Figure 2.

Erythropoiesis feedback system regulated by erythropoietin: when the oxygen supply is reduced, a decrease in oxygen is registered in the kidneys; the breakdown of HIF a is in-hibited by the hypoxia. This inhibition comes about by hydroxylation of HIF a in the peri-tubular fibroblasts by oxygen dependent proline hydrolase. The hydroxylated HIF a is de-graded in binding to the VHL protein. As a result, more erythropoietin is produced, leading to increased erythrocyte production in the bone marrow. The same conditions can be achieved by exogenous supply of erythropoietin. The system is regulated by the resulting negative feedback (PHD, prolyl hydroxylase; HIF, hypoxia inducible factor; VHL, von Hippel-Lindau).