Burg M B, Peters E M
Laboratory of Kidney and Electrolyte Metabolism, National Heart, Lung, and Blood Institute, Bethesda, Maryland 20892, USA.
Am J Physiol. 1998 Apr;274(4):F762-5. doi: 10.1152/ajprenal.1998.274.4.F762.
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.
肾髓质中的尿素浓度足够高，足以干扰大分子，但细胞仍能存活并发挥功能。抗渗透压溶质假说认为，肾髓质中的甲胺类物质，如甘氨酸甜菜碱（甜菜碱）和甘油磷酸胆碱（GPC），可稳定大分子并对抗尿素的作用。尽管甜菜碱在体外可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侵害，但在体内和组织培养中，肾细胞对高浓度尿素的反应是积累GPC而非甜菜碱。一种提出的解释是，GPC比甜菜碱更有效地抵消尿素的作用。然而，我们之前发现，在抵消尿素对丙酮酸激酶活性的抑制作用方面，GPC的效果略逊于甜菜碱。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对核糖核酸酶A热稳定性降低的作用。我们发现尿素会降低热转变温度，而甜菜碱和GPC会提高热转变温度，二者对尿素的抵消作用大致相同。因此，在高浓度尿素环境下对GPC的偏好可能有其他原因，比如积累GPC的代谢成本较低。
