Nagahara Noriyuki, Sawada Nori
Department of Environmental Medicine, Nippon Medical School, Tokyo 113-8602, Japan.
Curr Med Chem. 2006;13(10):1219-30. doi: 10.2174/092986706776360914.
The conversion of cysteine to 3-sulfino-alanine is a major pathway in cysteine catabolism. Cysteine dioxygenase catalyzes the reaction and dietary intake of the essential amino acid methionine and the semi-essential amino acid cysteine increases the level of this enzyme by suppressing enzyme degradation via polyubiquitination. The production of cellular antioxidants such as glutathione, thioredoxin, and their families is important in cysteine metabolism, and these cellular antioxidants have critical roles in the maintenance of the cellular redox status. The mercaptopyruvate pathway, in which cysteine or aspartate transaminase catalyzes the transamination from cysteine to 3-mercaptopyruvate and then 3-mercaptopyruvate sulfurtransferase catalyzes the transsulfuration from 3-mercaptopyruvate to pyruvate, also contributes to maintain the cellular redox. 3-Mercaptopyruvate sulfurtransferase serves as an antioxidant protein: when the enzyme is exposed to stoichiometric amounts of the oxidant hydrogen peroxide, it is inhibited via the formation of low redox sulfenate at the catalytic site cysteine. On the other hand, activity is restored by the reductant dithiothreitol or reduced thioredoxin. 3-Mercaptopyruvate sulfurtransferase also detoxifies cyanide via transsulfuration from a stable persulfide at the catalytic site cysteine, a reaction intermediate, suggesting that cyanide detoxification is not necessarily an enzymatic reaction. Furthermore, a congenital defect of the enzyme causes mercaptolactate-cysteine disulfiduria associated with or without mental retardation, although the pathogenesis remains unclear. These facts suggest that 3-mercaptopyruvate sulfurtransferase has physiologic roles as an antioxidant and a cyanide antidote; is essential for neural function, and participates in cysteine degradation.
半胱氨酸转化为3-亚磺基丙氨酸是半胱氨酸分解代谢的主要途径。半胱氨酸双加氧酶催化该反应，必需氨基酸蛋氨酸和半必需氨基酸半胱氨酸的膳食摄入通过抑制酶的多聚泛素化降解来提高该酶的水平。细胞抗氧化剂如谷胱甘肽、硫氧还蛋白及其家族的产生在半胱氨酸代谢中很重要，这些细胞抗氧化剂在维持细胞氧化还原状态中起关键作用。巯基丙酮酸途径，其中半胱氨酸或天冬氨酸转氨酶催化半胱氨酸转氨生成3-巯基丙酮酸，然后3-巯基丙酮酸硫转移酶催化3-巯基丙酮酸转硫生成丙酮酸，也有助于维持细胞氧化还原状态。3-巯基丙酮酸硫转移酶作为一种抗氧化蛋白：当该酶暴露于化学计量的氧化剂过氧化氢时，它会通过在催化位点半胱氨酸处形成低氧化还原状态的亚磺酸盐而被抑制。另一方面，还原剂二硫苏糖醇或还原型硫氧还蛋白可恢复其活性。3-巯基丙酮酸硫转移酶还通过催化位点半胱氨酸处的稳定过硫化物（一种反应中间体）进行转硫作用来解毒氰化物，这表明氰化物解毒不一定是酶促反应。此外，该酶的先天性缺陷会导致伴有或不伴有智力迟钝的巯基乳酸-半胱氨酸二硫化物尿症，尽管其发病机制尚不清楚。这些事实表明，3-巯基丙酮酸硫转移酶具有作为抗氧化剂和氰化物解毒剂的生理作用；对神经功能至关重要，并参与半胱氨酸的降解。
