Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.5.1.61 (porphobilinogen deaminase)
 637 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Erythropoietin (Epo) is an unambiguous inducer of red cell differentiation in mammals. Purified Epo, derived from urine of anemic patients, is a glycoprotein of molecular weight about 34,000. There are two forms with the same biological activity and amino acid composition but with differing carbohydrate compositions. All of the carbohydrate is in the form of N-linked complex oligosaccharides. Erythropoietin appears to contain three domains, two protease-resistant regions containing all of the carbohydrate, connected by a protease-sensitive region containing the active site. Cells derived from mice infected with the anemia variant of the Friend leukemia, bind Epo specifically. The receptors have a dissociation constant of about 5 nM and there are only 600-700 per cell. Erythropoietin has a rapid effect on the transcription and processing of the globin genes. Among the enzymes of heme synthesis, it has an early effect only on uroporphyrinogen synthase. Studies with Epo and colony-stimulating factor (CSF) suggest that these inducers compete for the same, or very closely related cells of the hemopoietic system. When marrow cells are put into close apposition by centrifugation, their responses to Epo and CSF and the competitive actions of these inducers increase.
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PMID:Erythropoietin and its mode of action. 610 Apr 37

Mouse bone marrow cells infected in vitro with the anemia strain of Friend leukemia virus from large clusters (bursts) of erythroblasts after 5 days in culture in methylcellulose medium. Two types of erythroblast populations can be isolated from bursts of infected cells by manipulation of the culture conditions. One type of erythroblast, which is obtained when erythropoietin (EP) is added to the culture, has proliferated and undergoes differentiation to become an erythrocyte. The second type of erythroblast, which is obtained when no EP is added to the culture, is the product of extensive proliferation, but it fails to undergo the terminal stages of erythroblast differentiation. Comparisons of these two types of erythroblasts demonstrate that specific EP effects include changes in the nucleus, cytoplasm, and membrane of the treated cells. Those events of erythroid differentiation shown to be directed by EP were extrusion of the nucleus from the erythroblast, induction of uroporphyrinogen I synthetase activity, increased iron incorporation into protoporphyrin, synthesis of alpha- and beta-globin polypeptides due largely to increased mRNA production, and synthesis and incorporation of spectrin into the cell membrane. In this system, EP promotes these effects without observable stimulation of progenitor proliferation in addition to that caused by the virus alone. Thus, the role of EP in terminal erythrocyte differentiation is not simply that of an erythroid-specific mitogen.
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PMID:Specific differentiation events induced by erythropoietin in cells infected in vitro with the anemia strain of Friend virus. 695 15