Alpha-lactalbumin is a prominent protein found in milk, particularly abundant in human breast milk, where it constitutes approximately 25-35% of the total protein content. It is a whey protein, meaning it remains soluble in milk after casein, another major milk protein, has curdled.
Structure and Biological Role
Alpha-lactalbumin possesses a unique globular structure, composed of 123 amino acid residues and four disulfide bridges, with a molecular weight of 14,178 Da. Its native structure is less stable than some similar proteins and depends heavily on a tightly bound calcium ion. This protein has two distinct forms: the holo-state, which is the natural, folded form bound by calcium, and the apo-state, which occurs under acidic conditions and involves the release of calcium ions and some unfolding.
The primary biological function of alpha-lactalbumin is its role in the synthesis of lactose, the main sugar in milk. It acts as a regulatory subunit of the enzyme lactose synthase, working in conjunction with galactosyltransferase (GT). In the mammary glands, alpha-lactalbumin enhances the affinity and specificity of GT for glucose, allowing the efficient transfer of galactose to glucose to form lactose. Alpha-lactalbumin also has a strong binding site for calcium ions, which can also bind other metal cations like magnesium, manganese, sodium, and potassium, and it contains several distinct zinc-binding sites. The binding of these cations influences the protein’s stability and interactions with other molecules, including membranes, proteins, peptides, and various substrates and products.
Importance in Infant Development
Alpha-lactalbumin offers significant nutritional value for infants due to its rich composition of essential amino acids, which are necessary for proper growth and development. It has a balanced amino acid profile, including high levels of tryptophan, lysine, cysteine, and branched-chain amino acids like leucine, isoleucine, and valine.
The protein’s high digestibility and bioavailability mean it is easily broken down and absorbed by an infant’s immature digestive system, allowing for efficient utilization of its nutrients. This easy digestion contributes to better gastrointestinal tolerance in infants, with studies suggesting that formulas enriched with alpha-lactalbumin can reduce instances of abdominal pain, constipation, vomiting, and regurgitation, making them more comparable to breastfed infants. Alpha-lactalbumin also supports the development of a healthy gut microbiome by increasing beneficial bacteria like bifidobacteria and potentially inhibiting the growth of pathogens, which may offer enhanced protection against infections such as E. coli-induced diarrhea.
Applications and Health Considerations
Alpha-lactalbumin is frequently incorporated into infant formulas, especially those designed to more closely resemble the protein composition of human milk. By enriching formulas with bovine alpha-lactalbumin, which has a similar amino acid profile to human alpha-lactalbumin, manufacturers can lower the overall protein content. This helps meet an infant’s amino acid requirements, supporting age-appropriate growth and potentially reducing the risk of later childhood obesity.
Beyond infant nutrition, alpha-lactalbumin is also found in some dietary supplements, particularly those aimed at sports nutrition or general wellness, owing to its high content of branched-chain amino acids like leucine, which supports muscle protein synthesis. A complex formed between partially unfolded alpha-lactalbumin and oleic acid, known as HAMLET (Human Alpha-lactalbumin Made LEthal to Tumor cells), has demonstrated the ability to induce cell death in various tumor cells while sparing healthy cells in laboratory and animal studies. This complex is being investigated for its potential anti-cancer properties and has shown therapeutic efficacy in models of skin papillomas and bladder cancer.
Alpha-lactalbumin is also being studied for its potential influence on sleep and stress, due to its high tryptophan content. Tryptophan is a precursor to serotonin and melatonin, neurotransmitters and hormones that regulate sleep-wake cycles and mood. Studies suggest that consuming alpha-lactalbumin can increase the ratio of tryptophan to other amino acids in the plasma, potentially leading to increased brain serotonin activity, reduced sleepiness, and improved attention, especially in individuals with mild sleep complaints or under stress.
Despite its benefits, alpha-lactalbumin can be a concern for individuals with cow’s milk allergy. It is one of the whey proteins, along with beta-lactoglobulin, that can trigger allergic reactions in sensitive individuals, though casein is also a common allergen. Symptoms can range from skin issues like hives and eczema to gastrointestinal problems such as vomiting, diarrhea, or constipation, and in rare cases, more severe systemic reactions. Unlike casein, alpha-lactalbumin is generally heat-sensitive, meaning some individuals with an allergy to this protein might tolerate extensively heated or baked milk products, as the heating process can alter its structure and reduce its allergenicity.