High homocysteine levels in Alzheimer’s disease (AD) result from low activity of the trans-sulfuration pathway. Glutathione levels are also low in AD. L-cysteine is required for the synthesis of glutathione. The synthesis of coenzyme A (CoA) requires L-cysteine, which is synthesized via the trans-sulfuration pathway. CoA is required for the synthesis of acetylcholine and appropriate cholinergic neurotransmission. L-cysteine is required for the synthesis of molybdenum-containing proteins. Sulfite oxidase (SUOX), which is a molybdenum-containing protein, could be dysregulated in AD. SUOX detoxifies the sulfites. Glutaminergic neurotransmission could be dysregulated in AD due to low levels of SUOX and high levels of sulfites. L-cysteine provides sulfur for iron-sulfur clusters. Oxidative phosphorylation (OXPHOS) is heavily dependent on iron-sulfur proteins. The decrease in OXPHOS seen in AD could be due to dysregulations of the trans-sulfuration pathway. There is a decrease in aconitase 1 (ACO1) in AD. ACO1 is an iron-sulfur enzyme in the citric acid cycle that upon loss of an iron-sulfur cluster converts to iron regulatory protein 1 (IRP1). With the dysregulation of iron-sulfur cluster formation ACO1 will convert to IRP1 which will decrease the 2-oxglutarate synthesis dysregulating the citric acid cycle and also dysregulating iron metabolism. Selenomethionine is also metabolized by the trans-sulfuration pathway. With the low activity of the trans-sulfuration pathway in AD selenoproteins will be dysregulated in AD. Dysregulation of selenoproteins could lead to oxidant stress in AD. In this article, we propose a novel treatment for AD that addresses dysregulations resulting from low activity of the trans-sulfuration pathway and low L-cysteine.

中文翻译：

---

阿尔茨海默病的疾病改善疗法：关注反式硫化途径

阿尔茨海默病 (AD) 中的高同型半胱氨酸水平是由反式硫化途径的低活性引起的。AD中的谷胱甘肽水平也很低。L-半胱氨酸是谷胱甘肽合成所必需的。辅酶 A (CoA) 的合成需要通过反式硫化途径合成的 L-半胱氨酸。CoA 是合成乙酰胆碱和适当的胆碱能神经传递所必需的。L-半胱氨酸是合成含钼蛋白质所必需的。亚硫酸氧化酶 (SUOX) 是一种含钼蛋白质，在 AD 中可能会失调。SUOX 解毒亚硫酸盐。由于低水平的 SUOX 和高水平的亚硫酸盐，AD 中的谷氨酰胺能神经传递可能失调。L-半胱氨酸为铁硫簇提供硫。氧化磷酸化 (OXPHOS) 严重依赖于铁硫蛋白。AD 中 OXPHOS 的减少可能是由于反式硫化途径的失调。AD 中乌头酸酶 1 (ACO1) 减少。ACO1 是柠檬酸循环中的一种铁硫酶，当铁硫簇丢失时，它会转化为铁调节蛋白 1 (IRP1)。随着铁硫簇形成的失调，ACO1 将转化为 IRP1，这将减少 2-草酸合成，从而失调柠檬酸循环，也失调铁代谢。硒代蛋氨酸也通过反式硫化途径代谢。由于 AD 中反式硫化途径的低活性，硒蛋白在 AD 中会失调。硒蛋白的失调可能导致 AD 中的氧化应激。在本文中，