The mechanism of adenosine triphosphate depletion in the liver after a load of fructose. A kinetic study of liver adenylate deaminase.
The mechanism of adenosine triphosphate depletion in the liver after a load of fructose. A kinetic study of liver adenylate deaminase.
复制标题
果糖负荷后肝脏中三磷酸腺苷消耗的机制。
作者：
G. van den Berghe;M. Bronfman;R. Vanneste;H. Hers
1. 在给小鼠静脉注射果糖后的最初几分钟内，测量了几种核苷酸和代谢物的肝脏浓度。在30s时观察到的第一个变化是Pi浓度下降，同时果糖1-磷酸积累。ATP和GTP浓度的下降速度较慢。仅在1分钟后检测到IMP浓度的增加，因此不能认为是果糖1-磷酸积累的原因。2. 为了解释果糖负荷后腺嘌呤核苷酸分解的暂时爆发，在生理（0.2 mM）底物浓度下重新研究了大鼠肝脏AMP脱氨酶（EC 3.5.4.6）的动力学。为此，开发了一种新的放射化学分析程序。在0.2mM-AMP时，活性较低，5mM-Pi抑制90%以上。ATP （3MM）使酶活性增加200倍以上。单独使用Pi对atp活化酶没有影响，而0.5mM-GTP对atp活化酶有60%的抑制作用。两种抑制剂在其生理浓度下的联合效应达到95%。3. 有人提出，在负荷果糖后发生的腺嘌呤核苷酸的快速降解是由Pi和GTP这两种抑制剂浓度的降低引起的，很快被ATP浓度的降低所抵消。4. 肝脏AMP脱氨酶的一些动力学参数是根据Monod， Wyman & Changeux (1965) （J. Mol. Biol. 12,88 -118）的协同过渡理论计算的。
1. The hepatic concentration of several nucleotides and metabolites was measured during the first few minutes after an intravenous load of fructose to mice. The first changes, observed at 30s, were a decrease in the concentration of Pi and a simultaneous accumulation of fructose 1-phosphate. The decrease in the concentrations of ATP and GTP proceeded more slowly. An increase in the concentration of IMP was detected only after 1 min and could therefore not be considered to be the cause of the accumulation of fructose 1-phosphate. 2. To explain the temporary burst of adenine nucleotide breakdown that occurs after a load of fructose, the kinetics of AMP deaminase (EC 3.5.4.6) from rat liver were reinvestigated at physiological (0.2 mM) concentration of substrate. For this purpose, a new radiochemical-assay procedure was developed. At 0.2mM-AMP a low activity could be measured, which was more than 90% inhibited by 5mM-Pi. ATP (3MM) increased the enzyme activity over 200-fold. Pi alone did not influence the ATP-activated enzyme, but 0.5mM-GTP caused a 60% inhibition. The combined effect of both inhibitors at their physiological concentrations reached 95%. 3. It is proposed that the rapid degradation of adenine nucleotides that occurs after a load of fructose is caused by a decrease in the concentration of both inhibitors, Pi and GTP, soon counteracted by the decrease in the concentration of ATP. 4. Some of the kinetic parameters of liver AMP deaminase were computed in terms of the concerted transition theory of Monod, Wyman & Changeux (1965) (J. Mol. Biol. 12, 88-118).