Roe D S, Vianey-Saban C, Sharma S, Zabot M T, Roe C R
The Kimberly S. Courtwright and Joseph W. Summers Institute of Metabolic Disease, Baylor University Medical Center, Dallas, TX 75226, USA.
Clin Chim Acta. 2001 Oct;312(1-2):55-67. doi: 10.1016/s0009-8981(01)00594-0.
The degradation of unsaturated fatty acids was examined in fibroblasts from 16 patients with very-long-chain acyl-CoA dehydrogenase (VLCAD) deficiency. Analysis of acylcarnitine intermediates following incubation of intact human cells with these compounds revealed that the milder clinical phenotypes could be distinguished from the severe cardiomyopathic phenotype. These findings may reflect more effective contributions of alternate pathways in the milder forms of the disease. Incubation of VLCAD-deficient cells with cis-9 or trans-9 unsaturated fatty acids indicate that VLCAD is largely responsible for the 2,3-dehydrogenation of cis-5 or trans-5 intermediates in fibroblasts. The first two cycles of beta-oxidation with oleic and linoleic acids occur in the absence of VLCAD activity suggesting the presence of an additional acyl-CoA dehydrogenase or alternate pathway for the oxidation of these unsaturated fatty acids. These observations have clinical relevance for determining diagnosis, prognosis and strategies for dietary treatment of these patients.
在16例极长链酰基辅酶A脱氢酶（VLCAD）缺乏症患者的成纤维细胞中研究了不饱和脂肪酸的降解情况。完整的人类细胞与这些化合物孵育后对酰基肉碱中间体进行分析发现，病情较轻的临床表型可与严重的心肌病表型区分开来。这些发现可能反映了在病情较轻的疾病形式中替代途径发挥了更有效的作用。用顺式-9或反式-9不饱和脂肪酸孵育VLCAD缺陷细胞表明，VLCAD在很大程度上负责成纤维细胞中顺式-5或反式-5中间体的2,3-脱氢反应。在缺乏VLCAD活性的情况下，油酸和亚油酸的前两个β-氧化循环仍会发生，这表明存在额外的酰基辅酶A脱氢酶或这些不饱和脂肪酸氧化的替代途径。这些观察结果对于确定这些患者的诊断、预后和饮食治疗策略具有临床意义。
