水杨酰胺在离体大鼠肝细胞中的硫酸结合反应和葡萄糖醛酸化反应。

Sulfoconjugation and glucuronidation of salicylamide in isolated rat hepatocytes.

作者信息

Koike M, Sugeno K, Hirata M

出版信息

J Pharm Sci. 1981 Mar;70(3):308-11. doi: 10.1002/jps.2600700322.

Abstract

Sulfoconjugation and glucuronidation of salicylamide by isolated hepatocytes were examined with various concentrations of salicylamide and sodium sulfate. The ratio of sulfate to glucuronide formed changed markedly, depending on the concentrations of salicylamide and inorganic sulfate in the medium. The apparent Km value of sulfoconjugation for salicylamide was 0.006 mM, while its Vmax value varied depending on the concentration of inorganic sulfate (e.g., 2.1 and 0.5 nmoles/min/10(6) cells at 1.2 and 0.5 mM inorganic sulfate, respectively). The Km and Vmax values of glucuronidation for salicylamide were 0.19 mM and 1.28 nmoles/min/10(6) cells, respectively, in the absence of sodium sulfate. Glucuronidation was suppressed in the presence of inorganic sulfate. The suppression could be attributable to the competitive consumption of salicylamide by sulfotransferase. Additional in vivo experiments revealed that an extra amount of salicylamide markedly lowered the blood inorganic sulfate levels of rats. The significance of the finding is discussed in conjunction with the variation of the Vmax value of sulfoconjugation with the inorganic sulfate concentration.

摘要

用不同浓度的水杨酰胺和硫酸钠检测了分离的肝细胞对水杨酰胺的硫酸结合和葡萄糖醛酸化作用。形成的硫酸盐与葡萄糖醛酸苷的比例显著变化，这取决于培养基中水杨酰胺和无机硫酸盐的浓度。水杨酰胺硫酸结合的表观 Km 值为 0.006 mM，而其 Vmax 值则根据无机硫酸盐的浓度而变化（例如，在 1.2 和 0.5 mM 无机硫酸盐时，分别为 2.1 和 0.5 纳摩尔/分钟/10⁶ 个细胞）。在没有硫酸钠的情况下，水杨酰胺葡萄糖醛酸化的 Km 和 Vmax 值分别为 0.19 mM 和 1.28 纳摩尔/分钟/10⁶ 个细胞。在无机硫酸盐存在的情况下，葡萄糖醛酸化受到抑制。这种抑制可能归因于磺基转移酶对水杨酰胺的竞争性消耗。额外的体内实验表明，额外剂量的水杨酰胺显著降低了大鼠的血液无机硫酸盐水平。结合硫酸结合的 Vmax 值随无机硫酸盐浓度的变化对这一发现的意义进行了讨论。