高同型半胱氨酸血症
同型半胱氨酸
硝化作用
半胱氨酸
化学
亚甲基四氢叶酸还原酶
生物化学
酶
医学
基因
基因型
有机化学
作者
Cheng-Hua Luo,Dengyu Ji,Li Yan,Yan Cao,Shangyue Zhang,Wenjing Yan,Ke Xue,Jiayin Chai,Ye Wu,Huirong Liu,Wen Wang
标识
DOI:10.1016/j.freeradbiomed.2020.12.440
摘要
Sp1-CSE-H2S pathway plays an important role in homocysteine-metabolism, whose disorder can result in hyperhomocysteinemia. H2S deficiency in hyperhomocysteinemia has been reported, while the underlying mechanism and whether it in turn affects the progress of hyperhomocysteinemia are unclear. This study focused on the post-translational modification of Sp1/CSE and revealed four major findings: (1) Homocysteine-accumulation augmented CSE's nitration, inhibited its bio-activity, thus caused H2S deficiency. (2) H2S deficiency inhibited the S-sulfhydration of Sp1, down-regulated CSE and decreased H2S further, which in turn weakened CSE's own S-sulfhydration. (3) CSE was S-sulfhydrated at Cys84, Cys109, Cys172, Cys229, Cys252, Cys307 and Cys310, among which the S-sulfhydration of Cys172 and Cys310 didn't affect its enzymatic activity, while the S-sulfhydration of Cys84, Cys109, Cys229, Cys252 and Cys307 was necessary for its bio-activity. (4) H2S deficiency trapped homocysteine-metabolism into a vicious cycle, which could be broken by either blocking nitration or restoring S-sulfhydration. This study detected a new mechanism that caused severe hyperhomocysteinemia, thereby provided new therapeutic strategies for hyperhomocysteinemia.
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