Buffington C K, Kitabchi A E
Biochem Biophys Res Commun. 1984 Aug 30;123(1):202-9. doi: 10.1016/0006-291x(84)90399-1.
The effects of the second generation sulfonylurea, glyburide, on the pyruvate dehydrogenase multienzyme complex (PDC) of rat myocardial tissue were examined using rat ventricular slices and isolated mitochondria. Therapeutic concentrations (10(-7) to 10(-6)M) of glyburide produced a 30% increase in the decarboxylation of [1(-14)C] pyruvate by the PDC of ventricular tissue. Addition of glyburide to intact rat heart mitochondria stimulated activity of the PDC in a time- and concentration-dependent manner. Half-maximal stimulation of the enzyme occurred with 6 X 10(-5)M glyburide and maximal activation of the enzyme was achieved with 1 X 10(-4)M glyburide. At the height of stimulation, PDC activities were 6-fold greater than those observed under control conditions with succinate alone. When mitochondria were disrupted by sonication or freeze-thawing, glyburide produced no stimulation of pyruvate decarboxylation. We conclude that glyburide directly stimulates the decarboxylation of pyruvate by the PDC of the myocardium. Furthermore, the presence of intact mitochondria is necessary for the stimulatory action of glyburide on the PDC.
使用大鼠心室切片和分离的线粒体，研究了第二代磺酰脲类药物格列本脲对大鼠心肌组织丙酮酸脱氢酶多酶复合物（PDC）的影响。治疗浓度（10^(-7)至10^(-6)M）的格列本脲使心室组织的PDC对[1-^(14)C]丙酮酸的脱羧作用增加了30%。向完整的大鼠心脏线粒体中添加格列本脲以时间和浓度依赖性方式刺激了PDC的活性。6×10^(-5)M的格列本脲可使该酶达到半数最大刺激，1×10^(-4)M的格列本脲可使该酶达到最大激活。在刺激高峰时，PDC活性比仅用琥珀酸作为对照条件下观察到的活性高6倍。当线粒体通过超声处理或冻融破坏时，格列本脲对丙酮酸脱羧没有刺激作用。我们得出结论，格列本脲直接刺激心肌的PDC对丙酮酸的脱羧作用。此外，完整线粒体的存在是格列本脲对PDC产生刺激作用所必需的。
