Construction and Exploration of the Complete Disease-Related Methionine Cycles with Hybrid Functional Petri Net

• Main Authors: Siang-hao Lee, 李祥豪
• Other Authors: Austin H. Chen
• Format: Others
• Language: zh-TW
• Online Access: http://ndltd.ncl.edu.tw/handle/46490088803971962225

碩士 === 慈濟大學 === 醫學資訊研究所 === 96 === One of the major factors to regulate human health is the metabolism of human body. Due to the complexity of human metabolism, research in this area remains a major challenge. Methionine, an essential amino acid, and its derivatives play significant roles in the regulation of human body, such as methyltransferase, transsulfuration and cell division. It has been proven that malfunctions in the methionine cycle lead to many severe diseases. If the methionine cycle is not functioning properly or is temporarily blocked, the effect manifests itself as cardiovascular disease, liver disease, Alzheimer’s disease, Down syndrome, neural tube defects, and various cancers. In this paper, we have developed and constructed the complete methionine cycle based on hybrid functional Petri net techniques. It allowed us to build the model in a single graphical platform and run the dynamic simulation for all reactions simultaneously. We then used this complete model to further explore many new insights, especially the relationship between components of this cycle and disease. Firstly, we discuss the effect of various enzymes when they loss the functions in the complete methionine cycle. Due to gene deficiency, nutrition element ingested or metabolism abnormality, many enzymes will loss their functions which results in many diseases. In this study, we discuss the effect of several enzymes occurred in the complete methionine cycle. Among the enzymes are methionine adenosyl transferase I (MATI), methionine adenosyl transferase III (MATIII), S-adenosyl- methionine- dependent methyltransferases (SM), glycine N-methyltransferase (GNMT), S-adenosylhomocysteine hydrolase (AH), cystathionine bsynthase (CBS), methionine synthase (MS) and betaine:homocysteine methyltransferase (BHMT). Secondly, we discuss the effect of substrates concentration on various diseases. Three major substrates are studied in this paper, including methionine, homocysteine and folate pool.