在許多生物科技與環保科技中，如胰島素之製造、人體血液內葡萄糖代謝量之判定、酵素對污染物進行共價鍵結之環保應用上等，都與系統代謝息息相關。截至目前為止，這方面研究工作大都以實驗統計試誤法為主，往復調整實驗步驟以使代謝量符合預定需求，然而目前尚無完整理論模型及模擬流程可供應用，而電腦化特性分析工具亦正是目前代謝系統研發與應用所缺乏的。因此為了能夠快速化及精確化地掌握代謝特性並提高系統的代謝效率及分析時效，有必要建構一套完備且可定量分析的代謝理論模型及模擬程序。因此本研究以人體血糖代謝系統為例，模擬葡萄糖在人體血液中之反應機制，建構一套完整的代謝理論、模擬程序及電腦化的估算系統。

本研究以微觀分子力學模型為基礎，探討代謝反應過程之反應機制與人體血糖代謝疾病之診斷及給定代謝量下酵素最低成本之求取等應用為主題，並以此建構一套完整的代謝系統理論模型。本文首先利用分子間作用力場估算溶質所需克服之活化能及反應位能曲面，利用能量最小化法以估算反應態、產物態及反應路徑。接著以自由能微擾法推估自由能變化及代謝反應常數，以微觀角度分析系統代謝反應之物理規則。再根據反應常數、反應路徑及Michaelis-Menten來建構動態反應方程以求解系統之代謝量及通量並推估相關代謝控制係數，以完成代謝系統反應過程中之定量分析準則。最後利用本理論模型，以反應代謝量與疾病臨界值判斷人體血液內葡萄糖代謝異常所引發之代謝性疾病及利用代謝控制理論推估反應所需酵素最低成本等應用上。

由本文所建立之分子間作用力場推估代謝反應常數並利用反應常數、反應路徑及Michaelis-Menten方程建構動態方程推估代謝量及通量，所得結果與文獻實驗資料相互比對之結果，平均誤差皆落於10%內，證實本文所提之理論模型確實可行。反應常數，代謝量及通量之取得若經由本文之理論模型進行推估可取代傳統繁雜的實驗方法及經驗值法。此外本研究所建構之模型應用於人體血糖代謝性疾病之診斷及代謝反應酵素最低成本之求取上，證實本理論模型之實用性，未來更可將該套理論推廣於其他各種生物技術，醱酵工程等應用。

The biology and environment process technology are related to metabolism closely, example of the manufacture of insulin, the irregular metabolism of blood sugar estimated in human body, the enzyme bond with pollutants covalently for environment protection. Traditionally, the research about metabolic engeneering is done by using trial-error method and changing influentical factor, but this will make the metabolic process multifarious and metabolic efficiency won’t be promoted. In oreder to promoted the efficiency of the metabolic system and characterize the metabolic reaction mechanism, this project will finally estabolish a comprehensive and computational simulation process for metabolic system.

The paper will establish a metabolic kinetic and thermodynamic model that can be applied to the metabolite measurement for diagnosing the disease about blood sugar in human body and economize the use of enzyme for metabolic reaction. First, the potential energy surface is established by molecular forcefield and the reaction pathway is obtained by minimum energy method. Secondly, the free energy perturbation method will be used to estimate the key metabolic parameters. Finally, the amount of metabolite and metabolic flux are obtained by solving the dynamics reaction equations. The comprehensive model will integrate all relative parameters and discuss the physical meaning and kinetics behaviors. Then establish the metabolic pathway algorithm to estimate the quanity of metabolite for characterize the reaction mechanism and analytical rule. The results will then be further verified by experimental data.

Good agreements between the computed solutions and experimental data in the literature indicate the proposed theory is feasible. The key metabolic parameter can be obtained from examples presented in the paper without multifarious experiment steps. In the future, the theory can be popularized to other application, such as fermentation engineering, bio-examination, etc.

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