α-Lactalbumin is a protein present in the milk of almost all mammalian species. In primates, alpha-lactalbumin expression is upregulated in response to the hormone prolactin and increases the production of lactose.
α-Lactalbumin forms the regulatory subunit of the lactose synthase (LS) heterodimer and β-1,4-galactosyltransferase (beta4Gal-T1) forms the catalytic component. Together, these proteins enable LS to produce lactose by transferring galactose moieties to glucose. As a multimer, alpha-lactalbumin strongly binds calcium and zinc ions and may possess bactericidal or antitumor activity. A folding variant of human alpha-lactalbumin that may form in acidic environments such as the stomach, called HAMLET, probably induces apoptosis in tumor and immature cells.
Research by a Dr. Vincent Tuohy at the Cleveland Clinic is using α-Lactalbumin as the basis for a potential breast cancer vaccine. Breast cancer usually develops later in life, well after the typical child-bearing age. This protein is normally expressed only during late pregnancy and lactation, but Tuohy notes that expression is also common in newly formed tumours: “One of the things they do is make inappropriate proteins like α-lactalbumin". Dr. Tuohy's group has developed a vaccine that targets α-Lactalbumin, tricking the patient's own immune system to attack breast tissue that expresses the α-Lactalbumin genes and thus killing a high percentage of the cancerous cells. In fact, vaccinated mice achieved 100% protection against breast cancer, provided they were dosed before tumours began to develop. Tissue damage and inflammation were limited to the breast tissue of nursing animals. This should not be a problem for humans, as the highest risk breast cancer patients are generally past childbearing age.
The molecular weight is 14178 Da, and the isoelectric point is between 4.2 and 4.5. One of the main structural differences with beta-lactoglobulin is that it does not have any free thiol group that can serve as the starting-point for a covalent aggregation reaction. As a result, pure α-lactalbumin will not form gels upon denaturation and acidification.
The sequence comparison of α-lactalbumin shows a strong similarity to that of lysozymes, specifically the Ca2+-binding c-lysozyme. So the expected evolutionary history is that gene duplication of the c-lysozyme was followed by mutation. This gene predates the last common ancestor of mammals and birds, which probably puts its origin at about 300 Ma.
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