Mechanism of aluminum-induced inhibition of hepatic glycolysis: inactivation of phosphofructokinase.
Mechanism of aluminum-induced inhibition of hepatic glycolysis: inactivation of phosphofructokinase.
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发表时间：
1990-07
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通讯作者：
Zhi-Xin Xu;L. Fox;S. Melethil;L. Winberg;M. Badr
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作者：
Zhi-Xin Xu;L. Fox;S. Melethil;L. Winberg;M. Badr
铝是地壳中含量丰富的元素，与各种病理性疾病有关，最近发现低浓度的这种元素可抑制脑糖酵解。然而，尽管铝在肝脏中以高浓度积累，但尚未探索这种金属对肝脏中间代谢的潜在影响。在未处理大鼠的灌注肝脏中，乳酸和丙酮酸的最大产生速率（糖酵解）为93 +/-15 mumols/g/hr。（0.5毫克/千克，实验前6小时），最大速率仅为23 +/-4 mumols/g/hr。葡萄糖产生（糖原分解）和肝氧摄取没有被预先用铝处理显著改变。在禁食大鼠的肝脏中，用铝预处理并不影响果糖（5 mM）中的乳酸和丙酮酸的生成。这一发现表明，丙酮酸激酶不受铝的抑制，并暗示磷酸果糖激酶，己糖激酶和/或葡萄糖激酶作为铝对糖酵解的抑制作用的网站。在未经处理的大鼠肝匀浆中，铝浓度的增加对己糖激酶或葡萄糖激酶活性没有任何明显的影响，但确实导致磷酸果糖激酶活性的逐步降低。因此，铝诱导的抑制肝磷酸果糖激酶，在糖酵解途径中的一个重要的控制网站，是最有可能负责铝诱导的抑制肝糖酵解。
Aluminum, an abundant element in the earth's crust, has been implicated in various pathological disorders and low concentrations of this element have recently been shown to inhibit brain glycolysis. However, despite the fact that aluminum accumulates in high concentrations in the liver, potential effects of this metal on hepatic intermediary metabolism have not been explored. In perfused livers from untreated rats, maximal rates of production of lactate plus pyruvate (glycolysis) were 93 +/- 15 mumols/g/hr. Glycolysis was severely inhibited in livers from aluminum-treated rats (0.5 mg/kg, 6 hr before experiment) with maximal rates of only 23 +/- 4 mumols/g/hr. In contrast, glucose production (glycogenolysis) and hepatic oxygen uptake were not altered significantly by prior treatment with aluminum. In livers from fasted rats, pretreatment with aluminum did not influence gluconeogenesis or production of lactate and pyruvate from fructose (5 mM). This finding indicates that pyruvate kinase is not inhibited by aluminum and implicates phosphofructokinase, hexokinase and/or glucokinase as sites for the inhibitory effect of aluminum on glycolysis. In liver homogenates from untreated rats, increasing concentrations of aluminum did not show any appreciable effect on hexokinase or glucokinase activity but did cause progressive decreases in phosphofructokinase activity. Therefore, aluminum-induced inhibition of liver phosphofructokinase, an important control site in the glycolytic pathway, is most likely responsible for aluminum-induced inhibition of hepatic glycolysis.