應用派翠網技術建構與分析疾病相關的甲硫酸胺及葉酸代謝網路

Construction and Analysis of Disease-Related Methionine and Folate Cycles with Petri Net

心血管疾病的危險因子之一為同半胱胺酸(Homocysteine)濃度過高，而同半胱胺酸為甲硫酸胺(Methionine)循環中的產物。當甲硫酸胺網路代謝過程發生異常時，即有可能使得基質濃度不穩定，產生嚴重疾病。本研究的目的，在於利用派翠網(Petri Net)技術，透過傳統的文獻資料，於電腦軟體上建構甲硫酸胺及葉酸(folate)代謝網路，透過實際模擬結果後的資料分析，了解酵素功能在代謝網路中的影響；基質的濃度變化與預測疾病，提供除了傳統實驗室檢測之外的應用。實驗設計從蒐集代謝網路的資料開始，將基質與酵素的關係轉換成生物途徑模擬軟體上的元件，設定動力式與變數項，給定觸發起始值，確認實驗數據。藉由模擬酵素功能異常與甲硫酸胺攝取增減量，進而分析結果及預測造成疾病之影響。循環中的酵素或基質濃度偏離正常標準值，會造成不同病症與疾病的情況發生。研究結果顯示，當缺乏甲硫酸胺核苦轉移酵素(Methionine Adenosyl Transferase)時，甲硫酸胺會快速累積，導致高甲硫胺酸血症(Hypermethioninemia)。若當葉酸的濃度不足時，會使得同半胱胺酸的濃度上升，血管內的管壁增厚，容易阻塞，將成為很多疾病的危險因子，例如心血管疾病、中風、癡呆等。補充葉酸會造成甲硫酸胺的濃度小幅上升、S-腺嘌呤核苷甲硫酸胺(S-Adenosyl-Methionine)大幅度上升與同半胱胺酸濃度下降，減低罹患相關疾病的風險。

High concentration of homocysteine in blood is one of the most dangerous risk factors of cardiovascular disease. The homocysteine is a metabolite produced in the methionine cycle. If enzyme activities are unusual in the methionine cycle, the concentration of metabolite will be influenced, and therefore cause some critical diseases. The purpose of this paper is to construct and analyze methionine and folate cycles using Petri net. By studying the effects of the enzyme activities on the concentration of metabolites and the relationships between metabolite concentration and the human diseases, we can predict the possible causes of diseases. In other words, our model will serve as a prediction system beyond the traditional experimental results. Previous studies showed that the malfunction of methionine adenosyl transferase (MAT) will rapidly increase the concentration of methionine which then causes Hypermethioninemia. Lacking of folate in the human body, the concentration of homocysteine will accumulate in the blood vessels and eventually block the vessels. It increases the risk of getting Cardiovascular Disease, stroke, dementia and many other diseases. In this study, both methionine and folate cycles were constructed using hybrid functional Petri net techniques. The simulation results showed that by providing enough folate, the concentration of methionine and S- Adenosyl- Methionine (AdoMet) will be increased which then cause the decrease of the concentration of homocysteine. The results may provide a method to decrease the probability of getting related diseases. In the future, we intend to apply this computer technique to other important biological cycles in the human body. Hopefully, it can benefit the improvement of human health.