The activities of uroporphyrinogen synthetase and cosynthetase in congenital erythropoietic porphyria (cep)

Abstract

Normal or increased amounts of series III porphyrins with greater amounts of series I were observed on incubation of PBG in hemolysates of congenital erythropoietic porphyria vs. normal erythrocytes, human or bovine. Correlation with reticulocyte percentage was poor, in the aggregate a general trend toward increased values of both isomers I and III was noted with increasing reticulocytes. When the percent of type III was low the net amount was increased as compared with normal. Hemolysates of non-porphyric, reticulocyte-rich red cells (hemolytic or posthemorrhagic anemia) formed only minute amounts of type I porphyrin but at the same time no more, or even less type III than the porphyric hemolysates, although representing red cells of greater reticulocyte content. No evidence of deficient heme synthesis was observed in porphyric hemolysates incubayed with [14C]-porphobilinogen or 59Fe. Other studies of porphyric hemolysates incubated with and without added mouse spleen synthetase failed to reveal evidence of an absolute UPG-III cosynthetase (Co-S) deficiency. The large increases of type I porphyrin with normal or increased formation of type III, both in the disease and in the hemolysates, are believed due to a primary increase of ALA-S or UPG-S activity rather than a decrease of Co-S. Possible mutations which might be responsible for this increase are considered.

Biochemical Diagnosis of a Fatal Case of Günther’s Disease in a Newborn with Hydrops Foetalis

“…The pattern of porphyrin overproduction in congenital erythropoietic porphyria indicates that the block in the haem synthetic pathway occurs at the level of uroporphyrinogen III synthase (3,(20)(21)(22)(23)(24)(25). This enzyme catalyses the formation of uroporphyrinogen III from hydroxymethylbilane or from porphobilinogen if porphobilinogen deaminase is present (2).…”

Experimental protoporphyria in hairless mice: An animal model for photodynamically induced dermatitis

“…Congenital Erythropoietic Porphyria is also observed in pigs (Joergenson et al, 1963 It is assumed that in this type of porphyria the metabolic defect in the erythroid cells involves a reductiQn of the uroporphyrinogen-III-cosyntase activity (Romeo et al, 1970;Flyger et al, 1977) probably combined with an increase in uroporphyrinogen-I-syntase activity (Miyagi et al, 1976;Moore et al, 1978).…”

Liver Transplantation in Acute Hepatic Porphyria and Erythropoietic Protoporphyria

“…In AIP symptom relapse, hepatic PBGD activity was shown to be reduced below the activity seen in remission, whereas the erythrocyte enzyme activity remained unchanged. 102,103 The structural basis for reduced hepatic PBGD activity during the acute attack has been traced to post-translational steps involving the assembly of the dipyrromethane cofactor. 104 During an acute attack, PBG concentrations are sufficiently high to prevent formation of active holoenzyme PBGD.…”