Lactalbumin, alpha-, also known as LALBA, is a protein that in humans is encoded by the LALBA gene. Overview α-Lactalbumin is a protein that regulates the production of lactose 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. The corresponding folding dynamics of alpha-lactalbumin is thus highly unusual. When formed into a complex with Gal-T1, a galactosyltransferase, α-lactalbumin, enhances the enzyme's affinity for glucose by about 1000 times, and inhibits the ability to polymerise multiple galactose units. This gives rise to a pathway for forming lactose by converting Gal-TI to Lactose synthase. Physical properties The structure of alpha-lactalbumin is well known and is composed of 123 amino acids and 4 disulfide bridges. The molecular weight is 14178 Da, and the isoelectric point is between 4.2 and 4.5. Alpha-lactalbumin has two prominent forms: holo-state and apo-state. The holo-state is the natural form--folded and bound by calcium. The apo-state occurs in acidic conditions and is associated with the release of calcium ions and beta-sheet unfolding. 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. Alpha-LA is a Ca2+ binding protein with a single strong calcium binding spot seen below. The calcium binds to the carboxylic groups of three aspartate residues (Asp 82, 87, 88), seen in blue and to the carbonyl groups from lysine 79 and aspartate 84, seen in purple. This binding is coordinated by two water molecules (red). These residue binding sites are conserved among most species containing alpha-lactalbumin. Evolution The sequence comparison of α-lactalbumin shows a strong similarity to that of lysozymes, specifically the Ca2+-binding c-lysozyme. These two proteins share much of their physical structure but contain less than half of the same amino