Egg White, Eggs, Glycoprotein, Iron
by
0

Ovotransferrin aka conalbumin

Ovotransferrin (conalbumin) is a glycoprotein of egg white albumen. Egg white albumen is composed of multiple proteins, of which ovotransferrin is the most heat reliable. It has a molecular weight of 76,000 daltons and contains about 700 amino acids. Ovotransferrin makes up approximately 13% of egg albumen (in contrast to ovalbumin, which comprises 54%). As a member of the transferrin and metalloproteinase family, ovotransferrin has been found to possess antibacterial and antioxydant and immunomodulatory properties, arising primarily through its iron (Fe3+) binding capacity by locking away a key biochemical component necessary for micro-organismal survival. Bacteria starved of iron are rendered incapable of moving, making ovotransferrin a potent bacteriostatic.

  • “OVOTRANSFERRIN: The nutraceutical protein with antimicrobial, antioxidant and immunomodulatory properties”. Bioseutica B.V.
  • Wu J, Acero-Lopez A (2012). “Ovotransferrin: Structure, bioactivities, and preparation”. Food Research International. 46 (2): 480–487. doi:10.1016/j.foodres.2011.07.012 Ovotransferrin, accounting for about 12–13% of total egg white proteins, is synthesized by the avian transferrin gene in the oviduct. It is made of a monomeric glycoprotein consisting of 686 amino acid residues. As a member of transferrin family, ovotransferrin folds into two globular lobes, each containing an iron-binding site located within the interdomain cleft of each lobe. In addition to providing antimicrobial activity, it also functions to transport iron to the developing embryo. The antimicrobial property of ovotransferrin is thought to be due to its ability to sequester the iron necessary for the growth of microorganisms, rendering then iron deprived. Recent evidence further suggests that its role as an essential component of the egg’s antimicrobial defense system is very likely iron independent. This antimicrobial property implies its applications as an infant formula ingredient, a food additive, and an antimicrobial agent for improving animal health. A wide range of bioactivities such as antifungal, antiviral, anticancer, antioxidative, antihypertensive, and immunomodulatory activities have been reported recently for ovotransferrin or its derived peptides. In this review, the structure, bioactivity, and preparation of ovotransferrin are presented, and its potential as a nutraceutical and functional food ingredient is described.

Structure

Ovotransferrin is folded in a way that forms two lobes (N- and C- terminals) and each lobe consists of a binding site. Each lobe is then divided into two domains of 160 amino acid residues. Its structure also consists of fifteen disulfide crosslinks and no free sulfhydryl groups. Disulfide groups stabilize the tertiary structures of proteins. Transferrins are iron binding proteins and acute phase reactants of animal serum. It has a binding log of 15 at a pH of 7 or above, meaning that the iron binding capacity of ovotransferrin rapidly decreased at a pH that is less than 6. This family is also known for their role in cell maturation by transporting essential nutrients to developing embryos. Ovotransferrin functions as an antimicrobial agent and transports iron to the developing embryo. Because they bind to iron, this makes it difficult for harmful bacteria to be nutritionally satisfied with them so it acts as an antimicrobial.

The primary sequence of ovotransferrin is similar to that of many serum transferrins found in other species. Recently, scientists have discovered a blood serum transferrin in humans, that binds iron like ovotransferrin and which shows 50% homology to ovotransferrin, i.e., they have similar amino acid composition and carbohydrate content. At the C- lobe, human serum has two N-glycans while the hen ovotransferrin has a single N-glycan. Consequently, structurally this protein differs from its serum counterpart because of its glycosylation pattern. These proteins are said to be glycosylated because they have carbohydrates attached to them. Glycosylation is the most common covalent modification (formation of chemical bonds) that occurs in living organisms. This process is determined by the structure of the protein backbone and the carbohydrate attachment site.

In addition, ovotransferrin is glycosylated by the N-linkage to the amino acid known as asparagine, meaning that the glycan, the carbohydrate chain, is attached to the nitrogen on the amino acid. Asparagine, found abundantly in asparagus (hence, its name), is one of twenty of the most common amino acids and was the first amino acid to be isolated. While ovotransferrin identifies with its family, there are two types of ovotransferrin proteins: apo and holo. Apo-Ovotransferrin is deprived of iron and holo-Ovotransferrin is saturated with iron. Because the apo-ovotransferrin is iron-deprived, it is easily destroyed by physical and chemical treatments.

Function and mechanism

Biologically, conalbumin isolates and sequesters metallic contaminants in the egg white. Ovotransferrin is functionally and structurally analogous to mammalian lactoferrin A recent study has shown superior performance of ovotransferrin when compared to lactoferrin in its capability to deliver iron without accumulation or inducing gastric irritability, rendering ovotransferrin as an excellent potential iron carrier for the treatment of Iron-deficiency anemia (IDA). Ovotransferrin showed superior physiological iron delivery over lactoferrin in a gastric barrier model. This data holds much promise for ovotransferrin’s use in food supplements, with dual functionality as both antimicrobial and iron delivery mechanism.

  • “Conalbumin”. steadyhealth. Archived from the original on 2011-07-16.
  • Giansanti F, Leboffe L, Angelucci F, Antonini G (November 2015). “The Nutraceutical Properties of Ovotransferrin and Its Potential Utilization as a Functional Food”. Nutrients. 7 (11): 9105–9115. doi:10.3390/nu7115453. PMC 4663581. PMID 26556366. Ovotransferrin or conalbumin belong to the transferrin protein family and is endowed with both iron-transfer and protective activities. In addition to its well-known antibacterial properties, ovotransferrin displays other protective roles similar to those already ascertained for the homologous mammalian lactoferrin. These additional functions, in many cases not directly related to iron binding, are also displayed by the peptides derived from partial hydrolysis of ovotransferrin, suggesting a direct relationship between egg consumption and human health.
  • Galla R, Grisenti P, Farghali M, Saccuman L, Ferraboschi P, Uberti F (October 2021). “Ovotransferrin Supplementation Improves the Iron Absorption: An In Vitro Gastro-Intestinal Model”. Biomedicines. 9 (11): 1543. doi:10.3390/biomedicines9111543. PMC 8615417. PMID 34829772. Transferrins constitute the most important iron regulation system in vertebrates and some invertebrates. Soluble transferrins, such as bovine lactoferrin and hen egg white ovotransferrin, are glycoproteins with a very similar structure with lobes that complex with iron. In this in vitro study, a comparison of bovine lactoferrin and ovotransferrin was undertaken to confirm the comparability of biological effects. An in vitro gastric barrier model using gastric epithelial cells GTL-16 and an in vitro intestinal barrier model using CaCo-2 cells was employed to evaluate iron absorption and barrier integrity. An analysis of the molecular pathways involving DMT-1 (divalent metal transporter 1), ferritin and ferroportin was also carried out. These in vitro data demonstrate the activity of both 15% saturated and 100% saturated ovotransferrin on the iron regulation system. Compared with the commercial bovine lactoferrin, both 15% saturated and 100% saturated ovotransferrin were found to act in a more physiological manner. Based on these data, it is possible to hypothesise that ovotransferrin may be an excellent candidate for iron supplementation in humans; in particular, 15% saturated ovotransferrin is the overall best performing product. In vivo studies should be performed to confirm this in vitro data.

Role in disease and therapy

Numerous studies have identified dual anti-osteoporotic properties of ovotransferrin, both reducing bone resorption and promoting bone formation. Beyond this, ovotransferrin shows promise as a drug carrier with potential applications in cancer treatment. Indeed, ovotransferrin alone is toxic to cancer cells in-vitro. Its antioxidant and anti-inflammatory properties may also make ovotransferrin a viable treatment for cardiovascular disease.

  • Shang N, Wu J (March 2018). “Egg White Ovotransferrin Shows Osteogenic Activity in Osteoblast Cells”. Journal of Agricultural and Food Chemistry. 66 (11): 2775–2782. doi:10.1021/acs.jafc.8b00069. PMID 29502401. Ovotransferrin, the major protein in egg white, is a member of transferrin family. The objective of this study was to study the effects of ovotransferrin on cell proliferation, differentiation, mineralization and osteoclastogenesis of bone osteoblast cells. Effect of ovotransferrin (concentrations ranging from 1 to 1000 μg/mL) on the proliferation, differentiation, and mineralization of mouse osteoblast cells MC3T3-E1 was determined by 5-bromo-2-deoxyuridine (BrdU) incorporation assay, Western blot, immunofluorescence, and Alizarin-S red staining, respectively. Our results showed that ovotransferrin stimulated cell proliferation (enhanced BrdU incorporation), differentiation (enhanced expression of alkaline phosphatase and type-I collagen), and mineralization (increased calcium deposits) in a dose-dependent manner. Furthermore, ovotransferrin could increase the expression of osteoprotegerin (OPG) while decreasing the expression of receptor activator of nuclear factor kappa-B ligand (RANKL), suggesting its role in inhibition of bone resorption. This study demonstrated for the first time that ovotransferrin might promote bone formation while preventing bone resorption, which might open up a new application of egg white protein ovotransferrin as a functional ingredient in bone health management.
  • Ibrahim HR, Kiyono T (December 2009). “Novel anticancer activity of the autocleaved ovotransferrin against human colon and breast cancer cells”. Journal of Agricultural and Food Chemistry. 57 (23): 11383–11390. doi:10.1021/jf902638e. PMID 19886663. Proteins of avian egg albumin have been suggested to play various biological roles during the development of chick embryo to confer protection. Recently, we have shown that ovotransferrin (OTf), the second major protein in egg albumin, undergoes thiol-linked autocleavage at distinct sites upon reduction. This study explores the physiological significance of OTf autocleavage by examining the effect of the reduced autocleaved OTf (termed rac-OTf) on modulation of cell proliferation, lethality, and apoptosis in two human cancer cell lines, colon cancer (HCT-116) and breast cancer (MCF-7). The rac-OTf was prepared by reduction of OTf with a non-thiol reductant (TCEP), to avoid reductive alkylation and produce highly soluble fragments. Unlike OTf, rac-OTf remarkably inhibited the proliferation of cancerous MCF-7 and HCT-116 cells in a dose-dependent manner, with the greatest effect on HCT-116, but had no effect on normal human mammary epithelial cells (HMEC). Cytofluorometric and trypan blue exclusion analyses indicated that rac-OTf exhibits cytotoxicity to HCT-116 in a dose-dependent fashion. The cytotoxic mechanism of rac-OTf against cancer cells was found to be induction of apoptosis as judged by changes in cell morphology, annexin-V binding, collapse of mitochondrial membrane potential, and caspase-9 and -6 activation, indicating the involvement of the mitochondrial pathway. This finding is the first to describe the reduction-dependent autocleaved OTf as an anticancer molecule, providing insights into a novel physiological function of OTf, suggesting its therapeutic potential in the treatment of human cancers and health benefit in nutraceuticals.
  • Lee N, Cheng J, Enomoto T, Nakano YO (December 2009). “One peptide derived from hen ovotransferrin as pro-drug to inhibit angiotensin converting enzyme”. Journal of Food and Drug Analysis. 57 (23): 11383–11390. doi:10.38212/2224-6614.2505. Angiotensin I-converting enzyme (ACE) inhibitory peptide was derived from hen ovotransferrin and identified as Lys-Val-Arg-Glu-Gly-Thr-Thr-Tyr. It produced a concentration-dependent inhibition of ACE activity in vitro with an IC50 value of 102.8 μM. After hydrolysis by ACE, the product (Lys-Val-Arg-Glu-Gly-Thr) has an IC50 value of 9.1 μM that was about 11-fold lower of the parent peptide. Thus, Lys-Val-Arg-Glu-Gly-Thr-Thr-Tyr can be considered as a pro-drug. Moreover, Lys-Val-Arg-Glu-Gly-Thr-Thr-Tyr and Lys-Val-Arg-Glu-Gly-Thr were intravenously administered into spontaneously hypertensive rats (SHR) to monitor the time-course change of systolic blood pressure. We found that Lys-Val-Arg-Glu-Gly-Thr-Thr-Tyr and its hydrolyzed product produced the maximal reduction of systolic blood pressure at 40 min and 20 min after injection, respectively. This 20 min delay might be considered as the time required for conversion of prodrug into Lys-Val-Arg-Glu-Gly-Thr, the true ACE inhibitor. In conclusion, the obtained results suggest that Lys-Val-Arg-Glu-Gly-Thr-Thr-Tyr works as the pro-drug of Lys-Val-Arg-Glu-Gly-Thr to inhibit ACE activity in vivo.
  • Chen S, Jiang H, Peng H, Wu X, Fang J (2018). “The Utility of Ovotransferrin and Ovotransferrin-Derived Peptides as Possible Candidates in the Clinical Treatment of Cardiovascular Diseases”. Oxidative Medicine and Cellular Longevity. 2017: 6504518. doi:10.1155/2017/6504518. PMC 5366766. PMID 28386310. Several of the most prevalent etiological factors which contribute towards global death rates are associated with cardiovascular diseases (CVDs), which include a range of conditions such as angina, rheumatic heart disease, and venous thrombosis. Extensive research has been conducted into the role played by oxidative stress and inflammation in the functional transformations associated with the progression of CVDs, while the research findings from these investigations have been both fruitful and informative. In view of the adverse secondary effects that result from the clinical administration of many synthetic medications, research which explored the treatment of severe and long-lasting conditions, including CVDs, has primarily centered on the potential benefits displayed by natural agents, one of which is food protein-based bioactive peptides. Most importantly, previous research has revealed the possible benefits associated with these products’ anti-inflammatory and antioxidant characteristics. In light of these considerations, this paper aims to review the degree to which ovotransferrin (otrf, also referred to as conalbumin) and otrf-derived peptides, including IRW, IQW, and KVREGT, are, by virtue of their anti-inflammatory and antioxidant characteristics, viable treatment agents for endothelial dysfunction and the prevention of CVD.

See also

References

  1. “OVOTRANSFERRIN: The nutraceutical protein with antimicrobial, antioxidant and immunomodulatory properties”. Bioseutica B.V.
  2. Wu J, Acero-Lopez A (2012). “Ovotransferrin: Structure, bioactivities, and preparation”. Food Research International. 46 (2): 480–487. doi:10.1016/j.foodres.2011.07.012.
  3. “Conalbumin”. steadyhealth. Archived from the original on 2011-07-16.
  4. Giansanti F, Leboffe L, Angelucci F, Antonini G (November 2015). “The Nutraceutical Properties of Ovotransferrin and Its Potential Utilization as a Functional Food”. Nutrients. 7 (11): 9105–9115. doi:10.3390/nu7115453. PMC 4663581. PMID 26556366.
  5. Galla R, Grisenti P, Farghali M, Saccuman L, Ferraboschi P, Uberti F (October 2021). “Ovotransferrin Supplementation Improves the Iron Absorption: An In Vitro Gastro-Intestinal Model”. Biomedicines. 9 (11): 1543. doi:10.3390/biomedicines9111543. PMC 8615417. PMID 34829772.
  6. Shang N, Wu J (March 2018). “Egg White Ovotransferrin Shows Osteogenic Activity in Osteoblast Cells”. Journal of Agricultural and Food Chemistry. 66 (11): 2775–2782. doi:10.1021/acs.jafc.8b00069. PMID 29502401.
  7. Ibrahim HR, Kiyono T (December 2009). “Novel anticancer activity of the autocleaved ovotransferrin against human colon and breast cancer cells”. Journal of Agricultural and Food Chemistry. 57 (23): 11383–11390. doi:10.1021/jf902638e. PMID 19886663.
  8. Lee N, Cheng J, Enomoto T, Nakano YO (December 2009). “One peptide derived from hen ovotransferrin as pro-drug to inhibit angiotensin converting enzyme”. Journal of Food and Drug Analysis. 57 (23): 11383–11390. doi:10.38212/2224-6614.2505.
  9. Chen S, Jiang H, Peng H, Wu X, Fang J (2018). “The Utility of Ovotransferrin and Ovotransferrin-Derived Peptides as Possible Candidates in the Clinical Treatment of Cardiovascular Diseases”. Oxidative Medicine and Cellular Longevity. 2017: 6504518. doi:10.1155/2017/6504518. PMC 5366766. PMID 28386310.

External links

Globular proteins

Categories: 

/

Post a Comment

Your email address will not be published. Required fields are marked *