Year: 1993
Type: dissertation
Abstract: The aim of the work described in this thesis was to examine further the mechanisms\ninvolved in the accumulation of uroporphyrins in the liver, i.e., the role of iron and an\nincreased activity of one of the preceding enzymes in the heme biosynthetic pathway,\nPBG-D, in the porphyrinogenic process in experimental uroporphyria and in PCT.\nIn the previous paragraphs, the proposed role of iron in the development of\nuroporphyria has been discussed. However, a study on the time-sequence relationship\nbetween iron accumulation and uroporphyrin production in the liver has not been\nperformed. In addition, the nature of the iron pool involved in this process has not been\nestablished. The role of iron in uroporphyria has been explained by its ability to\nparticipate in peroxidative and free radical reactions. Desferrioxamine, an iron chelator,\nhas been described to diminish uroporphyrin accumulation in the liver. At present, the\nspecific effects of desferrioxamine on iron accumulation, free radical-mediated reactions,\nuroporphyrin accumulation and URO-D activity in the liver have not been studied in\nexperimental uroporphyria.\nIt has been reported that the activity of the enzyme PBG-D is increased in erythrocytes\nand livers of patients with PCT. It is not clear whether this increased PBG-D activity can\nbe observed both in animals with experimental uroporphyria and in humans with sporadic\nand familial forms of PCT. An increased PBG-D activity could explain the absence of\nacute attacks in PCT. Moreover, an increased PBG-D activity could also provide an\nadditional explanation for uroporphyrin accumulation in experimental and human uroporphyria.
Author: Peter D. Siersema
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W1699962615