The binding mode and promotive effects of iron bioavailability

Introduction

Iron is an essential micronutrient for human beings, existing in the form of non-heme or heme iron, which is also an important constituent of multiple proteins as an organic or inorganic cofactor (Pantopoulos, Porwal, Tartakoff, & Devireddy, 2012). In biological systems, iron is present in one of two oxidation states. The redox interconversions of the ferrous and ferric forms are central to the biological properties of this element, with the ferric ion being less soluble in water than ferrous ion (Lopez & Martos, 2004). Iron possesses a wide variety of biological functions due to its vital biochemical activities, such as oxygen transport, energy production and cellular proliferation (Vukosav, Mlakar, & Tomisic, 2012). Iron losses or insufficient iron absorption from dietary sources can cause iron deficiency, which adversely affects human health, leading to microcytic anemia, energy metabolism dysfunction, and immune injury (Guo et al., 2014, Silva and Faustino, 2015). In order to combat iron deficiency, different kinds of iron supplements have been developed. Recently, studies of functional and nutraceutical foods as iron supplements experienced a noticeable increase in applications of preventing diseases and improving health (Diego Quintaes et al., 2017, Fairweather-Tait and Teucher, 2002, Kajarabille et al., 2017). Among different kinds of iron supplements, food fortification by addition of iron in the form of iron-peptide complexes has been proposed to combat iron deficiency, with the advantages of good bioavailability, high absorbability, excellent stability and high safety (Caetano-Silva et al., 2015, Prentice et al., 2017, Tolkien et al., 2015). In order to develop iron supplements by addition of iron-peptide complexes, different iron-chelating peptides have been purified and identified from various kinds of protein sources, such as Pacific cod (Wu, Li, Hou, Zhang, & Zhao, 2017), anchovy (Wu, Liu, Zhao, & Zeng, 2012), barley (Eckert et al., 2016), chickpea (Zhang, Li, Miao, & Jiang, 2011), egg (Liu, Oey, Bremer, Carne, & Silcock, 2018) and casein (Miao et al., 2019).

Recently, several iron-chelating peptides have been further studied for structure-activity relationship. The process of iron-peptide chelation has been interpreted by different instrumental analysis through the information from changes before and after iron-peptide chelation reaction. The formation, stoichiometry and speciation of complexes involving mineral ions and organic ligands are examined by electrospray ionization mass spectrometry (ESI-MS) (Keith-Roach, 2010). A wealth of information on structure and environment of the protein backbone and amino acid side chain is supplied by fourier transform infrared (FTIR) spectroscopy (Barth, 2000). The secondary structure and conformational changes of peptides are determined by circular dichroism spectroscopy (Guler, Vorob'ev, Vogel, & Mantele, 2016). In addition, the surface charge state of particles in dispersion systems (Sun et al., 2017), the stability constants of peptides and their complexes with mineral ions (Wang, Wang, Li, & Li, 2014) as well as the electron cloud density around hydrogen nucleus in the peptide changed (Zhao et al., 2014) also play an important part in the analysis of iron-peptide complexes. However, the information about structure-activity relationship plays an essential role in explaining and confirming the high chelating activity of peptides, which also lays foundation for the study of iron uptake and transport.

Nowadays, researchers also paid increasing attention to iron bioavailability improved by iron-chelating peptides, involving effects of chelating peptides on iron uptake and transport as well as molecular mechanism of iron-chelating peptides improving iron uptake and transport. Among iron-chelating peptides, caseinophosphopeptides (CPPs) have caught particular concern (Bougle and Bouhallab, 2017, Bouhallab and Bouglé, 2004, Delshadian et al., 2018). Garcia-Nebot, Barbera, and Alegria (2013) found that the CPPs group showed an increase of ferritin synthesis in Caco-2 cells versus the iron sulphate group. In the study conducted by Ait-Oukhatar et al. (2002), CPPs were reported to be able to bind and solubilize iron, which prevented the formation of high molecular weight ferric hydroxides. As a result, β-CN(1-25)-Fe showed better absorption and tissue uptake by the vascularized rat loop model compared with ferric ascorbate.

All in all, iron-chelating peptides showed a potential as novel carriers to combat iron deficiency (Ma et al., 2019). As a result, many studies have been conducted on iron supplements in the form of iron-chelating peptides (Sun et al., 2017, Walters et al., 2018, Wu et al., 2017). Previous reviews about mineral chelating peptides were mainly focused on food protein sources and purification approaches used for the generation of chelating peptides, strategies for the discovery and identification of chelating peptides as well as measurement of mineral chelating activity (Nongonierma and FitzGerald, 2017, Tu et al., 2018). In our previous review about calcium-chelating peptides, the sources of food-derived calcium-chelating peptides, the calcium-peptide binding mode as well as calcium absorption and bioavailability enhancement potential of chelating peptides have been concluded and discussed (Sun et al., 2016). Recently, many useful results have been obtained from studies of iron-chelating peptides, especially in fields of the molecular nature of iron-peptide chelation and iron bioavailability affected by chelating peptides. However, up to now, the review, focusing on the latest progress of iron-chelating peptides, has not been published. It is necessary to present a review about iron-chelating peptides in order to outline the possible iron-peptide binding mode and promotive effects of iron bioavailability by chelating peptides, which can supply research progresses on iron-chelating peptides for readers as well as a direction for future studies.

Section snippets

Structure-activity relationship of iron-chelating peptides

The structural characteristic of iron-chelating peptides exerts an important influence on the chelating activity and binding mode of peptides with iron. The newly identified iron-chelating peptides with different structural characteristic are listed in Table 1. In order to make clear the structure-activity relationship of iron-chelating peptides, instrumental analysis has been applied, which can interpret the interaction between chelating peptide and iron.

Effects of iron-peptide complexes on the improvement of iron bioavailability

Many factors are related to the effect of iron-peptide complexes on the improvement of iron bioavailability. During the digestion in gastrointestinal tract, the stability of iron-peptide complexes is of importance. Additionally, iron uptake, transport and retention as well as ferritin concentration in several models, involving cell, animal and human, are often used to evaluate the promotive effects of iron-peptide complexes on iron bioavailability. At last, pathways, used by iron-chelating

Conclusions and future trends

Recently, chelating peptides have aroused wide interest of researchers. As the dietary iron plays an important role in human health, studies on iron-chelating peptides are increasing. Some detailed information about newly identified iron-chelating peptides was gradually clear. This review outlined current developments associated with researches in iron-chelating peptides. Compared with other reviews about chelating peptides, this review was mainly about iron fortification, including

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Acknowledgements

This work was financially supported by the Doctoral Startup Fund by Science and Technology Bureau of Liaoning Province (Nos. 2019-BS-017 and 201601269).