ALBUMIN-LIPID INTERACTIONS - PROSTAGLANDIN STABILITY AS A PROBE FOR CHARACTERIZING BINDING-SITES ON VERTEBRATE ALBUMINS
ALBUMIN-LIPID INTERACTIONS - PROSTAGLANDIN STABILITY AS A PROBE FOR CHARACTERIZING BINDING-SITES ON VERTEBRATE ALBUMINS
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DOI：
10.1021/bi00524a033
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发表时间：
1981-01-01
期刊：
影响因子：
2.9
通讯作者：
WYNALDA, MA
中科院分区：
文献类型：
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作者：
FITZPATRICK, FA;WYNALDA, MA
确定了脊椎动物白蛋白对几种生理相关前列腺素[PG]稳定性的影响。所有天然存在的PG具有β-羟基酮基通过一级动力学分解，取决于在0.1M，pH7.4，37 ℃缓冲液中的白蛋白浓度。C.甚至亚生理水平的白蛋白（1-20 mg/ml）也显著降低了这些化合物的体外稳定性。带β的PG-羟基酮对白蛋白的反应顺序为它们的内在稳定性;即，不太稳定的化合物更敏感。白蛋白（20 mg/ml）：PG（100 μ g/ml）的摩尔比为1：1时，白蛋白的破坏作用几乎最大。白蛋白对PG没有破坏作用，而没有β-羟基酮。来自不同脊椎动物的白蛋白破坏的严重程度不同，但都是有效的。接近中性，在没有白蛋白的情况下，E型PG的分解实际上在脱水阶段暂停。在白蛋白存在下，脱水伴随着快速异构化反应（例如，PGA 1 →白蛋白显然将PG隔离到1个主要结合位点，并将它们暴露于其相关的高碱性微环境。这导致对PG稳定性的均匀和可预测的影响。所提出的模型系统成功地调和了关于白蛋白对PG稳定性的影响的明显异常或矛盾的报告。
The effect of vertebrate albumins on the stability of several physiologically relevant prostaglandins [PG] was determined. All naturally occurring PG with a .beta.-hydroxy ketone group decomposed by 1st-order kinetics, dependent on the albumin concentration in 0.1 M, pH 7.4, buffer at 37.degree. C. Even subphysiological levels of albumin (1-20 mg/ml) significantly reduced the stability of these compounds in vitro. The PG with a .beta.-hydroxy ketone responded to albumin in the order of their intrinsic stability; namely, less stable compounds were more susceptible. The destructive effect of albumin was nearly maximal at a 1:1 mole ratio of albumin (20 mg/ml):PG (100 .mu.g/ml). Albumin had no destructive effect on PG without a .beta.-hydroxy ketone. Albumins from different vertebrates varied in destructive severity, but all were effective. Near neutrality, in the absence of albumin, decomposition of E-type PG was practically suspended at the dehydration stage. In the presence of albumin, dehydration was accompanied by rapid isomerization reactions (e.g., PGA1 .fwdarw. PGB1) that occur only at an elevated pH. Albumin apparently sequesters PG to 1 principal binding site and exposes them to its associated highly alkaline microenvironment. This results in a uniform and predictable influence on PG stability. The proposed model system successfully reconciles apparently anomalous or contradictory reports regarding the effect of albumin on PG stability.