Christensen E, Brandt N J
Clin Chim Acta. 1978 Sep 1;88(2):267-76. doi: 10.1016/0009-8981(78)90431-x.
Three patients with glutaric aciduria have been shown to possess a partial but severe defect of the enzyme glutaryl-CoA dehydrogenase in isolated leucocytes and cultured skin fibroblasts. They could readily be distinguished from heterozygotes by measuring the activity of this enzyme, as shown in a study of the two families involved. The activity of glutaryl-CoA dehydrogenase in normal cultured amniotic fluid cells was comparable to the activity in normal cultured skin fibroblasts indicating the possibility of prenatal diagnosis. Without flavin adenine dinucleotide added to the assay mixture, the activity of glutaryl-CoA dehydrogenase in fibroblasts from normal individuals was very much reduced and similar to the activity in the patients, but after addition of flavin adenine dinucleotide to saturation the activity increased 20-fold in normal subjects while only a very slight increase could be demonstrated in the patients. The Michaelis constant for the substrate glutaryl-CoA was similar for both normal and patient cell lines. The optimum assay conditions for the enzyme in cultured fibroblasts from normal individuals have been established. In contrast to our patients, we found no activity in a fibroblast cell line from a patient with glutaric aciduria diagnosed elsewhere.
已证实三名戊二酸尿症患者在分离的白细胞和培养的皮肤成纤维细胞中存在部分但严重的戊二酰辅酶A脱氢酶缺陷。通过测量该酶的活性，他们很容易与杂合子区分开来，这在对所涉及的两个家族的研究中得到了证实。正常培养的羊水细胞中戊二酰辅酶A脱氢酶的活性与正常培养的皮肤成纤维细胞中的活性相当，这表明产前诊断具有可能性。在测定混合物中不添加黄素腺嘌呤二核苷酸时，正常个体成纤维细胞中戊二酰辅酶A脱氢酶 的活性大大降低，与患者的活性相似，但在添加黄素腺嘌呤二核苷酸至饱和后，正常受试者的活性增加了20倍，而患者仅表现出非常轻微的增加。正常和患者细胞系中底物戊二酰辅酶A的米氏常数相似。已确定了正常个体培养的成纤维细胞中该酶的最佳测定条件。与我们的患者不同，我们在其他地方诊断出的一名戊二酸尿症患者的成纤维细胞系中未发现活性。
