MECHANISM OF ADENOSINE-TRIPHOSPHATE DEPLETION IN LIVER AFTER A LOAD OF FRUCTOSE - KINETIC STUDY OF LIVER ADENYLATE DEAMINASE
MECHANISM OF ADENOSINE-TRIPHOSPHATE DEPLETION IN LIVER AFTER A LOAD OF FRUCTOSE - KINETIC STUDY OF LIVER ADENYLATE DEAMINASE
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DOI：
10.1042/bj1620601
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发表时间：
1977-01-01
影响因子：
4.1
通讯作者：
HERS, HG
中科院分区：
文献类型：
--
作者：
VANDENBERGHE, G;BRONFMAN, M;HERS, HG
1.在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30秒时观察到的第一个变化是Pi浓度的降低和果糖1-磷酸的同时积累。ATP和GTP浓度的下降进行得更慢。仅在1 min后检测到IMP浓度增加，因此不能认为是1-磷酸果糖蓄积的原因。2.为了解释在果糖负荷后发生的腺嘌呤核苷酸分解的暂时爆发，在底物的生理浓度（0.2mM）下重新研究了来自大鼠肝脏的AMP脱氨酶（EC3.5.4.6）的动力学。为此，开发了一种新的放射化学测定程序。在0. 2 mM-AMP浓度下，可测得较低的活性，5 mM-Pi可抑制90%以上的活性。ATP（3 MM）使酶活性增加200倍以上。单独的Pi对ATP激活酶无影响，而0. 5 mM-GTP对ATP激活酶有60%的抑制作用。两种抑制剂在其生理浓度下的组合效果达到95%。3.有人提出，腺嘌呤核苷酸的快速降解后发生的负载的果糖是由两个抑制剂，Pi和GTP的浓度下降，很快抵消了ATP的浓度下降。4.肝AMP脱氨酶的一些动力学参数根据Monod，Wyman和Changeux（1965）（J. Mol. Biol. 12，88-118）。
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).