丙酮酸脱氢酶活性缺失与疾病发生的研究进展

Advances of pyruvate dehydrogenase inactivation and disease occurrence

丙酮酸脱氢酶系(pyruvate dehydrogenase complex,PDH_C)主要由丙酮酸脱氢酶(E1)、二氢硫辛酸乙酰转移酶(E2)、二氢硫辛酸脱氢酶(E3)和E3结合蛋白(E3BP)组成,绝大多数的丙酮酸脱氢酶系缺失都是由丙酮酸脱氢酶E1α亚基突变或者磷酸化引起,仅有少数突变发生在E2、E3和E3BP上。本文就PDHC的结构与功能,PDHA1基因突变和E1α磷酸化与其功能的关系,及在相关疾病包括肿瘤的发生、发展和转移中的分子机制的研究进展做一总结,以期对因E1α功能丧失引起的疾病的诊断与治疗有所借鉴意义。

Pyruvate dehydrogenase complex（PDHC） is mainly composed of pyruvate dehydrogenase（E1）,dihydrolipoamide acetyltransferase（E2）,dihydrolipoamide dehydrogenase（E3） and E3 binding protein（E3 BP）.Most of the pyruvate dehydrogenase deficiency is caused by pyruvate dehydrogenase E1α subunit mutation or its phosphorylation,whereas the mutation of E2,E3,or E3 BP is less frequency.The present review summarizes the relationship of PDHC between structure and function,and the relationship of PDHA1 mutations,E1α phosphorylation and its function.The molecular mechanisms of E1α inactivation are updated in tumorigenesis,development,and metastasis.