Proton-dependent inhibition of yeast and brain hexokinases by aluminum in ATP preparations.
Proton-dependent inhibition of yeast and brain hexokinases by aluminum in ATP preparations.
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ATP 制剂中铝对酵母和脑己糖激酶的质子依赖性抑制。
DOI：
10.1073/pnas.76.10.5080
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发表时间：
1979
影响因子：
11.1
通讯作者：
S. Colowick
中科院分区：
文献类型：
--
作者：
F. Womack;S. Colowick
在ATP制剂中作为污染物存在的铝在pH 7.0或更低时可引起酵母己糖激酶P-II活性的强烈抑制，但在pH 7.5或更高时几乎没有或没有抑制作用。柠檬酸盐，3-磷酸甘油酸，苹果酸，磷酸盐，和儿茶酚胺，所有这些都已被描述为在低pH值的己糖激酶的激活剂逆转的抑制。我们建议，这些代理商激活酶仅凭借他们的能力，以协调与铝存在于测定系统中。铝的存在也是在低pH下观察到的相对于Mg的“负协同性”的原因。ATP浓度，也就是说在低Mg时，铝的缓蚀作用是无竞争性的。ATP浓度，但在高镁变得有竞争力。ATP浓度。抑制作用被认为是由于Al的络合物的形成。ATP与酶的解离常数（Ki）为0.1 μ M。酵母己糖激酶P-I对A1的敏感性略低于己糖激酶P-II，酵母葡萄糖激酶未受到可检测的影响。大鼠大脑中的己糖激酶（I型）显示出铝对pH依赖性的抑制作用，类似于酵母己糖激酶中观察到的抑制作用，而大鼠肌肉（II型）酶的敏感性较低，这表明可能与人类铝脑病有关。
The aluminum present as a contaminant in ATP preparations can cause strong inhibition of yeast hexokinase P-II activity at pH 7.0 or below but has little or no inhibitory effect at a pH of 7.5 or greater. The inhibition is reversed by citrate, 3-phosphoglycerate, malate, phosphate, and catecholamines, all of which have previously been described as activators of hexokinase at low pH. We suggest that these agents activate the enzyme only by virtue of their ability to coordinate with aluminum present in the assay system. The presence of aluminum is also responsible for the "negative cooperativity" observed at low pH with respect to Mg . ATP concentration--i.e., the inhibition by aluminum is uncompetitive at low Mg . ATP concentrations but becomes competitive at high Mg . ATP concentrations. The inhibition is thought to be due to formation of a complex of Al . ATP with the enzyme, with a dissociation constant (Ki) of 0.1 microM. Yeast hexokinase P-I is somewhat less sensitive to A1 than is hexokinase P-II, and yeast glucokinase is not detectably affected. The hexokinase in rat brain (type I) shows a pH-dependent inhibition by Al similar to that observed with the yeast hexokinases, whereas the rat muscle (type II) enzyme is less sensitive, suggesting a possible relationship to aluminum encephalopathy in man.