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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 -
Journal of Dairy Science Mar 2021α-Lactalbumin (α-LA) and β-lactoglobulin (β-LG) were isolated from yak milk and identified by mass spectrometry. The variant of α-LA (L8IIC8) in yak milk had 123...
α-Lactalbumin (α-LA) and β-lactoglobulin (β-LG) were isolated from yak milk and identified by mass spectrometry. The variant of α-LA (L8IIC8) in yak milk had 123 amino acids, and the sequence differed from α-LA from bovine milk. The amino acid at site 71 was Asn (N) in domestic yak milk, but Asp (D) in bovine and wild yak milk sequences. Yak β-LG had 2 variants, β-LG A (P02754) and β-LG E (L8J1Z0). Both domestic yak and wild yak milk contained β-LG E, but it was absent in bovine milk. The amino acid at site 158 of β-Lg E was Gly (G) in yak but Glu (E) in bovine. The yak α-LA and β-LG secondary structures were slightly different from those in bovine milk. The denaturation temperatures of yak α-LA and β-LG were 52.1°C and 80.9°C, respectively. This study provides insights relevant to food functionality, food safety control, and the biological properties of yak milk products.
Topics: Animals; Cattle; Lactalbumin; Lactoglobulins; Milk; Milk Proteins; Whey Proteins
PubMed: 33358811
DOI: 10.3168/jds.2020-18546 -
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 -
Nature Biomedical Engineering Jul 2020Theranostic agents should ideally be renally cleared and biodegradable. Here, we report the synthesis, characterization and theranostic applications of fluorescent...
Theranostic agents should ideally be renally cleared and biodegradable. Here, we report the synthesis, characterization and theranostic applications of fluorescent ultrasmall gold quantum clusters that are stabilized by the milk metalloprotein alpha-lactalbumin. We synthesized three types of these nanoprobes that together display fluorescence across the visible and near-infrared spectra when excited at a single wavelength through optical colour coding. In live tumour-bearing mice, the near-infrared nanoprobe generates contrast for fluorescence, X-ray computed tomography and magnetic resonance imaging, and exhibits long circulation times, low accumulation in the reticuloendothelial system, sustained tumour retention, insignificant toxicity and renal clearance. An intravenously administrated near-infrared nanoprobe with a large Stokes shift facilitated the detection and image-guided resection of breast tumours in vivo using a smartphone with modified optics. Moreover, the partially unfolded structure of alpha-lactalbumin in the nanoprobe helps with the formation of an anti-cancer lipoprotein complex with oleic acid that triggers the inhibition of the MAPK and PI3K-AKT pathways, immunogenic cell death and the recruitment of infiltrating macrophages. The biodegradability and safety profile of the nanoprobes make them suitable for the systemic detection and localized treatment of cancer.
Topics: Animals; Apoptosis; Breast Neoplasms; Cell Death; Female; Gold; Heterografts; Lactalbumin; Lipoproteins; Magnetic Resonance Imaging; Mice; Mice, Inbred BALB C; Mitogen-Activated Protein Kinase Kinases; Nanotechnology; Optical Imaging; Phosphatidylinositol 3-Kinases; Proteomics; Theranostic Nanomedicine
PubMed: 32661307
DOI: 10.1038/s41551-020-0584-z -
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 -
Nutrients Aug 2022To date, the involvement of α-Lactalbumin (α-LA) in the management of polycystic ovary syndrome (PCOS) refers to its ability to improve intestinal absorption of... (Review)
Review
To date, the involvement of α-Lactalbumin (α-LA) in the management of polycystic ovary syndrome (PCOS) refers to its ability to improve intestinal absorption of natural molecules like inositols, overcoming the inositol resistance. However, due to its own aminoacidic building blocks, α-LA is involved in various biological processes that can open new additional applications. A great portion of women with PCOS exhibit gastrointestinal dysbiosis, which is in turn one of the triggering mechanisms of the syndrome. Due to its prebiotic effect, α-LA can recover dysbiosis, also improving the insulin resistance, obesity and intestinal inflammation frequently associated with PCOS. Further observations suggest that altered gut microbiota negatively influence mental wellbeing. Depressive mood and low serotonin levels are indeed common features of women with PCOS. Thanks to its content of tryptophan, which is the precursor of serotonin, and considering the strict link between gut and brain, using α-LA contributes to preserving mental well-being by maintaining high levels of serotonin. In addition, considering women with PCOS seeking pregnancy, both altered microbiota and serotonin levels can induce later consequences in the offspring. Therefore, a deeper knowledge of potential applications of α-LA is required to transition to preclinical and clinical studies extending its therapeutic advantages in PCOS.
Topics: Dysbiosis; Female; Humans; Inositol; Insulin Resistance; Lactalbumin; Polycystic Ovary Syndrome; Pregnancy; Serotonin
PubMed: 35956395
DOI: 10.3390/nu14153220 -
Nutrition Reviews Dec 2021Milk proteins are known for their high nutritional quality, based on their essential amino acid composition, and they exhibit a wide range of bioactivities, including... (Review)
Review
Milk proteins are known for their high nutritional quality, based on their essential amino acid composition, and they exhibit a wide range of bioactivities, including satiety, antimicrobial, mineral-binding, and anti-lipidemic properties. Because of their unique water solubility, milk proteins are readily separated into casein and whey fractions, which can be further fractionated into many individual proteins, including alpha-S1- and alpha-S2-caseins, beta-casein, and kappa-casein, and the whey proteins alpha-lactalbumin, lactoferrin, beta-lactoglobulin, and glycomacropeptide. Many of these proteins have unique bioactivities. Further, over the past 30 years, peptides that are encrypted in the primary amino acid sequences of proteins and released along with amino acids during digestion are increasingly recognized as biologically active protein metabolites that may have beneficial effects on human health. This review examines the current state of the science on the contribution of dairy proteins and their unique peptides and amino acids to human health.
Topics: Amino Acids; Caseins; Humans; Lactalbumin; Milk Proteins; Peptides; Whey Proteins
PubMed: 34879145
DOI: 10.1093/nutrit/nuab097 -
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 -
Food Research International (Ottawa,... Feb 2023Calcium bioaccessibility depends on the amount of soluble calcium under intestinal digestion. The changes in calcium during in vitro static digestion of α-lactalbumin...
Calcium bioaccessibility depends on the amount of soluble calcium under intestinal digestion. The changes in calcium during in vitro static digestion of α-lactalbumin and β-lactoglobulin in presence of calcium chloride (0 mM, 20 mM and 50 mM) were followed by combining electrochemical determination of free calcium with the determination of soluble calcium by inductively coupled plasma optical emission spectroscopy. α-Lactalbumin and, more evident, β-lactoglobulin were found to increase calcium bioaccessibility with increasing intestinal digestion time by around 5% and 10%, respectively, due to the complex binding of calcium to peptides formed from protein hydrolysis by gastrointestinal enzymes. In vitro digested samples of β-lactoglobulin in presence of CaCl had nearly twice as much complex bound calcium as α-lactalbumin samples. The calcium bioaccessibility decreased significantly with the increasing concentration of added calcium chloride, although the amount of calcium chloride had little effect on the extension of digestion of α-lactalbumin and β-lactoglobulin. Simulated digestion fluids were found to have a negative effect on calcium bioaccessibility, especially the presence of hydrogen phosphate, and the amount of precipitated calcium increased significantly with increasing amount of added calcium chloride. Based on analysis and visualization by sequences of the peptides formed during digestion of α-lactalbumin and β-lactoglobulin, it was observed that peptides containing aspartic acid and glutamic acid acting as calcium chelators, may prevent precipitation of calcium in the intestines and increase calcium bioaccessibility. These results provide knowledge for the design of new dairy based functional foods to prevent calcium deficiency.
Topics: Lactalbumin; Lactoglobulins; Calcium; Calcium Chloride; Calcium, Dietary; Peptides; Digestion
PubMed: 36737996
DOI: 10.1016/j.foodres.2022.112415 -
Protein Science : a Publication of the... Sep 2021Amyloid fibrils are ordered aggregates that may be formed from disordered, partially unfolded, and fragments of proteins and peptides. There are several diseases, which...
Amyloid fibrils are ordered aggregates that may be formed from disordered, partially unfolded, and fragments of proteins and peptides. There are several diseases, which are due to the formation and deposition of insoluble β-sheet protein aggregates in various tissue, collectively known as amyloidosis. Here, we have used bovine α-lactalbumin as a model protein to understand the mechanism of amyloid fibril formation at pH 1.6 and 65°C under non-reducing conditions. Amyloid fibril formation is confirmed by Thioflavin T fluorescence and atomic force microscopy (AFM). Our finding demonstrates that hydrolysis of peptide bonds occurs under these conditions, which results in nicking and fragmentation. The nicking and fragmentation have been confirmed on non-reducing and reducing gel. We have identified the fragments by matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry. The fragmentation may initiate nucleation as it coincides with AFM images. Conformational changes associated with monomer resulting in fibrillation are shown by circular dichroism and Raman spectroscopy. The current study highlights the importance of nicking and fragmentation in amyloid fibril formation, which may help understand the role of acidic pH and proteolysis under in vivo conditions in the initiation of amyloid fibril formation.
Topics: Amino Acid Sequence; Amyloid; Amyloidogenic Proteins; Animals; Benzothiazoles; Cattle; Hot Temperature; Hydrogen-Ion Concentration; Lactalbumin; Microscopy, Atomic Force; Models, Chemical; Protein Conformation, alpha-Helical; Protein Conformation, beta-Strand; Proteolysis; Spectrometry, Fluorescence
PubMed: 34107116
DOI: 10.1002/pro.4144