Thunell S, Andersson C, Carlmark B, Floderus Y, Grönqvist S O, Harper P, Henrichson A, Lindh U
Porphyrias Service Sweden, Stockholm, Sweden.
Eur J Clin Chem Clin Biochem. 1995 Apr;33(4):179-94. doi: 10.1515/cclm.1995.33.4.179.
Previously symptomatic and permanently asymptomatic carriers of a gene mutation for acute intermittent porphyria as well as matched controls were screened with regard to a series of variables of possible relevance to the development of porphyric symptoms. The basis for the study was a concept of acute porphyria as a condition of a permanent system overload of oxidative stress, with long term effects on hepatic and renal tissue, and with instances of periodic overload of free radicals giving rise to acute neurologic involvement. Leukocyte concentrations of manganese, calcium, iron and zinc, as well as erythrocyte calcium differed between the groups, acute intermittent porphyria gene carriers, irrespective of previous porphyric illness, showing significantly higher levels than the controls. Manganese was found to be the most discriminative component of all the 78 variables investigated, accounting for about 98 per cent of the variance between the groups. An increment, by a factor of four, in cellular manganese is suggestive of an increase, in acute intermittent porphyria, of a manganese associated enzyme, e.g. glutamine synthetase, pyruvate carboxylase or mitochondrial superoxide dismutase. The best fit into the model considered is provided by a theory focused on superoxide dismutase, induced in response to superoxide anion radical produced from aminolaevulinic acid. In porphyria gene carriers seemingly resistant to porphyric manifestations, an increase in potentially prooxidant cellular iron is matched by a proportional increment in manganese, i.e. presumably by a corresponding mitochondrial superoxide dismutase induction. This mechanism is not operative in porphyric individuals prone to development of neuropsychiatric symptoms. In acute intermittent porphyria with a history of porphyric illness there is a positive correlation between erythrocyte manganese and serum folate and a negative correlation between leukocyte ferrochelatase activity and serum cobalamin concentration. This may mirror a role of the cobalamin-folate system in the acute porphyric process.
对急性间歇性卟啉病基因突变的既往有症状和永久无症状携带者以及匹配的对照组进行了一系列可能与卟啉症状发展相关变量的筛查。该研究的基础是将急性卟啉病视为一种氧化应激永久系统过载的疾病，对肝和肾组织有长期影响，且自由基的周期性过载会导致急性神经受累。两组之间白细胞中锰、钙、铁和锌的浓度以及红细胞钙存在差异，急性间歇性卟啉病基因携带者，无论既往有无卟啉病病史，其水平均显著高于对照组。在所有研究的78个变量中，锰是最具区分性的成分，占两组间差异的约98%。细胞内锰增加四倍表明在急性间歇性卟啉病中，与锰相关的酶如谷氨酰胺合成酶、丙酮酸羧化酶或线粒体超氧化物歧化酶增加。最符合所考虑模型的是一种聚焦于超氧化物歧化酶的理论，该酶是由氨基乙酰丙酸产生的超氧阴离子自由基诱导产生的。在似乎对卟啉表现有抵抗力的卟啉病基因携带者中，潜在促氧化细胞铁的增加与锰的相应增加相匹配，即可能是由相应的线粒体超氧化物歧化酶诱导所致。这种机制在易出现神经精神症状的卟啉病个体中不起作用。在有卟啉病病史的急性间歇性卟啉病中，红细胞锰与血清叶酸呈正相关，白细胞铁螯合酶活性与血清钴胺素浓度呈负相关。这可能反映了钴胺素 - 叶酸系统在急性卟啉病过程中的作用。
