Molecular analysis of peroxisomal beta-oxidation enzymes in infants with Zellweger syndrome and Zellweger-like syndrome: further heterogeneity of the peroxisomal disorder.
Molecular analysis of peroxisomal beta-oxidation enzymes in infants with Zellweger syndrome and Zellweger-like syndrome: further heterogeneity of the peroxisomal disorder.
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齐薇格综合征和齐薇格样综合征婴儿过氧化物酶体 β-氧化酶的分子分析：过氧化物酶体疾病的进一步异质性。
DOI：
10.1016/0009-8981(88)90121-0
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发表时间：
1988
期刊：
影响因子：
--
通讯作者：
T. Hashimoto
中科院分区：
文献类型：
--
作者：
Yasuyuki Suzuki;N. Shimozawa;T. Orii;N. Igarashi;N. Kono;T. Hashimoto
对过氧化物酶体β-氧化酶的生物合成进行了研究，试图阐明 3 名齐薇格综合征婴儿和 1 名齐薇格样综合征婴儿中这些酶的蛋白质缺乏的机制，其临床和生化结果与齐薇格综合征一致，但过氧化物酶体是通过电子显微镜检测到的。在两种综合征中几乎检测不到过氧化物酶体β-氧化酶蛋白、酰基辅酶A氧化酶、双功能蛋白和3-酮脂酰辅酶A硫解酶。从患有每种综合征的一名患者和三名对照者的肝脏中提取的总肝RNA在存在[35S]蛋氨酸的情况下在兔网织红细胞裂解物蛋白质合成系统中进行翻译。在两名患者中检测到的所有过氧化物酶体 β-氧化酶的可翻译 mRNA 水平与对照组基本相同。对对照成纤维细胞的脉冲标记和追踪实验表明，首先合成了酰基辅酶A氧化酶的72 kDa亚基，然后从72 kDa亚基加工出52 kDa和21 kDa亚基。在 Zellweger 综合征患者中，酰基辅酶 A 氧化酶的 52 kDa 和 21 kDa 亚基很少合成。在该患者中，过氧化物酶体 3-酮酰基-CoA 硫解酶的成熟形式也不是从其前体形式加工而来。我们认为齐薇格样综合征是过氧化物酶体疾病的一种新变异形式，其中过氧化物酶体的生物发生是完整的，而相反，在齐薇格综合征患者中，过氧化物酶体的生物发生被认为是有缺陷的。齐薇格样综合征中β-氧化酶的多种缺陷被认为是由这些酶的运输或定位缺陷引起的。我们的分子分析表明，齐薇格和齐薇格样综合征患者体内合成了过氧化物酶体 β-氧化酶，但这些酶不能正常加工并迅速降解。
The biosynthesis of enzymes of peroxisomal β-oxidation was investigated in an attempt to elucidate the mechanism of deficiencies of proteins of these enzymes in 3 infants with Zellweger syndrome and in a baby with Zellweger-like syndrome with clinical and biochemical findings consistent with Zellweger syndrome except that the peroxisomes were detected electronmicroscopically. Enzyme proteins of peroxisomal β-oxidation, acyl-CoA oxidase, bifunctional protein and 3-ketoacyl-CoA thiolase were hardly detectable, in both syndromes. Total hepatic RNA extracted from the liver of one patient with each syndrome and three controls was translated in a rabbit reticulocyte lysate protein-synthesizing system in the presence of [35S]methionine. Translatable mRNAs for all of the peroxisomal β-oxidation enzymes were detected in both patients at much the same levels seen in the controls. Pulse labelling and chase experiments of fibroblasts from the control revealed that the 72 kDa subunit of acyl-CoA oxidase was first synthesized, after which the 52 kDa and 21 kDa subunits were processed from the 72 kDa subunit. In the patient with Zellweger syndrome, little of the 52 kDa and 21 kDa subunits of acyl-CoA oxidase were synthesized. The mature form of peroxisomal 3-ketoacyl-CoA thiolase was also not processed from its precursor form, in this patient.We consider that Zellweger-like syndrome is a new variant form of a peroxisomal disorder in which biogenesis of peroxisomes is intact, while in contrast, the biogenesis of peroxisome is considered to be defective in those with Zellweger syndrome. Multiple defects of enzymes of β-oxidation in Zellweger-like syndrome are assumed to be caused by a defect of transport or localization of these enzymes. Our molecular analyses indicate that the enzymes of peroxisomal β-oxidation are synthesized in patients with Zellweger and Zellweger-like syndrome but that these enzymes are not processed normally and are degraded rapidly.
影响因子：
5.1
作者：
GOLDFISCHER, S;COLLINS, J;VANHOOF, F
通讯作者：
VANHOOF, F
脑肝肾（Zellweger）综合征和新生儿肾上腺脑白质营养不良：表型和超长链脂肪酸积累的相似性。
DOI：
--
发表时间：
1982
期刊：
The Johns Hopkins medical journal
影响因子：
--
作者：
Brown3rd,FR;McAdams,AJ;Cummins,JW;Konkol,R;Singh,I;Moser,AB;Moser,HW
通讯作者：
Moser,HW