Effects of glycine betaine and glycerophosphocholine on thermal stability of ribonuclease

Effects of glycine betaine and glycerophosphocholine on thermal stability of ribonuclease
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DOI:
10.1152/ajprenal.1998.274.4.f762
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发表时间:
1998-04-01
影响因子:
4.2
通讯作者:
Peters, EM
Peters, EM
中科院分区:
医学2区
文献类型:
--
作者:
Burg, MB;Peters, EM

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肾髓质中的尿素含量高到足以干扰大分子,但细胞仍能存活并发挥功能。反渗透假说认为,甲胺,如甘氨酸甜菜碱(甜菜碱)和甘油磷酸胆碱(GPC)在肾髓质,稳定大分子和反对尿素的影响。虽然甜菜碱在体外抵消尿素对大分子的影响,并在组织培养中保护肾细胞免受尿素的影响,但在体内和组织培养中,肾细胞对高尿素的反应是积累GPC而不是甜菜碱。提出的解释是GPC比甜菜碱更有效地抵消尿素。然而,我们先前发现GPC在抵消尿素对丙酮酸激酶活性的抑制方面比甜菜碱的效果略差。为了测试另一种大分子,我们现在比较GPC和甜菜碱在抵消尿素降低RNA酶A的热稳定性方面的作用。我们发现,尿素降低热转变温度,甜菜碱和GPC增加它,抵消尿素大致相等。因此,对GPC响应高尿素的偏好可能有一些其他的基础,例如GPC积累的代谢成本较低。
Urea in renal medullas is sufficiently high to perturb macromolecules, yet the cells survive and function. The counteracting osmolytes hypothesis holds that methylamines, such as glycine betaine (betaine) and glycerophosphocholine (GPC) in renal medullas, stabilize macromolecules and oppose the effects of urea. Although betaine counteracts effects of urea on macromolecules in vitro and protects renal cells from urea in tissue culture, renal cells accumulate GPC rather than betaine in response to high urea both in vivo and in tissue culture. A proposed explanation is that GPC counteracts urea more effectively than betaine. However, we previously found GPC slightly less effective than betaine in counteracting inhibition of pyruvate kinase activity by urea. To test another macromolecule, we now compare GPC and betaine in counteracting reduction of the thermal stability of RNase A by urea. We find that urea decreases the thermal transition temperature and that betaine and GPC increase it, counteracting urea approximately equally. Therefore, the preference for GPC in response to high urea presumably has some other basis, such as a lower metabolic cost of GPC accumulation.