穀胱甘肽代謝途徑之設計與分析

Design and Analysis of the Glutathione Metabolic Pathway

趙俊傑(Chun-Chieh Chao)

指導教授 ： 王逢盛

國立中正大學/工學院/化學工程學系/碩士(2014年)

摘要

穀胱甘肽(Glutathione, GSH)，是由半胱氨酸(Cysteine)，谷氨酸(Glutamic Acid)和甘氨酸(Glycine)組成的三肽。穀胱甘肽(Glutathione, GSH)的主要功能在於細胞內的抗氧化防禦，包括對抗活性氧化物質（Reactive Oxygen Species, ROS）。而穀胱甘肽與氧化型穀胱甘肽的比例在調節細胞氧化還原狀態上扮演著重要的角色。
本研究設定三種情況當為目標，第一種為長期服用對乙醯氨基酚( paracetamol )後，利用最適化方法找尋如何將對乙酰氨基酚與穀胱甘肽結合物濃度上升1074倍回復的複合藥方設計，第二種為當穀胱甘肽合成酶( Glutathione systhetase )表現量只有原本55%時造成焦谷氨酸( 5-oxoproline )濃度上升1.33倍，利用最適化方法使焦谷氨酸濃度回復成正常值之新藥物設計，第三種為人體中穀胱甘肽以及氧化型穀胱甘肽的比例做為目標，找尋因異常之目標造成比例下降至0.88以及利用最適化方法調控目標使比例回復成基礎值的0.8倍至1.2倍之間，並以回復目標當作新藥物設計。

關鍵字

穀胱甘肽 ； 靈敏度分析 ； 最佳化方法 ； 氧化型穀胱甘肽

並列摘要

Reduced glutathione (GSH), a ubiquitous tripeptide thiol, is a vital intracellular and extracellular protective antioxidant, which plays an important of key and crucial roles in detoxifying certain xenobiotics and heavy metals, as well as other functions.
In this study, we set three targets. First, long-term use of acetaminophen caused acetaminophen and glutathione conjugates rose 1074 times. We used optimization method to recovery acetaminophen and glutathione conjugates. Second, Glutathione synthetase only express 55% will cause 5-oxoproline concentration rise 1.33 times. We not only used optimization methods to let 5-oxoproline revert to normal but also designed of new drugs. Third, we selected the proportion of the glutathione and oxidized glutathione as our target, in order to find targets which caused ratio decrease. Final, we not only used optimization method to make proportion revert to the basal value between 0.8 times to 1.2 times but also designed of new drugs.

並列關鍵字

Glutathione ； Sensitivity analysis ； Optimization method ； Glutathione disulfide

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