thesis
The liver in uroporphyria : a biochemical and morphological study
- Publication date
- 27 October 1993
- Publisher
- The aim of the work described in this thesis was to examine further the mechanisms
involved in the accumulation of uroporphyrins in the liver, i.e., the role of iron and an
increased activity of one of the preceding enzymes in the heme biosynthetic pathway,
PBG-D, in the porphyrinogenic process in experimental uroporphyria and in PCT.
In the previous paragraphs, the proposed role of iron in the development of
uroporphyria has been discussed. However, a study on the time-sequence relationship
between iron accumulation and uroporphyrin production in the liver has not been
performed. In addition, the nature of the iron pool involved in this process has not been
established. The role of iron in uroporphyria has been explained by its ability to
participate in peroxidative and free radical reactions. Desferrioxamine, an iron chelator,
has been described to diminish uroporphyrin accumulation in the liver. At present, the
specific effects of desferrioxamine on iron accumulation, free radical-mediated reactions,
uroporphyrin accumulation and URO-D activity in the liver have not been studied in
experimental uroporphyria.
It has been reported that the activity of the enzyme PBG-D is increased in erythrocytes
and livers of patients with PCT. It is not clear whether this increased PBG-D activity can
be observed both in animals with experimental uroporphyria and in humans with sporadic
and familial forms of PCT. An increased PBG-D activity could explain the absence of
acute attacks in PCT. Moreover, an increased PBG-D activity could also provide an
additional explanation for uroporphyrin accumulation in experimental and human uroporphyria.