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from Greek: ἐρυθρός ("erythros") - red and ποιεῖν ("poiein") - make
Synonyms: Hematopoietin, hemopoietin, EPO
Trade names: Anfoe®, Celpoietin®, Ceriton®, Cresp®, Epofer®, Epofit®, Epomine®, Eporise®, Eposis®, Epotin®, Epotop®, Epotrust®, Epox®, Eprex®, Erypro®, ESA®, Hemax®, LG Espogen®, NeoRecormon®, Relipoietin, RPO®, Shanpoietin®, Vintor®, Wepox®, Zyrop®
German: Erythropoetin

1 Definition

Erythropoietin is a glycoprotein hormone that regulates the production of erythrocytes from precursor cells in the bone marrow (erythropoiesis). It is part of the group of cytokines.

2 Biochemistry

2.1 Structure

From chemistry’s perspective, human erythropoietin is a polypeptide of 165 amino acids. The molecular mass is app. 34 kDa. The secondary structure consists of four α-helices with neighboring loops. The proportion of carbohydrates is around 40% of total molecular mass. It comprises one O-glycosidically bound (Ser 126) and three N-glycosidically bound (Asn 24, Asn 38 and Asn 83) side chains.

2.2 Place of synthesis

In adults, erythropoietin mainly, i.e. 85-90%, is produced in the kidney, more exactly, in the endothelial cells of the peritubular capillaries. Smaller amounts (10-15%) are also synthesized in the liver cells hepatocytes). The ration in a fetus is inverse. Here, the liver is the primary site of the erythropoietin synthesis. However, shortly after birth, the production is reduced. There’s also small-scale erythropoietin synthesis in other organs such as the brain, the uterus, the testicles, and the spleen. The hormone reaches its sites of action via the bloodstream.

2.3 Synthesis

The stimulus for the production of erythropoietin is reduced oxygen saturation (hypoxia) in the renal arteries. It leads to a shift of the α-subunit of the "hypoxia-inducible factor" (HIF) from the cytoplasm to the nucleus of the EPO-expressing cells.

In the nucleus, HIF-α binds to its according β-subunit (HIF-β), which induces the formation of the completed heterodimer HIF-1. HIF-1 binds to CREB and another transcription factor, p300. This results in a complex of 3 protein components that induces the transcription into the related mRNA by binding to the 3'-end of the EPO gene. Then, the translation into the erythropoietin protein takes place in the ribosomes.

The recombinant erythropoietin used for drug therapy is genetically engineered.

3 Physiology

After erythropoietin has been released into the bloodstream, it binds to the erythropoietin receptors in the bone marrow on the membrane of erythroblasts, which leads to a division and maturation of the cells.

4 Laboratory diagnostics

The erythropoietin level can be determined in the course of the extended anemia diagnostics. This is indicated for example in patients on dialysis.

5 Pathophysiology

In advanced renal failure, the kidneys don’t synthesize enough erythropoietin, which subsequently leads to renal anemia. Inflammatory mediators such as interleukin-1 and TNF-alpha inhibit the synthetization of EPO in the kidneys and thus can contribute to anemia in chronic diseases.

This page was last edited on 2 June 2016, at 10:26.

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