Induction of porphobilinogen oxygenase and porphobilinogen deaminase in rat blood under conditions of erythropoietic stress.
Porphobilinogen is the substrate of two enzymes: porphobilinogen deaminase and porphobilinogen-oxygenase. The first one transforms it into the metabolic precursors of heme and the second diverts it from this metabolic pathway by oxidizing porphobilinogen to 5-oxopyrrolinones. Rat blood is devoid of porphobilinogen-oxygenase under normal conditions while it carries porphobilinogen-deaminase activity. When the rats were submitted to hypoxia (pO2 = 0.42 atm) for 18 days, the activity of porphobilinogen-oxygenase appeared at the tenth day of hypoxia and reached the maximum at the 14-16th day. It decreased to a half after 2 days (half-life of the enzyme) and disappeared after 4 days of return to normal oxygen pressure. Porphobilinogen-deaminase activity increased after the first day of hypoxia, reached a maximum at the 14-16th day and did not decrease to normal values until the 15th day after return to normal oxygen pressure. The activities of both porphobilinogen-oxygenase and porphobilinogen-deaminase were induced by administration of erythropoietin. When rats were made anaemic with phenylhydrazine, porphobilinogen-oxygenase activity also appeared in the blood cells. Although the reticulocyte concentration was higher when compared to that obtained under hypoxia, the activities of the oxygenase obtained under both conditions were comparable. Porphobilinogen-deaminase activity was always closely related to the reticulocyte content. The appearance of porphobilinogenase-oxygenase under the described erythropoietic conditions was due to a de novo induction of the enzyme, as shown by its inhibition with actinomycin D and cycloheximide. Porphobilinogen-oxygenase as well as porphobilinogen-deaminase were present in the rat bone marrow under normal conditions. Their activities increased in phenylhydrazine treated rats. The properties and kinetics of porphobilinogen-oxygenase from the rat blood and bone marrow were determined and found it differ in several aspects.
D000642:Ammonia-Lyases / Q000097:blood*; D000818:Animals; D001853:Bone Marrow / Q000201:enzymology*; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D004920:Erythropoiesis; D004921:Erythropoietin / Q000494:pharmacology; D005260:Female; D006207:Half-Life; D011163:Hydroxymethylbilane Synthase / Q000096:biosynthesis / Q000097:blood*; D000860:Hypoxia / Q000097:blood*; D007700:Kinetics; D006899:Mixed Function Oxygenases / Q000096:biosynthesis / Q000097:blood; D010659:Phenylhydrazines / Q000494:pharmacology; D011162:Porphobilinogen / Q000096:biosynthesis / Q000097:blood; D051381:Rats
D010659:Phenylhydrazines; D004921:Erythropoietin; D003609:Dactinomycin; D011162:Porphobilinogen; D003513:Cycloheximide; D006899:Mixed Function Oxygenases; C022429:porphobilinogen oxygenase; D011163:Hydroxymethylbilane Synthase; D000642:Ammonia-Lyases