Kohn M C, Garfinkel D
Am J Physiol. 1977 Apr;232(4):H386-93. doi: 10.1152/ajpheart.1977.232.4.H386.
A model is proposed for the partial depletion of the adenine nucleotide pool in the ischemic perfused rat heart which involves seven enzymes: adenylate cyclase, 3',5'-cyclic AMP phosphodiesterase, 5'-nucleotidase, adenosine kinase, adenosine deaminase, purine nucleoside phosphorylase, and inorganic pyrophosphatase. The computer implementation of this model is in terms of rate laws, several of which were obtained by a systematic least-squares fitting procedure. Depletion of the adenine nucleotide pool is initiated by the release of endogenous noradrenaline into the interstitial fluid, which results from a fall in tissue PO2, and the subsequent activation of adenylate cyclase. In this model the substrate for 5'-nucleotidase is a membrane-bound AMP pool formed by hydrolysis of extracellular fluid and functions as a vasodilator; excess adenosine is incorporated into the tissue by a "permease" with Michaelis-Menten kinetics and converted to AMP, inosine, and hypoxanthine. Alternative mechanisms, such as the deamination of AMP by adenylate deaminase and conversion of AMP to adenine by AMP pyrophosphorylase, were rejected primarily on qualitative biochemical grounds.
提出了一个关于缺血灌注大鼠心脏中腺嘌呤核苷酸池部分耗竭的模型，该模型涉及七种酶：腺苷酸环化酶、3',5'-环磷酸腺苷磷酸二酯酶、5'-核苷酸酶、腺苷激酶、腺苷脱氨酶、嘌呤核苷磷酸化酶和无机焦磷酸酶。该模型的计算机实现基于速率定律，其中一些速率定律是通过系统的最小二乘法拟合程序获得的。腺嘌呤核苷酸池的耗竭是由内源性去甲肾上腺素释放到细胞间液中引发的，这是由于组织PO2下降以及随后腺苷酸环化酶的激活所致。在该模型中，5'-核苷酸酶的底物是由细胞外液水解形成的膜结合AMP池，其作为血管舒张剂起作用；过量的腺苷通过具有米氏动力学的“通透酶”被纳入组织，并转化为AMP、肌苷和次黄嘌呤。主要基于定性生化依据排除了其他机制，如腺苷酸脱氨酶对AMP的脱氨作用以及AMP焦磷酸化酶将AMP转化为腺嘌呤的作用。
