Peroxisomal disorders: clinical commentary and future prospects.
Peroxisomal disorders: clinical commentary and future prospects.
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过氧化物酶体疾病：临床评论和未来前景。
DOI：
10.1002/ajmg.1320300311
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发表时间：
1988
期刊：
影响因子：
--
通讯作者：
Hajra,AK
中科院分区：
文献类型：
--
作者：
Wilson,GN;Holmes,RD;Hajra,AK
本文从临床角度综述了过氧酶体疾病的分类、生化和分子生物学方面的最新进展。Zellweger综合征、新生儿肾上腺脑白质营养不良、婴儿Refsum病、高管性酸血症、点状软骨发育不良和Leber黑素症等疾病具有共同的表型，涉及多种过氧化物酶缺乏。这些疾病与各种代谢异常有关，这些代谢异常在出生前或出生后的诊断中很有用，并将这些疾病与其他疾病区分开来，如X-连锁肾上腺脑白质营养不良、成人Refsum病、I型高草酸尿症和再生障碍症。由于最近的研究强调其发育的可变性和组织的异质性，过氧体的结构在历史上很难量化。通过饮食或药物手段操纵这种结构的能力提供了一种新的治疗方法。在分子水平上，负责脂肪酸β-氧化或乙醚脂肪合成的过氧体酶的缺乏反映了由于异常的过氧酶体而导致的蛋白质降解的增强；β-氧化酶的信使RNA在过氧素体疾病中正常转录，并可被过氧酶体增殖物增加。在Zellweger综合征中，至少有一种完整的过氧化体结构蛋白是正常合成的。基本缺陷的假设包括对进口蛋白质的调节、摄取或辅酶刺激缺陷，以及生物合成缺陷。这一缺陷的一个线索可能是过氧化物体和线粒体的相似进化史，这可以解释齐薇格综合征中它们共同的变化。
Recent progress in the classification, biochemistry, and molecular biology of peroxisomal disorders is reviewed from a clinical perspective. Diseases such as Zellweger syndrome, neonatal adrenoleukodystrophy, infantile Refsum disease, hyperpipecolic acidemia, chondrodysplasia punctata, and Leber amaurosis share a common phenotype and involve deficiency of multiple peroxisomal enzymes. These disorders are associated with diverse metabolic abnormalities which are useful in pre‐ or postnatal diagnosis and distinguish these disorders from others such as X‐linked adrenoleukodystrophy, adult Refsum disease, hyperoxaluria type I, and acatalasemia. Peroxisome structure is difficult to quantify historically, since recent studies emphasize its developmental variability and tissue heterogeneity. The ability to manipulate this structure by dietary or pharmaceutical means provides a novel approach to therapy. At the molecular level, deficiency of peroxisomal enzymes responsible for fatty acid beta‐oxidation or ether lipid synthesis reflects enhanced protein degradation due to abnormal peroxisomes; messenger RNA for the beta‐oxidation enzymes is transcribed normally in peroxisomal disorders and can be increased by peroxisome proliferators. At least one integral structural protein of the peroxisome is synthesized normally in Zellweger syndrome. Hypotheses for the basic defect include defective regulation, uptake, or coenzyme stimulation of imported proteins, as well as defective biosynthesis. One clue to this defect may be a similar evolutionary history of peroxisomes and mitochondria which would explain their common alteration in Zellweger syndrome.