Theron J J, van Papendorp D H
Department Fisiologie, Fakulteit Geneeskund, Universiteit van Pretoria.
S Afr Med J. 1996 Jun;86(6):685-90.
Peroxisomes are ubiquitous cytoplasmic structures in mammalian tissues. The metabolic functions of these organelles include synthesis of plasmalogens and other ether lipids, beta-oxidation, especially of very long-chain fatty acids (VLCFAs, > C22) and their derivatives, inactivation of hydrogen peroxide by peroxisomal catalase and involvement in several other metabolic pathways, e.g. gluconeogenesis, catabolism of purines and polyamines and detoxification of ethanol. Peroxisomal diseases which may arise from genetic faults in the biogenesis of the organelle or aberrant targeting of one or more proteins to the peroxisome, are divided into three groups based on the extent of loss of peroxisomal functions. Prototype of the first group is the cerebro-hepato-renal syndrome of Zellweger (ZS) which shows generalised loss of peroxisomal functions and absence of demonstrable mature peroxisomes in the liver. Other syndromes which are briefly discussed include neonatal adrenoleukodystrophy (NALD) and infantile Refsum syndrome (IRS) which may be regarded as milder variants of ZS, and diseases caused by loss of a limited number of peroxisomal functions (rhizomelic chondrodysplasia punctate). However, the group of peroxisomal diseases with the highest incidence are those syndromes where only a single peroxisomal function is impaired. The most common peroxisomal disease, X-linked adrenoleukodystrophy (XALD) belongs to this group. XALD develops as a result of an isolated defect of peroxisomal acyl-CoA synthetase with resultant accumulation of VLCFAs, especially C26:0. Primary hyperoxaluria type 1 is caused by deficient activity of peroxisomal alanine: glyoxylate aminotransferase due to aberrant targeting of this enzyme to mitochondria and not peroxisomes, a unique example of a genetic enzyme trafficking defect. The primary diagnosis of these syndromes is usually based on clinical findings and measurement of accumulated or depleted metabolites in the body e.g. VLCFAs, bile acid intermediates, phytanic acid, pipecolic acid and plasmalogens. Therapy includes dietary adjustments e.g. supplementation with oleic acid derivatives to normalise elevated VLCFAs in XALD. Treatment with hypolipidaemic drugs and certain peroxisomal substrates which induce proliferation of mature peroxisomes offers promise in the therapy of these debilitating and often fatal diseases.
过氧化物酶体是哺乳动物组织中普遍存在的细胞质结构。这些细胞器的代谢功能包括缩醛磷脂和其他醚脂的合成、β-氧化，尤其是极长链脂肪酸（VLCFAs，> C22）及其衍生物的β-氧化、过氧化物酶体过氧化氢酶使过氧化氢失活以及参与其他几种代谢途径，例如糖异生、嘌呤和多胺的分解代谢以及乙醇解毒。过氧化物酶体疾病可能源于细胞器生物发生过程中的遗传缺陷或一种或多种蛋白质错误靶向过氧化物酶体，根据过氧化物酶体功能丧失的程度可分为三组。第一组的典型代表是泽尔韦格脑肝肾综合征（ZS），其表现为过氧化物酶体功能普遍丧失且肝脏中未检测到成熟的过氧化物酶体。简要讨论的其他综合征包括新生儿肾上腺脑白质营养不良（NALD）和婴儿型雷夫叙姆综合征（IRS），它们可被视为ZS的较轻变体，以及由有限数量的过氧化物酶体功能丧失引起的疾病（肢根型点状软骨发育不良）。然而，发病率最高的过氧化物酶体疾病组是那些仅单个过氧化物酶体功能受损的综合征。最常见的过氧化物酶体疾病，X连锁肾上腺脑白质营养不良（XALD）属于这一组。XALD是由于过氧化物酶体酰基辅酶A合成酶的孤立缺陷导致VLCFAs，尤其是C26:0积累而发生的。原发性高草酸尿症1型是由于过氧化物酶体丙氨酸：乙醛酸转氨酶活性不足引起的，该酶错误靶向线粒体而非过氧化物酶体，这是遗传酶转运缺陷的一个独特例子。这些综合征的初步诊断通常基于临床表现以及对体内积累或减少的代谢物的测量，例如VLCFAs、胆汁酸中间体、植烷酸、哌可酸和缩醛磷脂。治疗包括饮食调整，例如补充油酸衍生物以使XALD中升高的VLCFAs正常化。用降血脂药物和某些诱导成熟过氧化物酶体增殖的过氧化物酶体底物进行治疗为这些使人衰弱且往往致命的疾病的治疗带来了希望。
