Alpha-lactalbumin
Encyclopedia
Lactalbumin, alpha-, also known as LALBA, is a protein
that in humans is encoded by the LALBA gene
.
in cow's milk
(~1 g/l), and is also present in the milk of many other mammal
ian 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 patients 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.
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
.
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.
s, 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.
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
that in humans is encoded by the LALBA gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
.
Function
α-Lactalbumin is an important whey proteinWhey protein
Whey protein is a mixture of globular proteins isolated from whey, the liquid material created as a by-product of cheese production. Some preclinical studies in rodents have suggested that whey protein may possess anti-inflammatory or anti-cancer properties; however, human data is lacking...
in cow's milk
Milk
Milk is a white liquid produced by the mammary glands of mammals. It is the primary source of nutrition for young mammals before they are able to digest other types of food. Early-lactation milk contains colostrum, which carries the mother's antibodies to the baby and can reduce the risk of many...
(~1 g/l), and is also present in the milk of many other mammal
Mammal
Mammals are members of a class of air-breathing vertebrate animals characterised by the possession of endothermy, hair, three middle ear bones, and mammary glands functional in mothers with young...
ian species. In primates, alpha-lactalbumin expression is upregulated in response to the hormone prolactin
Prolactin
Prolactin also known as luteotropic hormone is a protein that in humans is encoded by the PRL gene.Prolactin is a peptide hormone discovered by Henry Friesen...
and increases the production of lactose
Lactose
Lactose is a disaccharide sugar that is found most notably in milk and is formed from galactose and glucose. Lactose makes up around 2~8% of milk , although the amount varies among species and individuals. It is extracted from sweet or sour whey. The name comes from or , the Latin word for milk,...
.
α-Lactalbumin forms the regulatory subunit of the lactose synthase
Lactose synthase
Lactose synthase is an enzyme that generates lactose from glucose and UDP-galactose.It is classified under .It consists of N-acetyllactosamine synthase and alpha-lactalbumin...
(LS) heterodimer and β-1,4-galactosyltransferase
B4GALT1
Beta-1,4-galactosyltransferase 1 is an enzyme that in humans is encoded by the B4GALT1 gene.-External links:*...
(beta4Gal-T1) forms the catalytic component. Together, these proteins enable LS to produce lactose
Lactose
Lactose is a disaccharide sugar that is found most notably in milk and is formed from galactose and glucose. Lactose makes up around 2~8% of milk , although the amount varies among species and individuals. It is extracted from sweet or sour whey. The name comes from or , the Latin word for milk,...
by transferring galactose
Galactose
Galactose , sometimes abbreviated Gal, is a type of sugar that is less sweet than glucose. It is a C-4 epimer of glucose....
moieties to glucose
Glucose
Glucose is a simple sugar and an important carbohydrate in biology. Cells use it as the primary source of energy and a metabolic intermediate...
. 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
HAMLET (human alpha-lactalbumin made lethal to tumor cells)
HAMLET is a complex between alpha-lactalbumin and oleic acid that induces apoptosis in tumor cells, but not in healthy cells....
, probably induces apoptosis
Apoptosis
Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...
in tumor and immature cells.
Research by a Dr. Vincent Tuohy at the Cleveland Clinic
Cleveland Clinic
The Cleveland Clinic is a multispecialty academic medical center located in Cleveland, Ohio, United States. The Cleveland Clinic is currently regarded as one of the top 4 hospitals in the United States as rated by U.S. News & World Report...
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 patients 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.
When formed into a complex with Gal-T1, a galactosyltransferase
Galactosyltransferase
Galactosyltransferase is a type of glycosyltransferase which catalyzes the transfer of galactose. An example is B-N-acetylglucosaminyl-glycopeptide b-1,4-galactosyltransferase....
, α-lactalbumin, enhances the enzyme's affinity for glucose
Glucose
Glucose is a simple sugar and an important carbohydrate in biology. Cells use it as the primary source of energy and a metabolic intermediate...
by about 1000 times, and inhibits the ability to polymerise multiple galactose
Galactose
Galactose , sometimes abbreviated Gal, is a type of sugar that is less sweet than glucose. It is a C-4 epimer of glucose....
units. This gives rise to a pathway for forming lactose
Lactose
Lactose is a disaccharide sugar that is found most notably in milk and is formed from galactose and glucose. Lactose makes up around 2~8% of milk , although the amount varies among species and individuals. It is extracted from sweet or sour whey. The name comes from or , the Latin word for milk,...
by converting Gal-TI to Lactose synthase
Lactose synthase
Lactose synthase is an enzyme that generates lactose from glucose and UDP-galactose.It is classified under .It consists of N-acetyllactosamine synthase and alpha-lactalbumin...
.
Physical properties
The molecular weight is 14178 Da, and the isoelectric pointIsoelectric point
The isoelectric point , sometimes abbreviated to IEP, is the pH at which a particular molecule or surface carries no net electrical charge....
is between 4.2 and 4.5. One of the main structural differences with beta-lactoglobulin
Beta-lactoglobulin
right|thumbnail|300px|Structure of a β-lactoglobulin subunit Ribbons denote the [[secondary structure]], with arrows for beta strands and spirals for alpha-helices. Rendered with [[Kinemage]]...
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
Denaturation (biochemistry)
Denaturation is a process in which proteins or nucleic acids lose their tertiary structure and secondary structure by application of some external stress or compound, such as a strong acid or base, a concentrated inorganic salt, an organic solvent , or heat...
and acidification.
Evolution
The sequence comparison of α-lactalbumin shows a strong similarity to that of lysozymeLysozyme
Lysozyme, also known as muramidase or N-acetylmuramide glycanhydrolase, are glycoside hydrolases, enzymes that damage bacterial cell walls by catalyzing hydrolysis of 1,4-beta-linkages between N-acetylmuramic acid and N-acetyl-D-glucosamine residues in a peptidoglycan and between...
s, 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.