甘氨酸-N-甲基转移酶对肝脏代谢及相关疾病的调控机制  

The Regulation Mechanism of Glycine-N-methyltransferase on Liver Metabolism and Related Diseases

作　　者：杜雪儿 王建国[2] 姚军虎[1] 曹阳春[1] DU Xue-Er;WANG Jian-Guo;YAO Jun-Hu;CAO Yang-Chun(College of Animal Science and Technology,Northwest A&F University,Yangling 712100,China;College of Veterinary Medicine,Northwest A&F University,Yangling 712100,China)

机构地区：[1]西北农林科技大学动物科技学院,杨凌712100 [2]西北农林科技大学动物医学院,杨凌712100

出　　处：《农业生物技术学报》2022年第11期2224-2235,共12页Journal of Agricultural Biotechnology

基　　金：国家自然科学基金(31972592);陕西省重点研发计划(2021NY-019);榆林市科技计划项目(CXY-2020-075)。

摘　　要：肝脏是人体重要的功能器官,能够进行多种物质的代谢并重新转运至机体其他部位进行利用和排泄,具有解毒及多种物质的合成、代谢、消化和储存等生理功能。其中脂肪与能量代谢尤为重要,如果该过程出现异常,包括脂肪合成过多、代谢减少及转运能力下降等,就会使非酒精性脂肪性肝病、肝纤维化及肝硬化、胆汁淤积,甚至肝细胞癌等多种疾病的发生风险急速上升,且与其他代谢类疾病的诱发也紧密关联。最近的研究表明肝脏中的甘氨酸-N-甲基转移酶(glycine-N-methyltransferase,GNMT)作为调控S-腺苷甲硫氨酸(S-adenosyl-L-methionine,SAM)向S-腺苷高半胱氨酸(S-adenosylhomocysteine,SAH)转化的关键酶来影响SAM的在体水平,进而调控机体的甲基化状态,GNMT还能调控脂肪代谢与转运相关基因的表达,以及氧化呼吸复合物Ⅱ的活性来调控脂肪含量,降低疾病发生和进一步发展。本文对GNMT在肝脏中的脂代谢、糖代谢及氧化应激等调控作用进行阐述,同时还讨论了GNMT在多种肝脏疾病中发挥的治疗作用,期望可以为今后针对GNMT的治疗方法及靶点夯实理论基础。The liver,a vital functional organ of the human body,can metabolize various substances and transport them to other parts of the body for utilization and excretion.It also has a plenty of physiological functions such as detoxification and the synthesis,metabolism,digestion and storage of various substances.Among them,fat and energy metabolism are particularly important.If this process becomes abnormal,including excessive fat synthesis,reduced metabolism,and decreased transport capacity,will cause the risk of a variety of diseases such as non-alcoholic fatty liver disease,liver fibrosis and cirrhosis,cholestasis,and even liver cell carcinoma rising rapidly.Liver is also closely related to the induction of other metabolic diseases.Recent studies have declared that glycine-N-methyltransferase(GNMT)in the liver acts as a key enzyme that regulates the conversion of S-adenosylmethionine(SAM)to S-adenosyl homocysteine(SAH),which can change the in-body level of SAM and then regulates the body’s methylation status.GNMT can also alter the expression of fat metabolism and transport related genes,as well as the activity of oxidative respiratory complexⅡto regulate fat content and reduce the occurrence and further development of diseases.This review describes the regulatory effects of GNMT on lipid metabolism,glucose metabolism,and oxidative stress in the liver.The therapeutic effects of GNMT in a variety of liver diseases are also discussed.This article can lay a solid theoretical foundation for future treatment methods and targets aim to GNMT.

关 键 词：甘氨酸-N-甲基转移酶(GNMT) 脂代谢 甲基循环 肝脏疾病 

分 类 号：S18[农业科学—农业基础科学]