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Erythropoietin: definition, structure, synthesis in vivo

Definition:

EPO: = erythropoietin  
A glycoprotein hormon-like structure, a sialoglycoprotein, which is an important factor in the survival, growth and proliferation of erythroid precursor cells (EPC) and it improves the de novo creation, differentation and growth of red blood cells (RBC).
Thus, EPO controls the erythropoiesis = production of RBC.

 EPC: these are cells that are located in the bone marrow, will eventually form the RBC.
RBC: cells responsible for the transport and distribution of oxygen throughout the body.

 Structure:

 Built out of 165 aminoacids (AA). They are all connected and form 1 polypeptide chain. 
Although, within the chain, there are 2 disulfide bonds. 
Respectively on positions: Cys7-161 and Cys29-33 
Cys = cystein and the numbers indicate the positions these AA are located.
Cystein structure. Available sulfide group for bonding
There are also 4 positions where there is a possibility for glycosylation 
Namely: 3 N-linked: Asn24, Asn38, Asn83; en 1 O-linked: Ser126. On these positions, carbohydrates can bond on the EPO structure.

 EPO has an estimated molecular weight of 36 kDa (kilodalton); but, the polypeptide chain itself is only 18 kDa. This means that the other weight is made out of the bonded carbohydrates. 
EPO AA structure
Synthesis in the body:

 EPO is formed in the kidney, more specific in the renal perituberal interstitial cells as an answer to hypoxia (a shortage of oxygen in the body/body parts).
It is also formed in the liver, but more so in the early stages of life, the kidney will takeover most production during adulthood.
The concentration of EPO in circulation of the body is relatively low in homeostasis, and is regulated with a feedback system directly associated with blood oxygenation. Although, during anemia or hypoxia, the concentration and secretion of EPO can increase up to a 1000-fold! 

 EPO is secreted in the urine.

 Effect of glycosylation:

 In vitro activity of glycosylated EPO and non-glycosylated EPO is the same.
But! In vivo activity is not.
In vivo non-glycosylated EPO has almost no activity. Glycosylated EPO is more active. Also, the more sialic acids that are placed on the EPO protein, the longer it stays in the body and stays active: these sialic acid residu's protect EPO from binding to a binding lectin in the liver that degrades the EPO.

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