Rein K A, Borrebaek B, Bremer J
Biochim Biophys Acta. 1979 Sep 28;574(3):487-94. doi: 10.1016/0005-2760(79)90245-5.
A partial inhibition of acylcarnitine oxidation by arsenite in rat liver mitochondria has been studied. This inhibition is confined to the thiolase(s). The inhibition was observed also in the presence of malate, indicating no selective effect on ketogenesis. Ketogenesis from acetyl-CoA was inhibited by arsenite. Mitochondrial CoA was acylated by acylcarnitine nearly as rapidly in the presence of arsenite as in its absence. Thus, arsenite did not interfere with the availibility of CoA in the mitochondria. No effect of arsenite on enzymes of beta-oxidation other than the thiolase(s) was observed. When arsenite and acylcarnitine were added simultaneously to mitochondria, there was a delay before maximal inhibition of oxygen uptake occurred. When the mitochondria were preincubated with arsenite before addition of acylcarnitine, the inhibitory effect on oxygen utilization was initially large, but then partially repealed. Similar time delays were observed in the activity of acetoacetyl-CoA thiolase of disrupted mitochondria depending on the sequence of arsenite and acetoacetyl-CoA addition. It is suggested that substrate and arsenite complete for the reactive sulfhydryl group at the active site of the thiolase(s).
研究了亚砷酸盐对大鼠肝脏线粒体中酰基肉碱氧化的部分抑制作用。这种抑制作用仅限于硫解酶。在苹果酸存在的情况下也观察到了这种抑制作用，表明对生酮作用没有选择性影响。亚砷酸盐抑制了由乙酰辅酶A生成酮体的过程。在线粒体中，无论有无亚砷酸盐存在，酰基肉碱对线粒体辅酶A的酰化速度几乎一样快。因此，亚砷酸盐不会干扰线粒体中辅酶A的可用性。未观察到亚砷酸盐对除硫解酶之外的β-氧化酶有影响。当亚砷酸盐和酰基肉碱同时添加到线粒体中时，在氧摄取受到最大抑制之前会有延迟。当线粒体在添加酰基肉碱之前先用亚砷酸盐预孵育时，对氧利用的抑制作用最初很大，但随后部分解除。根据亚砷酸盐和乙酰乙酰辅酶A添加顺序的不同，在线粒体破裂后乙酰乙酰辅酶A硫解酶的活性中也观察到了类似的时间延迟。有人提出，底物和亚砷酸盐竞争硫解酶活性位点上的反应性巯基。
