Studies on Porphyrin Biosynthesis and the Enzymes Involved in Bovine Congenital Erythropoietic Porphyria

Abstract

1. Porphyrin biosynthesis and the enzymes succinyl-CoA synthetase (EC 6.2.1.5), δ-aminolaevulinate synthase (EC 2.3.1.37), δ-aminolaevulinate dehydratase (EC 4.2.1.24) and porphobilinogenase enzyme complex at 37°C and 45°C were studied in blood, bone marrow, spleen, liver and kidney of normal bulls and a bull with congenital erythropoietic porphyria (CEP). 2. Biosynthesis by erythrocytes and spleen was low and slightly lower in CEP than in the normal animals. In liver and kidney biosynthesis was somewhat higher and still lower in CEP than in normal animals. In bone marrow it was high and considerably higher in CEP than in normal animals. In all tissues biosynthesis was higher from porphobilinogen than from δ-aminolaevulinic acid. 3. The porphyrin biosynthesis pattern was 40% uroporphyrin, 15% heptacarboxylic porphyrin, 25% coproporphyrin and 20% suburoporphyrin in the normal animals, but in CEP it was 50% uroporphyrin I, 20–30% uroporphyrin III, 10–12% heptacarboxylic porphyrin and 10–20% suburoporphyrin. 4. In CEP gall-bladder bile contained 100 μmol of coproporphyrin/l and the fresh bladder urine 9 μmol/l, which on standing increased to 21 μmol/l, pointing to excretion of most porphyrin as porphyrinogen in the urine. The blood plasma contained only traces of porphyrin. 5. Enzyme determinations showed threefold increased succinyl-CoA synthase in CEP bone marrow as compared with normal animals, many-fold increase of aminolaevulinate synthase, normal aminolaevulinate dehydratase, sevenfold increase of porphobilinogenase activity on incubation at 45°C and threefold increase at 37°C. In blood, aminolaevulinate synthase and aminolaevulinate dehydratase were increased in CEP, whereas porphobilinogenase at 45 °C was reduced. In liver, aminolaevulinate synthase was normal and porphobilinogenase decreased. 6. Our results show that in this animal with CEP there was an increased porphobilinogen deaminase and a significant enhancement of aminolaevulinate synthase concomitant with a diminished activity of uroporphyrinogen III cosynthase.