Molecular insights into primary hyperoxaluria type i pathogenesis
Molecular insights into primary hyperoxaluria type i pathogenesis
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DOI：
10.2741/3948
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发表时间：
2012-01-01
影响因子：
3.1
通讯作者：
Montioli, Riccardo
中科院分区：
文献类型：
--
作者：
Cellini, Barbara;Oppici, Elisa;Montioli, Riccardo
原发性高尿酸1型（PH 1）是一种罕见的乙醛酸代谢常染色体隐性遗传病，由肝脏过氧化物酶体丙氨酸：乙醛酸转氨酶（AGT）（一种吡哆醛5 '-磷酸（PLP）依赖性酶）缺乏引起。PH 1发病机制主要是由于AGXT基因上的单点突变（迄今已鉴定出150多个），其特征在于基因型、酶和临床表型方面的显著异质性。本文介绍了一个最新的审查选定的两个等位基因形式的AGT和一些PH 1引起的变异体的生化特性的方面。这些最近的发现突出了致病性突变在蛋白质水平上的影响，并且与以前的细胞生物学和临床数据一起，（i）提高了对PH 1发病机制的分子基础的理解，以及（ii）有助于描绘预测对吡哆醇治疗的反应或为携带分析的突变的PH 1患者提出新策略的前景。
Primary hyperoxaluria type 1 (PH1) is a rare autosomal recessive disorder of glyoxylate metabolism caused by the deficiency of liver peroxisomal alanine: glyoxylate aminotransferase (AGT), a pyridoxal 5'-phosphate (PLP)-dependent enzyme. The PH1 pathogenesis is mostly due to single point mutations (more than 150 so far identified) on the AGXT gene, and is characterized by a marked heterogeneity in terms of genotype, enzymatic and clinical phenotypes. This article presents an up to date review of selected aspects of the biochemical properties of the two allelic forms of AGT and of some PH1-causing variants. These recent discoveries highlight the effects at the protein level of the pathogenic mutations, and, together with previous cell biology and clinical data, (i) improve the understanding of the molecular basis of PH1 pathogenesis, and (ii) help to delineate perspectives for predicting the response to pyridoxine treatment or for suggesting new strategies for PH1 patients bearing the analyzed mutations.