Department of Neurology, Martin Luther University Halle-Wittenberg, Ernst-Grube-Strasse 40, 06120, Halle (Saale), Germany.
J Bioenerg Biomembr. 2018 Dec;50(6):461-466. doi: 10.1007/s10863-018-9781-9. Epub 2019 Jan 3.
The phospholipid environment of the mitochondrial inner membrane, which contains large amounts of cardiolipin, could play a key role in transport of the long chain fatty acids. In the present study, the pre-incubation of cardiolipin with the wild type carnitine palmitoyltransferase (CPT) II led to a more than 1.5-fold increase of enzyme activity at physiological temperatures. At higher temperatures, however, there was a pronounced loss of activity. The most frequent variant S113L showed even at 37 °C a great activity loss. Pre-incubation of the wild type with both malonyl-CoA and cardiolipin counteracted the positive effect of cardiolipin. Malonyl-CoA, however, showed no inhibition effect on the variant in presence of cardiolipin. The activity loss in presence of cardiolipin at fever simulating situations was more pronounced for the variant comparing to the wild type. The reason might be a disturbed membrane association or a blockage of the active center of the mutated enzyme.
线粒体膜的磷脂环境，其中含有大量的心磷脂，可能在长链脂肪酸的运输中起关键作用。在本研究中，心磷脂与野生型肉毒碱棕榈酰转移酶（CPT）II 的预孵育导致在生理温度下酶活性增加了 1.5 倍以上。然而，在较高温度下，活性明显丧失。最常见的变体 S113L 甚至在 37°C 时表现出很大的活性丧失。野生型与丙二酰 CoA 和心磷脂的预孵育抵消了心磷脂的正效应。然而，在存在心磷脂的情况下，丙二酰 CoA 对变体没有抑制作用。在模拟发热情况下，变体在心磷脂存在下的活性丧失比野生型更为明显。原因可能是膜结合受到干扰或突变酶的活性中心受阻。
