Thornalley P J
Department of Biological and Chemical Sciences, University of Essex, Colchester, UK.
Chem Biol Interact. 1998 Apr 24;111-112:137-51. doi: 10.1016/s0009-2797(97)00157-9.
The glyoxalase system is a metabolic pathway that catalyses the detoxification of alpha-oxoaldehydes RCOCHO to corresponding aldonic acids RCH(OH)CO2H. It thereby protects cells from alpha-oxoaldehyde-mediated formation of advanced glycation endproducts (AGEs). It is comprised of two enzymes, glyoxalase I and glyoxalase II, and a catalytic amount of reduced glutathione (GSH) as cofactor. It is present in the cytosol of cells of mammals and most micro-organisms. Physiological substrates of the glyoxalase system are: glyoxal--formed from lipid peroxidation and glycation reactions, methylglyoxal--formed from triosephosphates, ketone body metabolism and threonine catabolism, and 4,5-dioxovalerate--formed from 5-aminolevulinate and alpha-ketoglutarate. alpha-Oxoaldehydes react with guanyl residues in DNA and RNA, and with cysteine, lysine and arginine residues in proteins. The modification of DNA induces mutagenesis and apoptosis. The modification of proteins leads to protein degradation and activation of a cytokine-mediated immune response.
乙二醛酶系统是一种代谢途径，可催化α-氧代醛RCOCHO解毒生成相应的醛糖酸RCH(OH)CO2H。因此，它可保护细胞免受α-氧代醛介导的晚期糖基化终产物（AGEs）的形成。它由两种酶，即乙二醛酶I和乙二醛酶II，以及催化量的还原型谷胱甘肽（GSH）作为辅因子组成。它存在于哺乳动物和大多数微生物细胞的胞质溶胶中。乙二醛酶系统的生理底物有：由脂质过氧化和糖基化反应形成的乙二醛、由磷酸丙糖、酮体代谢和苏氨酸分解代谢形成的甲基乙二醛，以及由5-氨基乙酰丙酸和α-酮戊二酸形成的4,5-二氧戊酸。α-氧代醛与DNA和RNA中的鸟苷残基以及蛋白质中的半胱氨酸、赖氨酸和精氨酸残基发生反应。DNA的修饰会诱导诱变和细胞凋亡。蛋白质的修饰会导致蛋白质降解并激活细胞因子介导的免疫反应。
