Peroxisomal beta-oxidation enzyme proteins in adrenoleukodystrophy: distinction between X-linked adrenoleukodystrophy and neonatal adrenoleukodystrophy.
Peroxisomal beta-oxidation enzyme proteins in adrenoleukodystrophy: distinction between X-linked adrenoleukodystrophy and neonatal adrenoleukodystrophy.
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肾上腺脑白质营养不良中的过氧化物酶体β-氧化酶蛋白：X连锁肾上腺脑白质营养不良和新生儿肾上腺脑白质营养不良之间的区别。
DOI：
10.1073/pnas.84.5.1425
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发表时间：
1987
影响因子：
11.1
通讯作者：
Moser,HW
中科院分区：
文献类型：
--
作者：
Chen,WW;Watkins,PA;Osumi,T;Hashimoto,T;Moser,HW
X连锁肾上腺脑白质营养不良（ALD）、新生儿ALD和Zellweger脑肝肾综合征患者的血浆和组织中积累的极长链脂肪酸通过过氧化物酶体β氧化途径降解，该途径包括酰基-CoA氧化酶、双功能烯酰-CoA水合酶/3-羟酰基-CoA脱氢酶和β-酮硫解酶。据报道，齐薇格综合征患者的肝脏中存在所有三种酶蛋白的明显缺乏，齐薇格综合征是一种过氧化物酶体减少或缺失的疾病。过氧化物酶体在新生儿ALD中没有明显减少，在X连锁ALD中表现正常。过氧化物酶体β-氧化酶的免疫印迹分析显示，在新生儿ALD肝脏几乎完全缺乏双功能酶，类似于齐薇格组织中的发现。相反，酰基辅酶A氧化酶和β-酮硫解酶存在于新生儿ALD肝脏中，尽管硫解酶在新生儿ALD中似乎是前体形式（比成熟酶大2-3 kDa）。与新生儿ALD或Zellweger综合征不同，所有三种过氧化物酶体β-氧化酶都存在于X连锁ALD肝脏中。尽管没有在新生儿ALD肝脏的双功能酶蛋白，其mRNA的RNA印迹分析检测到这些患者的成纤维细胞。这些观察结果表明，缺乏双功能酶蛋白在新生儿ALD的结果从mRNA的异常翻译或降解的酶之前，其进入过氧化物酶体。
Very long chain fatty acids, which accumulate in plasma and tissues in X-linked adrenoleukodystrophy (ALD), neonatal ALD, and the Zellweger cerebrohepatorenal syndrome, are degraded by the peroxisomal beta-oxidation pathway, consisting of acyl-CoA oxidase, the bifunctional enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase, and beta-ketothiolase. A marked deficiency of all three enzyme proteins was reported in livers from patients with the Zellweger syndrome, a disorder in which peroxisomes are decreased or absent. Peroxisomes are not as markedly decreased in neonatal ALD and appear normal in X-linked ALD. Immunoblot analysis of the peroxisomal beta-oxidation enzymes revealed an almost complete lack of the bifunctional enzyme in neonatal ALD liver, similar to the finding in Zellweger tissue. In contrast, acyl-CoA oxidase and beta-ketothiolase were present in neonatal ALD liver, although the thiolase appeared to be in precursor form (2-3 kDa larger than the mature enzyme) in neonatal ALD. Unlike either neonatal ALD or Zellweger syndrome, all three peroxisomal beta-oxidation enzymes were present in X-linked ALD liver. Despite the absence in neonatal ALD liver of bifunctional enzyme protein, its mRNA was detected by RNA blot analysis in fibroblasts from these patients. These observations suggest that lack of bifunctional enzyme protein in neonatal ALD results from either abnormal translation of the mRNA or degradation of the enzyme prior to its entry into peroxisomes.