- 學位論文
人體肝臟細胞之代謝模式建立與通量分析
Establishment of metabolic mode and analysis of fluxes on human hepatocyte
摘要
肝臟為人體重要代謝器官，其中肝細胞(Hepatocyte)作用的功能包括蛋白質與脂質代謝、合成血漿蛋白與膽汁、儲存糖原等重要的生理機制。而其粒線體(mitochondria)為肝細胞經三羧酸循環(Tricarboxylic acid cycle)與呼吸鏈生成三磷酸腺苷(Adenosine triphosphate，ATP)之主要場所，提供細胞所需之能量以維持肝細胞正常生理運作。 本研究為利用人類肝細胞代謝網路模型HepatoNet1，在肝細胞攝取必須營養基質(例:水、氧氣、必需胺基酸與脂肪酸、維生素)與排出不可再降解之肝代謝終端產物(例:二氧化碳、尿素)之情況，並執行降解低密度脂蛋白(Low-density lipoprotein，LDL)、高密度脂蛋白(High-density lipoprotein，HDL)與生成甘氨膽酸(glycocholic acid)等生理功能，使用通量均衡分析方法(Flux balance analysis, FBA)模擬人類肝細胞受干擾狀態下最小化內部通量，得到之穩態通量分佈中與正常狀況下有明顯變化的通量比較，並找出使正常生理代謝功能無法運作之剔除通量與對應之酵素缺乏症(Enzyme Deficiencies)。
並列摘要
Liver is one of the important human organs in metabolism. Hepatocytes perform most of physiological liver function including metabolize of proteins and lipids, synthesis of plasma proteins and bile, storage of glycogen. The mitochondria of hepatocytes is main place to product ATP through TCA cycle and electron transfer chain to provide the require energy of human body This research use the human hepatocyte metabolic network HepatoNet1 to accomplish physiological objective in degradation LDL, HDL and formation of glycocholic acid under the condition of uptaking importable nutrients (e.q. oxygen, water, essential amino and fatty acids, vitamins) and secretion non-degradable end products of hepatic metabolism, for example,CO2 and urea. We use Flux balance analysis to simulate at the situation of perturbations and get flux distribution of network at steady state. We compare the result of perturbations to the fluxes of normal condition, then getting the fluxes with significant difference, therefore finding out the reactions which could not carry flux would cause some failures of physiological functions and the corresponding Enzyme Deficiencies.