Correlation between loss of alkaline phosphatase activity and accumulation of calcium during matrix vesicle-mediated mineralization.
Correlation between loss of alkaline phosphatase activity and accumulation of calcium during matrix vesicle-mediated mineralization.
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发表时间：
1988-12
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通讯作者：
B. Genge;G. R. Sauer;L. N. Wu;F. M. McLean;R. Wuthier
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作者：
B. Genge;G. R. Sauer;L. N. Wu;F. M. McLean;R. Wuthier
已知碱性磷酸酶（AP）的骨/肝/肾同工酶的活性对于发育中的骨的矿化至关重要，尽管其作用尚不清楚。现在报道的工作探讨了这种含Zn 2+的酶的活性变化，这种酶在基质囊泡（MV）的Ca 2+积累过程中发生。AP活性的显著损失（高达65-70%）被发现伴随着MV的Ca ~（2+）积累。这两个事件在时间和数量上都高度相关。调查可能的原因表明，在AP活性的下降在Ca 2+摄取过程中是不是由于蛋白酶的作用，而是由于与发展中的矿物相，金属离子（Zn 2+和Mg 2+）的损失从酶的活性位点的相互作用，并伴随着不可逆的变性的酶。蛋白酶抑制剂并没有保护AP在矿化过程中的活性损失，相反，蛋白酶治疗，这逐渐破坏MV积累Ca 2+的能力，实际上减少AP活性的损失。这些研究结果清楚地表明，AP是存在于MV矿化的网站，其催化活性大大降低了矿化过程。
Activity of the bone/liver/kidney isozyme of alkaline phosphatase (AP) is known to be critical for mineralization in developing bone, although its role is unclear. The work now reported explores changes in the activity of this Zn2+-containing enzyme that occur during Ca2+ accumulation by matrix vesicles (MV). A marked loss (up to 65-70%) in AP activity was found to accompany Ca2+ accumulation by MV. These two events were highly correlated, both temporally and quantitatively. Investigation into possible causes revealed that the decline in AP activity during Ca2+ uptake was not due to action of proteases but rather resulted from interaction with the developing mineral phase, loss of metal ions (Zn2+ and Mg2+) from the active site of the enzyme, and concomitant irreversible denaturation of the enzyme. Protease inhibitors did not protect AP from loss of activity during mineralization; in contrast, protease treatments, which progressively destroyed the ability of MV to accumulate Ca2+ actually reduced loss of AP activity. These findings clearly demonstrate that AP is present at the site of MV mineralization and that its catalytic activity is profoundly reduced by the mineralization process.