Regulation of adult and fetal myocardial phosphofructokinase. Relief of cooperativity and competition between fructose 2,6-bisphosphate, ATP, and citrate.
Regulation of adult and fetal myocardial phosphofructokinase. Relief of cooperativity and competition between fructose 2,6-bisphosphate, ATP, and citrate.
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DOI：
10.1016/s0021-9258(18)61634-5
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发表时间：
1987-02
期刊：
影响因子：
--
通讯作者：
J. Bristow;D. Bier;L. G. Lange
中科院分区：
文献类型：
--
作者：
J. Bristow;D. Bier;L. G. Lange
为了阐明果糖2,6-二磷酸在围产期心肌燃料从碳水化合物向脂肪酸转换中的生理作用，比较了果糖2,6-二磷酸对从胎儿和成年大鼠心脏纯化的磷酸果糖激酶的动力学影响。对于生理pH和ATP浓度下的两种酶，1微米果糖2,6-二磷酸诱导果糖6-磷酸的S0.5降低10倍以上，并完全消除亚基协同性。因此，果糖2,6-二磷酸可以降低果糖6-磷酸浓度变化对磷酸果糖激酶活性的影响。基于双倒数图和ATP抑制研究，成人心脏磷酸果糖激酶活性对ATP和柠檬酸盐浓度的生理变化比对果糖2,6-二磷酸浓度的变化更敏感。胎心磷酸果糖激酶对ATP浓度大于5 mM不太敏感，对柠檬酸盐抑制同样敏感。胎儿酶对果糖2,6-二磷酸的亲和力降低了15倍，使其对果糖2,6-二磷酸浓度的变化比成人心脏磷酸果糖激酶更敏感。总之，这些因素允许更大的磷酸果糖激酶活性在胎儿心脏，同时保持敏感的代谢控制。在胎儿和成人心脏中，果糖2,6-二磷酸主要是允许的：它消除亚基协同性，在它的存在下，磷酸果糖激酶的活性对细胞的能量平衡（反映在ATP浓度上）和其他燃料的可用性（反映在胞质柠檬酸盐浓度上）都非常敏感。
To clarify the physiological role of fructose 2,6-bisphosphate in the perinatal switching of myocardial fuels from carbohydrate to fatty acids, the kinetic effects of fructose 2,6-bisphosphate on phosphofructokinase purified from fetal and adult rat hearts were compared. For both enzymes at physiological pH and ATP concentrations, 1 microM fructose 2,6-bisphosphate induced a greater than 10-fold reduction in S0.5 for fructose 6-phosphate and it completely eliminated subunit cooperativity. Fructose 2,6-bisphosphate may thereby reduce the influence of changes in fructose 6-phosphate concentration on phosphofructokinase activity. Based on double-reciprocal plots and ATP inhibition studies, adult heart phosphofructokinase activity is more sensitive to physiological changes in ATP and citrate concentrations than to changes in fructose 2,6-bisphosphate concentrations. Fetal heart phosphofructokinase is less sensitive to ATP concentration above 5 mM and equally sensitive to citrate inhibition. The fetal enzyme has up to a 15-fold lower affinity for fructose 2,6-bisphosphate, rendering it more sensitive to changes in fructose 2,6-bisphosphate concentration than adult heart phosphofructokinase. Together, these factors allow greater phosphofructokinase activity in fetal heart while retaining sensitive metabolic control. In both fetal and adult heart, fructose 2,6-bisphosphate is primarily permissive: it abolishes subunit cooperativity and in its presence phosphofructokinase activity is extraordinarily sensitive to both the energy balance of the cell as reflected in ATP concentration and the availability of other fuels as reflected in cytosolic citrate concentration.