PEROXISOMAL BIFUNCTIONAL ENZYME DEFICIENCY
PEROXISOMAL BIFUNCTIONAL ENZYME DEFICIENCY
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DOI：
10.1172/jci113956
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发表时间：
1989-03-01
影响因子：
15.9
通讯作者：
MOSER, HW
中科院分区：
文献类型：
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作者：
WATKINS, PA;CHEN, WW;MOSER, HW
以新生儿肾上腺脑白质营养不良为临床特征的男婴评价过氧化物酶体功能。血浆和成纤维细胞中长链脂肪酸水平升高，培养成纤维细胞中长链脂肪酸的β -氧化显著受损。虽然血浆中胆汁酸中间体三羟基前列腺酸的水平略有升高，但植酸和l -管果酸的水平正常，培养成纤维细胞的浆磷脂原合成也正常。后三个参数区分这一情况从典型的新生儿肾上腺脑白质营养不良。此外，电子显微镜和过氧化氢酶亚细胞分布研究显示，与新生儿肾上腺白质营养不良相比，患者组织中存在过氧化物酶体。对过氧化物酶体β -氧化酶的免疫印迹研究显示，死后肝脏样本中缺乏双功能酶（烯酰辅酶a水合酶/3-羟基酰基辅酶a脱氢酶），而酰基辅酶a氧化酶和成熟形式的β -酮硫酶则存在。密度梯度离心的成纤维细胞匀浆证实完整的过氧化物酶体存在。免疫印迹显示成纤维细胞过氧化物酶体部分含有酰基辅酶a氧化酶和β -酮硫酶，但未检测到双功能酶。然而，Northern分析显示，编码双功能酶的mRNA存在于患者的成纤维细胞中。这些结果表明，该患者的主要生化缺陷是过氧化物酶双功能酶的缺乏。值得注意的是，该患者的表型类似于新生儿肾上腺脑白质营养不良症，仅通过临床研究无法将其与这种疾病区分开来。
Peroxisomal function was evaluated in a male infant with clinical features of neonatal adrenoleukodystrophy. Very long chain fatty acid levels were elevated in both plasma and fibroblasts, and beta-oxidation of very long chain fatty acids in cultured fibroblasts was significantly impaired. Although the level of the bile acid intermediate trihydroxycoprostanoic acid was slightly elevated in plasma, phytanic acid and L-pipecolic acid levels were normal, as was plasmalogen synthesis in cultured fibroblasts. The latter three parameters distinguish this case from classical neonatal adrenoleukodystrophy. In addition, electron microscopy and catalase subcellular distribution studies revealed that, in contrast to neonatal adrenoleukodystrophy, peroxisomes were present in the patient''s tissues. Immunoblot studies of peroxisomal beta-oxidation enzymes revealed that the bifunctional enzyme (enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase) was deficient in postmortem liver samples, whereas acyl-CoA oxidase and the mature form of beta-ketothiolase were present. Density gradient centrifugation of fibroblast homogenates confirmed that intact peroxisomes were present. Immunoblots of fibroblast peroxisomal fractions showed that they contained acyl-CoA oxidase and beta-ketothiolase, but bifunctional enzyme was not detected. Northern analysis, however, revealed that mRNA coding for the bifunctional enzyme was present in the patient''s fibroblasts. These results indicate that the primary biochemical defect in this patient is a deficiency of peroxisomal bifunctional enzyme. It is of interest that the phenotype of this patient resembled neonatal adrenoleukodystrophy and would not have been distinguished from this disorder by clinical study alone.