红细胞生成应激条件下大鼠血液中胆色素原氧化酶和胆色素原脱氨酶的诱导作用。

Induction of porphobilinogen oxygenase and porphobilinogen deaminase in rat blood under conditions of erythropoietic stress.

作者信息

Tomaro M L, Frydman R B, Gutnisky A, Sburlati A

出版信息

Biochim Biophys Acta. 1981 Aug 5;676(1):31-42. doi: 10.1016/0304-4165(81)90006-4.

Abstract

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.

摘要

胆色素原是两种酶的底物

胆色素原脱氨酶和胆色素原加氧酶。第一种酶将其转化为血红素的代谢前体，第二种酶则通过将胆色素原氧化为5-氧代吡咯啉酮使其偏离该代谢途径。在正常情况下，大鼠血液中没有胆色素原加氧酶，但具有胆色素原脱氨酶活性。当大鼠处于低氧状态（pO2 = 0.42个大气压）18天时，胆色素原加氧酶的活性在低氧第10天出现，并在第14 - 16天达到最大值。2天后其活性降至一半（该酶的半衰期），恢复正常氧压后第4天消失。胆色素原脱氨酶活性在低氧第1天之后增加，在第14 - 16天达到最大值，直到恢复正常氧压后第15天才降至正常值。给予促红细胞生成素可诱导胆色素原加氧酶和胆色素原脱氨酶的活性。当用苯肼使大鼠贫血时，血细胞中也会出现胆色素原加氧酶活性。尽管与低氧状态下相比，网织红细胞浓度更高，但两种情况下获得的加氧酶活性相当。胆色素原脱氨酶活性始终与网织红细胞含量密切相关。在所描述的造血条件下胆色素原加氧酶的出现是由于该酶的从头诱导，放线菌素D和环己酰亚胺对其的抑制作用证明了这一点。正常情况下大鼠骨髓中存在胆色素原加氧酶和胆色素原脱氨酶。在苯肼处理的大鼠中它们的活性增加。测定了大鼠血液和骨髓中胆色素原加氧酶的性质和动力学，发现它们在几个方面存在差异。