| More than two billion people around the world are affected by Zinc deficiency.This is mainly due to inadequate Zinc intake and inadequate Zinc absorption.Inadequate Zinc absorption is mainly a result of consuming a diet containing high levels of antinutrients such as phytate.Strategies to combat this problem have primarily been through fortification and supplementation using inorganic Zinc salts.However,there have been numerous reports that Zinc salts cause side effects particularly those that affect the gastrointestinal system.Bioactive peptides have the ability to bind with Zinc and aid their transportation and absorption,and thus present as better alternatives to inorganic Zinc salts.The main aim of this review was to assess the potential use of Zinc chelating peptides based on their ability to enhance Zinc absorption.Advances in research of Zinc absorption and metabolism were stated,and the structure-function relationship of Zinc chelating peptides was also discussed.According to the preferred reporting items for systematic reviews and meta-analyses(PRISMA)reporting guidelines,all relevant articles published from inception to march2021 were identified and extracted from Pub Med,CABI,and Science direct.The keywords which we used to collect and screen the articles were “Zinc chelating peptides”,“Zinc binding peptides”,“Zinc peptides”,“protein hydrolysate Zinc”,“Peptide Zinc complex”,“Zinc peptide absorption”and so on.A total of 29 studies reported in 27 articles were identified.Currently,detailed mechanisms including which transporter plays what role in cellular distribution of Zinc in enterocytes and transfer across the cells after being absorbed is still not well understood.However,to date,twenty-four known membrane transporters(10 Zn T and 14 ZIP)are believed to be involved in Zinc homeostasis regulation,and functions,as well as their response to Zinc status,or availability of some of these Zinc transporters have been deduced;ZIP-4,and Zn T-5B are apically localized.ZIP-4 imports Zinc from the lumen into the enterocytes and is upregulated in low levels of Zinc and vice versa,while Zn T-5B functions bidirectionally.Zn T-1,ZIP-5 and ZIP-14 are localized on the basolateral surface;Zn T-1 transports Zinc on the basolateral side of the enterocytes into the portal blood,and its expression is down-regulated when Zinc intake is increased,while Zn T-5 and ZIP-14 import Zinc from blood circulation into the enterocytes,possibly serving to communicate serum Zinc levels to the enterocytes so as to control the level of Zinc absorption from the diet.Zn T-2 to Zn T-7 are highly expressed in intracellular structures in enterocytes and are presumed to function to facilitate Zinc influx in intracellular structures such as vesicles,endosomes and Golgi complex.Metallothionein also play a role in Zinc absorption,they regulate free levels of Zinc by binding Zinc ions that are absorbed into the cells and transfer them to Zinc transporters.Of the 29 studies,11 were used to analyse the structure-function relationship of Zinc chelating peptides.The peptides reported from these studies ranged between 236 and1882.08 Daltons.Peptides with the lowest molecular weight did not exhibit the highest Zinc chelating capacity and vice versa,indicating that molecular weight is not the major determinant of Zinc chelating capacity.On the other hand,peptides with lower net charge(more negative or closer to a negative charge)exhibited the highest Zinc chelating peptides among peptides produced from the same source,indicating that net charge may play a relatively more important role,this high Zinc chelating capacity may be due to the abundance of negative charges that provide more sites for Zinc to bind.However,the fact that a Soy peptide(KYKRQRW)exhibited a high Zinc chelating capacity(82%)despite having a high net charge of 4,indicates that the influence of net charge in Zinc chelation might be limited,and that amino acid composition and sequence plays a dominant role.The presence of certain amino acids such as histidine(His),cysteine(Cys),glutamic(Glu),Asparagine(Asn),glutamine(Gln),Serine(Ser)A,spartic(Asp),lysine(Lys),arginine(Arg),and Methionine(Met)have been reported to serve as ligands to bind Zinc.Several Zinc chelating peptides composed of the aforementioned amino acids have been produced,however,some exhibit stronger Zinc chelating capacities than others,it is hypothesized that the varying Zinc chelation capacities may be due to the abundance of chelators,presence of strong chelators in some peptides,or the position of certain amino acids at the N-terminal.For instance,peptides with abundance in chelators exhibited higher Zinc chelating capacities.Contrastingly,peptides with fewer chelators but composed of strong chelators such as Ser and Met had higher Zinc chelating capacity.These studies suggest that,the Zinc chelating capacity of peptides increases according to Position of chelator > chelator strength > abundance of chelators > net charge > molecular weight.The effect of Zinc chelating peptides on Zinc absorption was determined in vitro using Caco-2 cells,Zinc retention and transport were measured based on the Zinc content on the cell apical and basolateral compartment respectively,and the Zinc absorption was evaluated based on Zinc retention and transport.In the 7 selected studies,4 showed Zinc chelating peptides could enhanced Zinc absorption,in 1 study,Zinc chelating peptides also enhanced Zinc retention,in 3 studies,Zinc chelating peptides enhanced Zinc transport.,in one study,Zinc chelating peptides were able to enhance Zinc transport and uptake more than Zn SO4(by 23.26%),in 1 study the Zinc retention and absorption were reduced.,and in 1 study,Zinc chelating peptides had an insignificant effect on Zinc retention,transport and absorption.The enhanced Zinc retention,transportation and absorption was attributed to the strong binding of Zinc to peptides which in result prevents precipitation and interactions with other intestinal components,and facilitates their absorption through peptide transport mechanisms.The insignificant/no effect in enhancing Zinc retention,transport and absorption may be due to the presence of Zinc absorption inhibitors present in the matrix.5 studies were used to analyse the effects of Zinc chelating peptides on Zinc absorption in vivo;in 3 studies,Zinc chelating peptides enhanced Zinc absorption while in 2 studies,Zinc chelating peptides had an insignificant to no effect on Zinc absorption.The positive effects are due to the formation of soluble complexes between Zinc and peptides,which prevent competitive inhibition by other nutrients such as iron,and insoluble complex formation of Zinc and antinutrients such as phytate.The insignificant or no effect on Zinc absorption may be due to numerous factors such as the form administered,concentration of the bioactive peptides,biomarker used,and quantity of Zinc absorption inhibitors(such as phytate and iron).1 study was used to analyse the effect of protein hydrolysate on Zinc absorption ex vivo.The protein hydrolysates were able to enhance Zinc transport and absorption.The protein hydrolysate was able to enhanced Zinc transport and absorption by preventing the co-precipitation of Zinc by mediating Zinc/Calcium Phosphate nano complex formation.According to the intestinal transport mechanism,it was deduced that the absorption of Zinc from Zinc/Calcium Phosphate nano complexes involved macro-pinocytic internalization,lysosomal degradation,and transcytosis.5 studies were used to compare Zinc bioavailability between protein hydrolysates/peptide and inorganic Zinc salts.Among the 5 studies,4 investigated their solubility and dialyzability,and 1 study investigated their stability.The Zinc solubility and stability in both hydrolysate-Zinc complexes(including peptide-Zinc complex),and inorganic Zinc salts were negatively affected by changes in the p H;the Zinc solubilizing percentages were significantly higher in acidic conditions of the stomach than alkaline conditions of the intestinal environment.However,in both gastric and intestinal conditions,hydrolysate-Zinc complex(including peptide-Zinc complex),had a higher solubility than inorganic Zinc salts.The high Zinc-solubilizing ability of protein hydrolysates make them more dialyzable,thus,the dialyzability percentages of hydrolysate-Zinc complexes were significantly higher than that of Zinc salts.Similarly,in both gastric and intestinal conditions,the stability of hydrolysate-Zinc complex was significantly higher than inorganic Zinc salt,probably due to strong binding forces that prevent them from easily dissociating.Overall,this indicates that protein hydrolysateZinc complexes(including peptide-Zinc complex)are more bioavailable than inorganic Zinc salts.The systematic review showed that bioactive peptides are able to chelate Zinc and enhance its absorption,and thus,could be used as alternatives to Zinc salts in functional foods and supplements. |
