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Biomolecules Aug 2020α-Lactalbumin (α-LA) is a small (Mr 14,200), acidic (pI 4-5), Ca-binding protein. α-LA is a regulatory component of lactose synthase enzyme system functioning in the... (Review)
Review
α-Lactalbumin (α-LA) is a small (Mr 14,200), acidic (pI 4-5), Ca-binding protein. α-LA is a regulatory component of lactose synthase enzyme system functioning in the lactating mammary gland. The protein possesses a single strong Ca-binding site, which can also bind Mg, Mn, Na, K, and some other metal cations. It contains several distinct Zn-binding sites. Physical properties of α-LA strongly depend on the occupation of its metal binding sites by metal ions. In the absence of bound metal ions, α-LA is in the molten globule-like state. The binding of metal ions, and especially of Ca, increases stability of α-LA against the action of heat, various denaturing agents and proteases, while the binding of Zn to the Ca-loaded protein decreases its stability and causes its aggregation. At pH 2, the protein is in the classical molten globule state. α-LA can associate with membranes at neutral or slightly acidic pH at physiological temperatures. Depending on external conditions, α-LA can form amyloid fibrils, amorphous aggregates, nanoparticles, and nanotubes. Some of these aggregated states of α-LA can be used in practical applications such as drug delivery to tissues and organs. α-LA and some of its fragments possess bactericidal and antiviral activities. Complexes of partially unfolded α-LA with oleic acid are cytotoxic to various tumor and bacterial cells. α-LA in the cytotoxic complexes plays a role of a delivery carrier of cytotoxic fatty acid molecules into tumor and bacterial cells across the cell membrane. Perhaps in the future the complexes of α-LA with oleic acid will be used for development of new anti-cancer drugs.
Topics: Animals; Antineoplastic Agents; Humans; Hydrogen-Ion Concentration; Lactalbumin; Neoplasms; Oleic Acid
PubMed: 32825311
DOI: 10.3390/biom10091210 -
Nutrition Reviews Jun 2018α-Lactalbumin is a whey protein that constitutes approximately 22% of the proteins in human milk and approximately 3.5% of those in bovine milk. Within the mammary... (Review)
Review
α-Lactalbumin is a whey protein that constitutes approximately 22% of the proteins in human milk and approximately 3.5% of those in bovine milk. Within the mammary gland, α-lactalbumin plays a central role in milk production as part of the lactose synthase complex required for lactose formation, which drives milk volume. It is an important source of bioactive peptides and essential amino acids, including tryptophan, lysine, branched-chain amino acids, and sulfur-containing amino acids, all of which are crucial for infant nutrition. α-Lactalbumin contributes to infant development, and the commercial availability of α-lactalbumin allows infant formulas to be reformulated to have a reduced protein content. Likewise, because of its physical characteristics, which include water solubility and heat stability, α-lactalbumin has the potential to be added to food products as a supplemental protein. It also has potential as a nutritional supplement to support neurological function and sleep in adults, owing to its unique tryptophan content. Other components of α-lactalbumin that may have usefulness in nutritional supplements include the branched-chain amino acid leucine, which promotes protein accretion in skeletal muscle, and bioactive peptides, which possess prebiotic and antibacterial properties. This review describes the characteristics of α-lactalbumin and examines the potential applications of α-lactalbumin for human health.
Topics: Adult; Amino Acids; Amino Acids, Essential; Animals; Cattle; Child Development; Dietary Supplements; Female; Humans; Infant; Infant Formula; Infant Nutritional Physiological Phenomena; Lactalbumin; Male; Milk, Human; Nutritional Status
PubMed: 29617841
DOI: 10.1093/nutrit/nuy004 -
FEBS Letters May 2000Small milk protein alpha-lactalbumin (alpha-LA), a component of lactose synthase, is a simple model Ca(2+) binding protein, which does not belong to the EF-hand... (Review)
Review
Small milk protein alpha-lactalbumin (alpha-LA), a component of lactose synthase, is a simple model Ca(2+) binding protein, which does not belong to the EF-hand proteins, and a classical example of molten globule state. It has a strong Ca(2+) binding site, which binds Mg(2+), Mn(2+), Na(+), and K(+), and several distinct Zn(2+) binding sites. The binding of cations to the Ca(2+) site increases protein stability against action of heat and various denaturing agents, while the binding of Zn(2+) to the Ca(2+)-loaded protein decreases its stability. Functioning of alpha-LA requires its interactions with membranes, proteins, peptides and low molecular weight substrates and products. It was shown that these interactions are modulated by the binding of metal cations. Recently it was found that some folding variants of alpha-LA demonstrate bactericidal activity and some of them cause apoptosis of tumor cells.
Topics: Amino Acid Sequence; Calcium; Cations; Cell Membrane; Lactalbumin; Protein Binding; Protein Structure, Secondary; Protein Structure, Tertiary
PubMed: 10818224
DOI: 10.1016/s0014-5793(00)01546-5 -
Journal of Biological Inorganic... Oct 2022There is limited knowledge regarding α-lactalbumin amyloid aggregation and its mechanism. We examined the formation of α-lactalbumin amyloid fibrils (α-LAF) in the...
There is limited knowledge regarding α-lactalbumin amyloid aggregation and its mechanism. We examined the formation of α-lactalbumin amyloid fibrils (α-LAF) in the presence of cations (Mg<sup>2+</sup>, Ca<sup>2+</sup>, Na<sup>+</sup>, K<sup>+</sup>, NH<sub>4</sub><sup>+</sup>, and Cs<sup>+</sup>) in the form of chloride salts at two concentrations. We have shown that studied cations affect the conformation of α-lactalbumin, the kinetics of its amyloid formation, morphology, and secondary structure of α-LAF in a different manner. The higher salts concentration significantly accelerated the aggregation process. Both salt concentrations stabilized α-lactalbumin's secondary structure. However, the presence of divalent cations resulted in shorter fibrils with less β-sheet content. Moreover, strongly hydrated Mg<sup>2+</sup> significantly altered α-lactalbumin's tertiary structure, followed by Na<sup>+</sup>, NH<sub>4</sub><sup>+</sup>, K<sup>+</sup>, and weakly hydrated Cs<sup>+</sup>. On the other hand, Ca<sup>2+</sup>, despite being also strongly hydrated, stabilized the tertiary structure, supposedly due to its high affinity towards α-lactalbumin. Yet, Ca<sup>2+</sup> was not able to inhibit α-lactalbumin amyloid aggregation.
Topics: Amyloid; Amyloidogenic Proteins; Amyloidosis; Cations; Cations, Divalent; Chlorides; Humans; Lactalbumin; Salts
PubMed: 36151481
DOI: 10.1007/s00775-022-01962-3 -
Nihon Rinsho. Japanese Journal of... Aug 1999
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Critical Reviews in Food Science and... Sep 2011α-Lactalbumin (α-LA) is a whey protein that has been extensively studied for its folding properties and its ability to bind several cations. An interesting property of... (Review)
Review
α-Lactalbumin (α-LA) is a whey protein that has been extensively studied for its folding properties and its ability to bind several cations. An interesting property of α-LA is its ability to interact with fatty acids, although this interaction requires the previous unfolding of the protein by removing the Ca(2+) bound. The main function of α-LA is to participate in lactose biosynthesis. However, other biological functions have been attributed to the protein in the last decade. It has been reported that a particular form of human and bovine apo-α-LA induces apoptosis in tumoral and immature cells though spares healthy differentiated cells. The conversion of α-LA to the active apoptotic form requires the unfolding of the protein and the binding of specific fatty acids, mainly unsaturated C18 fatty acids in the cis-conformation. Likewise, it has been shown that a folding variant of α-LA and also some peptidic fragments have a bactericidal activity. The proposed functions for α-LA open new perspectives for its use as a potential ingredient to be added in functional foods or in nutraceutical products. This review summarizes the current state of knowledge on the subject of the interaction of α-LA with fatty acids, and the consequences of this interaction on its bioactivity.
Topics: Animals; Anti-Bacterial Agents; Antineoplastic Agents; Apoptosis; Cattle; Fatty Acids; Lactalbumin; Milk
PubMed: 21838558
DOI: 10.1080/10408398.2010.481368 -
Journal of Agricultural and Food... Mar 2022Alpha-lactalbumin (α-LA; the most abundant whey protein in human milk) contributes to infant development, providing bioactive peptides and essential amino acids. Here,...
Alpha-lactalbumin (α-LA; the most abundant whey protein in human milk) contributes to infant development, providing bioactive peptides and essential amino acids. Here, () was selected as the production host. We found that the host X33 was suitable for expressing the target protein, yielding 5.2 mg·L α-LA. Thereafter, several secretory signal peptides were applied to obtain a higher titer of α-LA. The strain with α-factor secretory signal peptide secreted the highest extracellular titer. Additionally, promoters , , and were compared and applied. The strain with the promoter produced the highest extracellular titer. In addition, coexpressing human protein disulfide isomerase A3 (h) increased the titer by 27%. Human α-LA production by the strain X33-pPICZαA-hLALBA-hPDIA3 reached 56.3 mg·L in a 3 L bioreactor. This is the first report of successful secretory human α-LA expression in and lays foundations for the simulation of human milk for infant formulas and further development of bioengineered milk.
Topics: Child; Humans; Lactalbumin; Milk, Human; Pichia; Saccharomycetales
PubMed: 35148078
DOI: 10.1021/acs.jafc.1c07908 -
The Journal of Nutrition Mar 1991The ideal "humanization" of milk substitutes should include the creation of an amino acid pattern closely resembling that of human milk. Because the mixture of proteins... (Review)
Review
The ideal "humanization" of milk substitutes should include the creation of an amino acid pattern closely resembling that of human milk. Because the mixture of proteins in human milk is particularly rich in tryptophan and cysteine and low in methionine, this pattern is difficult to achieve with commercially available proteins. Even whey-predominant formulas only approximate human milk. Human milk has a high concentration of whey protein (70% of total protein). Of this, alpha-lactalbumin, a component of the lactase synthetase complex, accounts for 41% of the whey and 28% of the total protein. Only 3% of the protein in bovine milk is alpha-lactalbumin. Human and bovine alpha-lactalbumin share a 72% amino acid sequence homology. Both proteins contain (wt/wt) 6% tryptophan and 5% cysteine but only 0.9% methionine. Thus the differences in the amino acid compositions of bovine and human milks are largely attributable to differences in their alpha-lactalbumin contents. Commercial availability of bovine alpha-lactalbumin would allow the construction of infant formulas with amino acid compositions that are very close to that of human milk. alpha-Lactalbumin would also be a valuable constituent of diets for patients whose protein intake must be restricted.
Topics: Amino Acids; Biological Availability; Digestion; Humans; Infant Food; Infant Nutritional Physiological Phenomena; Infant, Newborn; Lactalbumin; Milk Proteins; Milk, Human
PubMed: 2002399
DOI: 10.1093/jn/121.3.277 -
Current Protein & Peptide Science 2016This is a concluding part of the three-part article from a series of reviews on the abundance and roles of intrinsic disorder in milk proteins. In this paper, we... (Review)
Review
This is a concluding part of the three-part article from a series of reviews on the abundance and roles of intrinsic disorder in milk proteins. In this paper, we describe the peculiarities of metal binding to a multifunctional milk protein, α-lactalbumin, which has two domains, a large α-helical domain and a small β-sheet domain connected by a calcium binding loop. It is known that in addition to four disulfide bonds, the native fold of this protein is stabilized by binding of a calcium ion. In fact, although in various mammals, α-lactalbumins are rather poorly conserved possessing the overall sequence identity of ~16%, the positions of all eight cysteines and a calcium binding site (residues DKFLDDDITDDI in human protein) are strongly conserved. Curiously, this conserved calcium binding loop is located within a region with increased structural flexibility. Besides canonical calcium binding, α-lactalbumin is known to interact with other metals, such as zinc (for which it has a specific binding site), and, in its apo-form, it can bind other divalent and monovalent cations. The binding of Mg2+, Na+, and K+ to the Ca2+ site increases α-lactalbumin stability against action of heat and various denaturing agents, with the higher stabilization effects being imposed by the stronger bound metal ions.
Topics: Animals; Binding Sites; Calcium; Humans; Lactalbumin; Metals; Models, Molecular; Protein Binding; Protein Conformation; Thermodynamics
PubMed: 27238572
DOI: 10.2174/1389203717666160530151534 -
International Immunopharmacology Dec 2022Cardiovascular aging is the most important factor leading to cardiovascular disease (CVD), and the incidence and severity of cardiovascular events increase with age....
Cardiovascular aging is the most important factor leading to cardiovascular disease (CVD), and the incidence and severity of cardiovascular events increase with age. Cardiovascular disease is one of the leading causes of death in the aging population. Therefore, it is extremely urgent to develop and explore effective drugs or bioactive molecules to prevent cardiovascular aging and related diseases. In the current work, the effect of bovine α-lactalbumin (α-lactalbumin is one of the major bioactive protein molecules in milk) on cardiovascular aging was investigated in vitro and in vivo. First, a cellular model of cardiovascular aging was established using HO-induced in vitro cellular models. It was found that α-lactalbumin could alleviate cardiovascular senescence by assessing Sa-β-gal and senescence-related markers (such as p16/p21/p53) in in vitro cellular models. Bovine α-lactalbumin attenuated aging-related inflammation and oxidative stress. Furthermore, aged mice were used as an in vivo cardiovascular aging model. We explored the effect of α-lactalbumin on cardiovascular aging and found that cardiovascular aging was significantly attenuated by evaluating Sa-β-gal staining and aging-related marker molecules. Mechanistically, we found that α-lactalbumin may alleviate cardiovascular aging by regulating the expression of Sirt1 (Sirtuin 1). In summary, in the current work, we systematically explored the potential biological activity of α-lactalbumin against cardiovascular aging and found that α-lactalbumin has good anti-aging potential in vitro and in vivo, suggesting that α-lactalbumin could be used as an antiaging functional food in the future.
Topics: Mice; Cattle; Animals; Lactalbumin; Cellular Senescence; Hydrogen Peroxide; Cardiovascular Diseases; Aging; Sirtuin 1
PubMed: 36252495
DOI: 10.1016/j.intimp.2022.109291