Thunell S, Floderus Y, Harper P, Henrichson A, Lindh U, Marklund S
Porphyria Centre Sweden, S:t Göran Hospital, Stockholm, Sweden.
Cell Mol Biol (Noisy-le-grand). 1997 Feb;43(1):1-8.
The significantly increased concentrations of granulocyte manganese in subjects with AIP may be an indication of overexpression of manganese-associated enzymes. In this study we present further observations related to this phenomenon and speculate that this may provide a rational basis for hypotheses attempting to explain the pathogenesis of the acute attack of porphyria. Such hypotheses are advanced with regard to pyruvate carboxylase, mitochondrial superoxide dismutase and glutamine synthetase, three manganese-dependent enzymes associated with either ALA-generating or ALA-dependent processes. The metabolic impacts in acute porphyria of these enzymes would be functions of the current energy charge of the organism, and would thus explain the protecting and ameliorating effects of glucose in these conditions. Although granulocytes from AIP subjects have elevated manganese concentrations, this did not appear to be associated with increased activities of two enzymes assayed, pyruvate carboxylase or mitochondrial superoxide dismutase. However, enzyme activities in white blood cells do not necessarily represent the levels of catalytic activity in cell types involved in the phenotypic expression of porphyria. Thus it proposed that hypotheses along these new lines of thinking are not flawed by the apparently missing correlations, and should not be therefore discarded. The possible roles of manganese-associated enzymes in the mechanisms behind the acute porphyric attack are discussed in some detail in the paper.
急性间歇性卟啉病（AIP）患者粒细胞锰浓度显著升高，可能表明锰相关酶表达过度。在本研究中，我们展示了与该现象相关的进一步观察结果，并推测这可能为试图解释卟啉病急性发作发病机制的假说提供合理依据。这些假说涉及丙酮酸羧化酶、线粒体超氧化物歧化酶和谷氨酰胺合成酶，这三种与δ-氨基-γ-酮戊酸（ALA）生成或ALA依赖过程相关的锰依赖性酶。这些酶在急性卟啉病中的代谢影响将是生物体当前能量状态的函数，从而解释了葡萄糖在这些情况下的保护和改善作用。尽管AIP患者的粒细胞锰浓度升高，但这似乎与所检测的两种酶（丙酮酸羧化酶或线粒体超氧化物歧化酶）的活性增加无关。然而，白细胞中的酶活性不一定代表参与卟啉病表型表达的细胞类型中的催化活性水平。因此，有人提出，沿着这些新思路的假说不会因明显缺失的相关性而存在缺陷，因此不应被摒弃。本文详细讨论了锰相关酶在急性卟啉病发作背后机制中的可能作用。
