Maessen Dionne E M, Stehouwer Coen D A, Schalkwijk Casper G
*Department of Internal Medicine, CARIM School for Cardiovascular Diseases, Maastricht University Medical Centre, Peter Debeyelaan 25, P.O. Box 5800, 6202 AZ Maastricht, The Netherlands.
Clin Sci (Lond). 2015 Jun;128(12):839-61. doi: 10.1042/CS20140683.
The formation and accumulation of advanced glycation endproducts (AGEs) are related to diabetes and other age-related diseases. Methylglyoxal (MGO), a highly reactive dicarbonyl compound, is the major precursor in the formation of AGEs. MGO is mainly formed as a byproduct of glycolysis. Under physiological circumstances, MGO is detoxified by the glyoxalase system into D-lactate, with glyoxalase I (GLO1) as the key enzyme in the anti-glycation defence. New insights indicate that increased levels of MGO and the major MGO-derived AGE, methylglyoxal-derived hydroimidazolone 1 (MG-H1), and dysfunctioning of the glyoxalase system are linked to several age-related health problems, such as diabetes, cardiovascular disease, cancer and disorders of the central nervous system. The present review summarizes the mechanisms through which MGO is formed, its detoxification by the glyoxalase system and its effect on biochemical pathways in relation to the development of age-related diseases. Although several scavengers of MGO have been developed over the years, therapies to treat MGO-associated complications are not yet available for application in clinical practice. Small bioactive inducers of GLO1 can potentially form the basis for new treatment strategies for age-related disorders in which MGO plays a pivotal role.
晚期糖基化终产物（AGEs）的形成和积累与糖尿病及其他与年龄相关的疾病有关。甲基乙二醛（MGO）是一种高反应性二羰基化合物，是AGEs形成的主要前体。MGO主要作为糖酵解的副产物形成。在生理情况下，MGO通过乙二醛酶系统解毒为D-乳酸，其中乙二醛酶I（GLO1）是抗糖基化防御中的关键酶。新的研究表明，MGO水平升高、主要的MGO衍生AGEs即甲基乙二醛衍生的氢咪唑酮1（MG-H1）以及乙二醛酶系统功能失调与多种与年龄相关的健康问题有关，如糖尿病、心血管疾病、癌症和中枢神经系统疾病。本综述总结了MGO的形成机制、其通过乙二醛酶系统的解毒过程以及其对与年龄相关疾病发展相关生化途径的影响。尽管多年来已经开发了几种MGO清除剂，但用于治疗与MGO相关并发症的疗法尚未应用于临床实践。GLO1的小生物活性诱导剂可能为以MGO起关键作用的与年龄相关疾病的新治疗策略奠定基础。
