Abnormal fatty acid composition of biotin-responsive multiple carboxylase deficiency fibroblasts.
Abnormal fatty acid composition of biotin-responsive multiple carboxylase deficiency fibroblasts.
复制标题
生物素响应性多重羧化酶缺乏成纤维细胞的脂肪酸组成异常。
DOI：
10.1007/bf01805530
复制
发表时间：
1989
影响因子：
4.2
通讯作者：
Fleming,SE
中科院分区：
文献类型：
--
作者：
Packman,S;Whitney,SC;Fitch,M;Fleming,SE
生物素反应性多种羧化酶缺乏症的临床和生化相关性表明，脂肪生成障碍在疾病的发病机制中起作用。特别是，生物素依赖性乙酰辅酶A羧化酶的活性和脂肪酸的去合成在突变成纤维细胞中降低。在目前的工作中，我们研究了这些缺陷的生化后果，并记录和描述了一个异常的脂肪酸组成的全羧化酶合成酶缺陷成纤维细胞。在生物素限制性培养基中生长后，突变细胞的总脂肪酸含量降低。16：0、18：0和20：3N9脂肪酸的百分比显著降低，长链脂肪酸的比例增加或维持在对照水平。在缺乏生物素的突变细胞中，16：0、16：1、18：0、18：1和20：3 N9脂肪酸的细胞含量减少，而长链脂肪酸的含量保持在对照水平。我们推测，改变的脂肪酸池的成分可能不成比例地纳入突变细胞中的复杂脂质，对多种羧化酶缺乏症表型的病理影响。
Clinical and biochemical correlations in the biotin‐responsive multiple carboxylase deficiencies have suggested that disordered lipogenesis plays a role in the pathogenesis of the disease. In particular, the activity of biotin‐dependent acetyl CoA carboxylase and thede novosynthesis of fatty acids are reduced in mutant fibroblasts. In the present work, we examine the biochemical consequences of these deficiencies, and document and characterize an abnormal fatty acid composition in holocarboxylase synthetase deficiency fibroblasts. Following growth in biotin‐restricted medium, the total fatty acid content of mutant cells is reduced. There were significant reductions in the percentage as 16:0, 18:0 and 20:3N9 fatty acids, with the proportion of longer‐chain fatty acids either increased or maintained at control levels. The cellular content of 16:0, 16:1, 18:0, 18:1 and 20:3N9 fatty acids was reduced, while that of the longer‐chain fatty acids was preserved at control levels in mutant cells deprived of biotin. We speculate that the components of the altered fatty acid pools may be disproportionately incorporated into complex lipids in mutant cells, with pathologic effects on the multiple carboxylase deficiency phenotype.