Triacsins A, B, C, and D are newly discovered compounds isolated from the culture filtrate of streptomyces which are known to inhibit nonspecific long chain acyl-CoA synthetase (EC 6.2.1.3.). These inhibitors have not been previously studied with regard to their effects on arachidonoyl-CoA synthetase, an enzyme which specifically utilizes arachidonate and other icosanoid precursor fatty acids. To explore this question, we used triacsin C, a potent inhibitor of the nonspecific acyl-CoA synthetase. Triacsin C was found to inhibit the action of arachidonoyl-CoA synthetase and the nonspecific enzyme in sonicates of HSDM1C1 mouse fibrosarcoma cells. Importantly, however, the triacsin concentration and length of pre-incubation with the enzymes could be adjusted to almost completely inhibit (greater than 80%) the nonspecific long chain acyl CoA-synthetase, with less than 20% inhibition of arachidonoyl-CoA synthetase. Using intact cultured cells exposed to 1 ug/ml triacsin for up to 15 minutes, we unexpectedly observed preferential inhibition of arachidonoyl-CoA synthetase activity. In intact cell studies, arachidonoyl-CoA synthetase was inhibited greater than 90%, with 55-60% inhibition of the nonspecific acyl-CoA synthetase. As additional evidence of its inhibition of acyl-CoA synthetase enzymes in intact cells, triacsin C inhibited both fatty acid uptake into cells and icosanoid production, metabolic processes which in certain cell types appear to be dependent on acyl-CoA synthetase activity. Thus, triacsin C is a novel inhibitor which can alter the fatty metabolism of intact cells. This compound can be of significant value in determining the specific cellular functions of the two acyl-CoA synthetase enzymes.

中文翻译：

---

Triacsin C：花生四烯酰辅酶A合成酶和非特异性长链酰基辅酶A合成酶的差异抑制剂。

Triacsins A，B，C和D是新发现的从链霉菌培养滤液中分离的化合物，已知这些化合物可抑制非特异性长链酰基CoA合成酶（EC 6.2.1.3。）。以前尚未就这些抑制剂对花生四烯酰辅酶A合成酶的作用进行过研究，花生四烯酰辅酶A是一种专门利用花生四烯酸酯和其他类花生酸前体脂肪酸的酶。为了探讨这个问题，我们使用了三酸甘油酯C，这是一种非特异性酰基辅酶A合成酶的有效抑制剂。发现Triacsin C在HSDM1C1小鼠纤维肉瘤细胞的超声处理中可抑制花生四烯酰辅酶A合成酶和非特异性酶的作用。但是重要的是 可以调节三端纤维蛋白的浓度和与酶预孵育的时间，以几乎完全抑制（大于80％）非特异性长链酰基辅酶A合成酶，而对花生四烯酰辅酶A合成酶的抑制作用不到20％。使用暴露于1 ug / ml甘油三酸达15分钟的完整培养细胞，我们出乎意料地观察到花生四烯酰辅酶A合成酶活性的优先抑制。在完整的细胞研究中，花生四烯酰辅酶A合成酶被抑制大于90％，非特异性酰基辅酶A合成酶被抑制55-60％。作为其在完整细胞中抑制酰基辅酶A合成酶的其他证据，三端酪蛋白C抑制了脂肪酸摄入细胞和类花生酸的产生，在某些细胞类型中，代谢过程似乎取决于酰基辅酶A合成酶的活性。从而，triacsin C是一种新型抑制剂，可以改变完整细胞的脂肪代谢。该化合物在确定两种酰基辅酶A合成酶的特定细胞功能方面可能具有重要价值。