Hepcidin Synthesis

1. Introduction

Hepcidin is a peptide hormone synthesized mainly in the liver and the active form consists of 25 aminoacids. Some studies have demonstrated the relationship between hepcidin and iron. Nicolas et al. observed a severe iron overload in mice that were knockout for the gene encoding hepcidin [1]. It has also been shown that hepcidin is regulated by hemojuvelin, a protein produced in the liver and whose gene expression is responsible for juvenile hemochromatosis, causing excessive accumulation of iron in different organs, mainly in the liver [2] and promoting the development of certain infectious diseases [3]. The maintenance of iron levels involves regulation of iron absorption from the diet and its storage in hepatic and splenic macrophages. During absorption, iron is taken up by enterocytes, where it will bind to ferroportin or be incorporated into intracellular ferritin for storage [4, 5]. Hepcidin has been shown to have its main role in iron homeostasis, as it regulates transmembrane iron transport. It binds to the cell surface receptor, ferroportin, which is then internalized and digested by lysosomes. Ferroportin enables iron flux from enterocytes, hepatocytes, and macrophages into blood. Hence, the decrease in ferroportin levels in enterocytes due to hepcidin action leads to decreased iron absorption in hepatocytes

The fragmentor and collision energy conditions were calculated for [M+4H]4+ m/z 698.1 and m/z 703.2 and [M+5H]5+ m/z 558.7 and m/z 562.8 for hepcidin and the [13C18, 15N3]-hepcidin standard, respectively. These were found to be the most intense ions, in accordance with Bansal et al.[16]. We selected the transitions 698.1 → 86.1 and 562.8 → 70.2 to quantify hepcidin levels in the plasma samples of triathletes. Figure 1 shows the chromatograms of both the 10 nM hepcidin standard and the endogenous hepcidin present in the