Telles-Pupulin A R, Salgueiro-Pagadigorria C L, Bracht A, Ishii-Iwamoto E L
Department of Clinical Sciences, University of Maringá, Brazil.
Comp Biochem Physiol C Pharmacol Toxicol Endocrinol. 1998 Jul;120(1):43-51. doi: 10.1016/s0742-8413(98)00004-8.
The effects of fusaric acid on hepatic energy metabolism were measured. Three experimental systems were employed: (a) Intact rat liver mitochondria; (b) freeze-thawing disrupted mitochondria; and (c) the isolated perfused rat liver. Fusaric acid affects mitochondrial energy metabolism by at least three modes of action: (1) Inhibition of succinate-dehydrogenase (in the 10(-3)-10(-2) M range); (2) inhibition of oxidative phosphorylation (in the 10(-5)-10(-4) M range); and (3) inhibition of alpha-ketoglutarate-dehydrogenase (in the 10(-5)-10(-4) M range). The inhibition of oxidative phosphorylation seems to be the result of a direct action on the ATP-synthase/ATPase without significant inhibition of the ATP/ADP exchange. In the isolated perfused rat liver, fusaric acid inhibits oxygen uptake and gluconeogenesis from pyruvate, the latter being strictly dependent on intramitochondrially generated ATP. The effects of fusaric acid on rat liver mitochondria are similar to those reported previously for maize root mitochondria. However, except for the action on succinate-dehydrogenase, rat liver mitochondria are approximately two orders of magnitude more sensitive than maize root mitochondria.
测定了镰刀菌酸对肝脏能量代谢的影响。采用了三个实验系统：(a) 完整的大鼠肝脏线粒体；(b) 冻融破碎的线粒体；以及 (c) 离体灌注的大鼠肝脏。镰刀菌酸通过至少三种作用方式影响线粒体能量代谢：(1) 抑制琥珀酸脱氢酶（在10⁻³ - 10⁻² M范围内）；(2) 抑制氧化磷酸化（在10⁻⁵ - 10⁻⁴ M范围内）；以及 (3) 抑制α-酮戊二酸脱氢酶（在10⁻⁵ - 10⁻⁴ M范围内）。氧化磷酸化的抑制似乎是对ATP合酶/ATP酶直接作用的结果，而对ATP/ADP交换没有明显抑制。在离体灌注的大鼠肝脏中，镰刀菌酸抑制氧气摄取和丙酮酸的糖异生，后者严格依赖线粒体内产生的ATP。镰刀菌酸对大鼠肝脏线粒体的影响与先前报道的玉米根线粒体的影响相似。然而，除了对琥珀酸脱氢酶的作用外，大鼠肝脏线粒体的敏感性比玉米根线粒体高约两个数量级。
