela;Campistol, Jaume
通讯作者：
Campistol, Jaume
影响因子：
5.2
作者：
Gitiaux, Cyril;Ceballos-Picot, Irene;Bahi-Buisson, Nadia
通讯作者：
Bahi-Buisson, Nadia
DOI：
10.1073/pnas.85.23.8998
发表时间：
1988-12-01
影响因子：
11.1
作者：
FROHMAN, MA;DUSH, MK;MARTIN, GR
通讯作者：
MARTIN, GR
影响因子：
8
作者：
Sivendran, Sharmila;Colman, Roberta F.
通讯作者：
Colman, Roberta F.
影响因子：
4.7
作者：
Prudencio, Mercedes;Durazo, Armando;Borchelt, David R.
通讯作者：
Borchelt, David R.