Loomis W F, Thomas S R
J Biol Chem. 1976 Oct 25;251(20):6252-8.
The metabolic network leading to accumulation of cellulose, trehalose, and mucopolysaccharide during development of Dictyostelium discoideum was simulated on a computer. The program consists of a metabolic map, the measured specific activity of the enzymes involved at each stage in development, and the substrate and inhibitor affinities. The Km values of four enzymes, amylase, UDP-galactose polysaccharide transferase, UDP-galactose epimerase, and cellulose synthetase, were determined for this study. At each iteration (1 min) during the period simulated (1500 min), the in vivo activity was calculated for each enzyme using Michaelis-Menten equations and new values for metabolites and end products were generated. The computed values for the concentration of both metabolites and polysaccharides were in close agreement with the measured values at all stages of development. We conclude that the in vitro measured values correlate well with the measured in vivo rates when treated in this manner. The program was modified to simulate the alterations in carbohydrate metabolism which might be expected in mutant strains with reduced activity of various enzymes. Trehalose was found to overaccumulate when either the peak value of the developmentally controlled increase in the specific activity of UDPGlc pyrophosphorylase was reduced. Trehalose accumulation was decreased in simulations of mutants lacking glycogen phosphorylase or glycogen synthetase. The interaction of these metabolic pathways is discussed.
利用计算机模拟了盘基网柄菌发育过程中导致纤维素、海藻糖和粘多糖积累的代谢网络。该程序由代谢图谱、发育各阶段所涉及酶的实测比活性以及底物和抑制剂亲和力组成。本研究测定了淀粉酶、UDP-半乳糖多糖转移酶、UDP-半乳糖差向异构酶和纤维素合成酶这四种酶的Km值。在模拟期（1500分钟）的每次迭代（1分钟）中，使用米氏方程计算每种酶的体内活性，并生成代谢物和终产物的新值。代谢物和多糖浓度的计算值与发育各阶段的测量值密切吻合。我们得出结论，以这种方式处理时，体外测量值与体内测量速率具有良好的相关性。对该程序进行了修改，以模拟各种酶活性降低的突变菌株中可能预期的碳水化合物代谢变化。当UDPGlc焦磷酸化酶比活性的发育控制增加峰值降低时，发现海藻糖过度积累。在缺乏糖原磷酸化酶或糖原合成酶的突变体模拟中，海藻糖积累减少。讨论了这些代谢途径的相互作用。
