Porphyrin-induced protein structural alterations of heme enzymes II: protection of 5-aminolevulinic acid dehydratase and porphobilinogen deaminase from the photodynamic and non-photodynamic effects of URO and PROTO

Afonso, Susana

doi:10.1016/s1357-2725(97)00099-x

Cited by 6 publications

(7 citation statements)

References 18 publications

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“…Even though sulfhydryl groups are not involved in the formation of molecular aggregates, URO I as well as PROTO IX affect these groups, although differently, and their action is not directly related to enzyme inactivation. The presence of sulfhydryl reagents during exposure of the enzymes to URO I or PROTO IX confirmed these findings and indicated that porphyrins may affect sulfhydryl groups at the active site of ALA-D and PBG-D (51).…”

Section: Molecular Alterations Induced By Porphyrinssupporting

confidence: 54%

“…Mixtures of albumin and pure ALA-D or PBG-D were exposed to URO I or PROTO IX in the dark or under UV light. Electrophoresis of these reaction mixtures did not show protein bands other than those of the controls (50,51).…”

Section: Molecular Alterations Induced By Porphyrinsmentioning

confidence: 69%

“…Electrophoresis of these preparations in the presence of SDS and 8 M urea showed the same bands of high molecular weight. Instead, electrophoresis of samples treated with ß-mercaptoethanol or dithiothreitol, before or after exposure of the enzymes to porphyrins, did not show the appearance of those bands (51). These results indicate that molecular aggregates may not be due to formation of disulfide bridges, but rather to covalent binding.…”

Section: Molecular Alterations Induced By Porphyrinsmentioning

confidence: 78%

“…Nucleophilic addition of hydroxylamine to ALA-D and PBG-D before their exposure to porphyrins did not prevent the direct effect of URO I and PROTO IX on the proteins in the dark, but it did protect the enzymes from photoinactivation (51). Electrophoresis of these systems did not demonstrate the appearance of molecular aggregates (51), confirming the postulated mechanism of porphyrin-photoinduced cross-linking (6).…”

Section: Molecular Alterations Induced By Porphyrinsmentioning

confidence: 79%

“…However, blockage of amino groups before treatment with URO I or PROTO IX partially protected the enzyme activities, and the electrophoretograms did not reveal the presence of high molecular weight bands. So, free amino groups may be involved in the porphyrin-photoinduced cross-linking, but may not be implicated in the effect of URO I and PROTO IX in the dark (51).…”

Section: Molecular Alterations Induced By Porphyrinsmentioning

confidence: 99%

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The photodynamic and non-photodynamic actions of porphyrins

Afonso

Salamanca

Batlle

1999

Braz J Med Biol Res

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Porphyrias are a family of inherited diseases, each associated with a partial defect in one of the enzymes of the heme biosynthetic pathway. In six of the eight porphyrias described, the main clinical manifestation is skin photosensitivity brought about by the action of light on porphyrins, which are deposited in the upper epidermal layer of the skin. Porphyrins absorb light energy intensively in the UV region, and to a lesser extent in the long visible bands, resulting in transitions to excited electronic states. The excited porphyrin may react directly with biological structures (type I reactions) or with molecular oxygen, generating excited singlet oxygen (type II reactions). Besides this well-known photodynamic action of porphyrins, a novel light-independent effect of porphyrins has been described. Irradiation of enzymes in the presence of porphyrins mainly induces type I reactions, although type II reactions could also occur, further increasing the direct non-photodynamic effect of porphyrins on proteins and macromolecules. Conformational changes of protein structure are induced by porphyrins in the dark or under UV light, resulting in reduced enzyme activity and increased proteolytic susceptibility. The effect of porphyrins depends not only on their physico-chemical properties but also on the specific site on the protein on which they act. Porphyrin action alters the functionality of the enzymes of the heme biosynthetic pathway exacerbating the metabolic deficiencies in porphyrias. Light energy absorption by porphyrins results in the generation of oxygen reactive species, overcoming the protective cellular mechanisms and leading to molecular, cell and tissue damage, thus amplifying the porphyric picture.

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Section: Molecular Alterations Induced By Porphyrinssupporting

confidence: 54%

Section: Molecular Alterations Induced By Porphyrinsmentioning

confidence: 69%

Section: Molecular Alterations Induced By Porphyrinsmentioning

confidence: 78%