title: Pathogenic mechanisms of the acute porphyric attack: speculative roles of manganese associated enzymes.
abstract: 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.
authors.affiliation: Porphyria Centre Sweden, S:t Göran Hospital, Stockholm, Sweden.
authors.forename: S
authors.initials: S
authors.lastname: Thunell
authors.forename: Y
authors.initials: Y
authors.lastname: Floderus
authors.forename: P
authors.initials: P
authors.lastname: Harper
authors.forename: A
authors.initials: A
authors.lastname: Henrichson
authors.forename: U
authors.initials: U
authors.lastname: Lindh
authors.forename: S
authors.initials: S
authors.lastname: Marklund
mesh_terms: D000328:Adult; D005260:Female; D005974:Glutamate-Ammonia Ligase / Q000378:metabolism*; D006098:Granulocytes / Q000737:chemistry; D006579:Heterozygote; D006801:Humans; D008297:Male; D008345:Manganese; D008875:Middle Aged; D017118:Porphyria, Acute Intermittent / Q000201:enzymology* / Q000235:genetics; D011766:Pyruvate Carboxylase / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism*
chemical_list: D008345:Manganese; D013482:Superoxide Dismutase; D005974:Glutamate-Ammonia Ligase; D011766:Pyruvate Carboxylase