Interaction of metal(III)-adenosine 5'-triphosphate complexes with yeast hexokinase.
Interaction of metal(III)-adenosine 5'-triphosphate complexes with yeast hexokinase.
复制标题
金属 (III)-腺苷 5-三磷酸复合物与酵母己糖激酶的相互作用。
DOI：
10.1021/bi00555a003
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发表时间：
1980
期刊：
影响因子：
2.9
通讯作者：
Cleland,WW
中科院分区：
文献类型：
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作者：
Viola,RE;Morrison,JF;Cleland,WW
罗纳德E. Viola，1 John F.莫里森和WW克莱兰 ** 摘要：在葡萄糖存在下，酵母己糖激酶被所有在中性pH下不水解的MmATP（=金属）络合物特异性地强烈抑制，只要金属的离子半径小于0.89 μ m。K值从微摩尔范围（例如，pH 7时A1 ATP为0.16 µ）到LuATP低至13 nM不等。与葡萄糖和果糖，紧密结合的复合物也显示可逆的，缓慢的结合行为，但与poorsubstrates，很少或没有变化的抑制常数随时间的推移进行观察。柠檬酸盐作为己糖激酶反应的活化剂的动力学是一致的。有证据表明，酵母己糖激酶在pH 7下显示非线性动力学，但在pH 8下不显示。从较快的初始速率到较慢的稳态速率观察到缓慢的相互转化（Shill和Neet，1971），并且这种相互转化被某些阴离子的存在所阻止（Alfrew和Rose，1971），其中柠檬酸盐是最有效的。据推测，这种缓慢的瞬时过程和阴离子的激活是酵母己糖激酶的调节特性，起着生理作用（Shill & Neet，1975; Peters & Neet，1977）。然而，Womack和Colowick（1979）最近表明，在ATP的商业制剂中存在不同量的污染性三价铝离子，并且酵母己糖激酶在pH 7或更低时（但在pH 8时不）被铝-ATP复合物抑制。他们认为，柠檬酸盐的激活是通过与柠檬酸盐螯合从ATP复合物中除去铝的结果。在本报告中，我们将表明，在中性pH下与ATP形成稳定络合物的三价金属是酵母己糖激酶的非常紧密的抑制剂，并且在pH 7下，
Ronald E. Viola, 1 John F. Morrison, and WW Cleland** abstract: In the presence of glucose, yeast hexokinase is specifically and strongly inhibited by all MmATP (= metal) complexes that do not hydrolyze at neutralpH, as long as the ionic radius of the metal is less than 0.89 Á. K¡ values vary from the micromolar range (0.16 µ for A1ATP at pH 7, for example) to as low as 13 nM for LuATP. With glucose and fructose, the tightly bound complexes also show reversible, slow binding behavior, but with poorsubstrates, little or no change in inhibition constant with time is observed. Thekinetics of citrate as an activator of the hexokinase reaction are consistentI^ evious studies have shown that yeast hexokinase displays nonlinear kinetics at pH 7, but not at pH 8. A slow interconversion is observed from a faster initial rate to a slower steady-state rate (Shill & Neet, 1971), and this interconversion is preventedby the presence of certain anions (Kosow & Rose, 1971), with citrate being the most efficient. It has been postulated that this slow transient process andthe activation by anions are regulatory properties of yeast hexokinase that play a physiological role (Shill & Neet, 1975; Peters & Neet, 1977). However, Womack & Colowick (1979) have recently shown the presence of variable amounts of contaminating trivalent aluminum ion in commercial preparations of ATP, and that yeast hexokinase is inhibited by an aluminum-ATP complex at pH 7 or below (but not at pH 8). They suggest that the activation by citrate results from removal of aluminum from the ATP complex by chelation with citrate. In this report we will show that those trivalent metals which form stable complexes with ATP at neutral pH are very tight inhibitors of yeast hexokinase, and that at pH 7 most of them