Morton R E, Hartz J W, Reitz R C, Waite B M, Morris H P
Biochim Biophys Acta. 1979 May 25;573(2):321-31. doi: 10.1016/0005-2760(79)90065-1.
We have investigated the role of the microsomal oxidative desaturase in defining the aberrant phosphoglyceride fatty acid composition of hepatomas. The microsomal delta 9-stearoyl-CoA, delta 6-oleoyl(linolenoyl)-CoA, and delta 5-eicosatrienoyl-CA desaturase activities were studied in control and host liver and in the poorly differentiated Morris 7777 hepatoma. The delta 9-stearoyl-CoA desaturase of the hepatoma was significantly decreased (42%) relative to control liver, yet the hepatoma specific activity was twice that of host liver. Additionally, the specific activity of the delta 9-stearoyl-CoA desaturase of the tumor was found to decrease with increasing tumor weight. Also this desaturase was inactivated by freezing and thawing. The delta 6-oleoyl(linolenoyl)-CoA and delta 5-eicosatrienoyl-CoA desaturases of the hepatoma were 39% and 4% of control, respectively. The electron transport components involved in the desaturase system were reduced, although this did not appear to be rate-limiting. In addition, two competing metabolic reactions which could lower the observed desaturase activities, hydrolysis of the thioester and incorporation of substrate acyl-CoA molecules into glycerides, did not appear to be responsible for the lowered desaturase activities of the tumor. Thus, it appears that reduced levels of the desaturases themselves may be responsible for the observed activities. These results indicate that the capacity of the hepatoma to biosynthesize polyunsaturated fatty acids is greatly reduced and this is consistent with the decreased polyene content observed in many neoplasms.
我们研究了微粒体氧化去饱和酶在确定肝癌异常磷酸甘油酯脂肪酸组成中的作用。在对照肝脏、宿主肝脏以及低分化的莫里斯7777肝癌中，研究了微粒体Δ9-硬脂酰辅酶A、Δ6-油酰（亚麻酸）辅酶A和Δ5-二十碳三烯酰辅酶A去饱和酶的活性。肝癌的Δ9-硬脂酰辅酶A去饱和酶相对于对照肝脏显著降低（42%），但其比活性是宿主肝脏的两倍。此外，发现肿瘤的Δ9-硬脂酰辅酶A去饱和酶的比活性随肿瘤重量增加而降低。而且这种去饱和酶在冻融后失活。肝癌的Δ6-油酰（亚麻酸）辅酶A和Δ5-二十碳三烯酰辅酶A去饱和酶分别为对照的39%和4%。去饱和酶系统中涉及的电子传递成分减少，尽管这似乎不是限速因素。此外，两种可能降低观察到的去饱和酶活性的竞争性代谢反应，硫酯的水解以及底物酰基辅酶A分子掺入甘油酯中，似乎并不是肿瘤去饱和酶活性降低的原因。因此，似乎去饱和酶本身水平的降低可能是观察到的活性的原因。这些结果表明，肝癌生物合成多不饱和脂肪酸的能力大大降低，这与在许多肿瘤中观察到的多烯含量降低是一致的。
