Molecular aspects of the inherited porphyrias

Abstract

. Sassa S, Kappas A (The Rockefeller University, New York, USA). Molecular aspects of the inherited porphyrias (Review). J Intern Med 2000; 247: 169–178. The porphyrias are diseases due to marked deficiencies of enzymes of the haem biosynthetic pathway ( Fig. 1). Except for the first enzyme of the pathway, δ‐aminolevulinate synthase (ALAS), deficiencies in seven other enzymes are associated with the various forms of porphyria ( Fig. 2). Porphyrias can be classified as either hepatic or erythroid, depending on the major site of production of porphyrins or their precursors. The pathogenesis of all inherited porphyrias has now been defined at the molecular level, and it is clear that there is a great deal of genetic heterogeneity in each porphyria [1]. 1 Structure of major porphyrins: (a) uroporphyrin III; (b) corpoporphyrin III; (c) protoporphyrin IX. 2 Diseases due to enzymatic deficiency of the haem biosynthetic pathway. XLSA, X‐linked sideroblastic anaemia; Zn‐PP, zinc protoporphyrin IX; Free PP, free protoporphyrin IX; 7‐C porphyrin, 7‐carboxylate porphyrin. Other abbreviations are defined in the text.

Danos ao DNA promovidos por ácido 5-aminolevulínico: possível associação com o desenvolvimento de carcinoma hepatocelular em portadores de porfiria aguda intermitente

“…Esta deficiência resulta na produção excessiva e excreção de porfirinas e de seus precursores [2][3][4][5][6] . As porfirias são tradicionalmente classificadas com base no principal órgão que produz os metabólitos porfíricos em excesso (fígado ou os tecidos eritropoiéticos), na ocorrência ou não de ataques agudos e nas lesões cutâneas (fotossensibilidade) e/ou neurológicas produzidas 5,7,8 .…”

“…A porfiria aguda intermitente também denominada porfiria sueca, pirroloporfiria e porfiria intermitente aguda 5,27 é uma desordem hereditária autossômica dominante, relativamente rara, mas que é encontrada em diversas populações 8 . Nos Estados Unidos, a incidência do defeito gênico afeta entre 5-10 em cada 100 mil indivídu-os e na Austrália 3 em 100 mil 28 .…”

Computational Characterization of the Substrate-Binding Mode in Coproporphyrinogen III Oxidase

“…Deficient activity of coproporphyrinogen III oxidase causes the accumulation and non-enzymatic oxidation of coproporphyrinogen, leading to neurological disturbances and skin photosensitivity 8 . The enzyme functions as a dimer in solution, and both the human 9 and yeast 10 enzymes have been crystallized and solved at good resolutions (2.0 Å for the yeast enzyme, and 1.58 Å for the human variant).…”

Seeing purple

“…Schultz's 33 year old weaver with "pemphigus leprosus" 34 had endured skin sensitivity from infancy, was found to have splenomegaly, and passed wine-red urine 37 (porphyrinuria), typical of congenital erythropoietic porphyria in which red urine may be noticed shortly after birth. 38 In contrast, Hipprocates' patient may have had an acute hepatic porphyria as she suffered frequent great pains, delirium, agitation, spasms, sweating and coma before her menses, and she also passed dark urine. 39 The chemical studies that led to the discovery of the porphyrias started simply enough in 1841 when Johann Joseph von Scherer described an iron-free residue that he had extracted from blood using concentrated sulfuric acid.…”