Lactoperoxidase
Encyclopedia
Lactoperoxidase is a peroxidase
enzyme
secreted from mammary, salivary, and other mucosal glands that functions as a natural antibacterial agent. Lactoperoxidase is a member of the heme peroxidase
family of enzymes. In humans, lactoperoxidase is encoded by the LPO gene
.
Lactoperoxidase catalyzes
the oxidation of a number of inorganic and organic substrates by hydrogen peroxide
. These substrates include bromide
and iodide
and therefore lactoperoxidase can be categorised as a haloperoxidase
. Another important substrate is thiocyanate
. The oxidized products produced through the action of this enzyme have potent bactericidal activities. Lactoperoxidase together with its inorganic ion substrates, hydrogen peroxide, and oxidized products is known as the lactoperoxidase system.
The lactoperoxidase system plays an important role in the innate immune system
by killing bacteria in milk and mucosal (linings of mostly endodermal origin, covered in epithelium, which are involved in absorption and secretion) secretions hence augmentation of the lactoperoxidase system may have therapeutic applications. Furthermore, addition or augmentation of the lactoperoxidase system has potential applications in controlling bacteria in food and consumer health care products. The lactoperoxidase system does not attack DNA and is not mutagenic. However, under certain conditions, the lactoperoxidase system may contribute to oxidative stress. Furthermore, lactoperoxidase may contribute to the initiation of breast cancer
, through its ability to oxidize estrogenic hormones producing free radical
intermediates.
plus two short antiparallel beta-strands
and belongs to the heme peroxidase family
of enzymes that also includes myeloperoxidase
(MPO), eosinophil peroxidase
(EPO), thyroid peroxidase
(TPO), and prostaglandin H synthase
(PGHS). A heme
cofactor is bound near the center of the protein.
(H2O2) oxidation of several acceptor molecules:
Specific examples include:
These relatively short lived oxidized intermediates have potent bactericidal effects, hence lactoperoxidase is part of the antimicrobial defense system in tissues that express lactoperoxidase. The lactoperoxidase system is effective in killing a range of aerobic
and certain anaerobic
microorganisms. Research (1984): "The effect of lactoperoxidase-thiocyanate-hydrogen peroxide mixtures on bacteria is dependent on experimental conditions. If the bacteria are cultured after the exposure to lactoperoxidase-thiocyanate-hydrogen peroxide on nutrient agar under aerobic conditions, they may not grow, whereas they grow readily on blood agar under anaerobic conditions." In its antimicrobial capacity, lactoperoxidase appears to acts synergistically with lactoferrin
and lysozyme
.
and paradentosis. Lactoperoxidase has been used in toothpaste or a mouthrinse to reduce oral bacteria and consequently the acid produced by that bacteria.
Several mouth rinses are claimed to contain enzymes such as lactoperoxidase to treat xerostomia
. However two tested mouth rinses with such claims were found to have no measurable peroxidase activity.
(GOD), iodide and thiocyanate is claimed to be effective in the preservations of cosmetics.
Peroxidase-generated hypothiocyanite inhibits herpes simplex virus
and human immunodeficiency virus.
secreted from salivary, mammary, and other mucosal glands that functions as a natural antibacterial agent. Hence it plays an important role in the immune defence system.
Hypothiocyanite
is one of the reactive intermediates produced by the activity of lactoperoxidase on thiocyanate
and hydrogen peroxyde produced by Dual oxidase 2 proteins, also known as Duox2. Thiocyanate secretion in cystic fibrosis
patients is decreased resulting in a reduced production of the antimicrobial hypothiocyanite and consequently contributes to the increased risk of airway infection.
The lactoperoxidase system efficiently inhibited helicobacter pylori
in buffer, however, in whole human saliva, it had a weaker antibacterial effect. The lactoperoxidase system did not attack DNA and was not mutagenic for any of the tested strains. However, under certain conditions, the lactoperoxidase system may contribute to oxidative stress. It has been shown that lactoperoxidase in the presence of thiocyanate can trigger the bactericidal and cytotoxic effects of hydrogen peroxide
under specific conditions, such as when hydrogen peroxide is present in the reaction mixtures in excess of thiocyanate.
by lactoperoxidase is a possible source of oxidative stress
in breast cancer
. The ability of lactoperoxidase to propagate a chain reaction leading to oxygen consumption and intracellular hydrogen peroxide accumulation could explain the hydroxyl radical-induced DNA base lesions recently reported in female breast cancer tissue. Lactoperoxidase may be involved in breast carcinogenesis, because of its ability to interact with estrogenic hormones and oxidise them through two one-electron reaction steps. Lactoperoxidase reacts with the phenol
ic A-ring of estrogen
s to produce reactive free radical
s. In addition, lactoperoxidase may activate carcinogenic aromatic and heterocyclic amines and increase binding levels of activated products to DNA, which suggests a potential role of lactoperoxidase-catalyzed activation of carcinogens in the causation of breast cancer.
Peroxidase
Peroxidases are a large family of enzymes that typically catalyze a reaction of the form:For many of these enzymes the optimal substrate is hydrogen peroxide, but others are more active with organic hydroperoxides such as lipid peroxides...
enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
secreted from mammary, salivary, and other mucosal glands that functions as a natural antibacterial agent. Lactoperoxidase is a member of the heme peroxidase
Animal heme-dependent peroxidases
Animal heme-dependent peroxidases is a family of peroxidases.Peroxidases are found in bacteria, fungi, plants and animals. On the basis of sequence similarity, a number of animal heme peroxidases can be categorized as members of a superfamily: myeloperoxidase ; eosinophil peroxidase ;...
family of enzymes. In humans, lactoperoxidase is encoded by the LPO 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...
.
Lactoperoxidase catalyzes
Catalysis
Catalysis is the change in rate of a chemical reaction due to the participation of a substance called a catalyst. Unlike other reagents that participate in the chemical reaction, a catalyst is not consumed by the reaction itself. A catalyst may participate in multiple chemical transformations....
the oxidation of a number of inorganic and organic substrates by hydrogen peroxide
Hydrogen peroxide
Hydrogen peroxide is the simplest peroxide and an oxidizer. Hydrogen peroxide is a clear liquid, slightly more viscous than water. In dilute solution, it appears colorless. With its oxidizing properties, hydrogen peroxide is often used as a bleach or cleaning agent...
. These substrates include bromide
Bromide
A bromide is a chemical compound containing bromide ion, that is bromine atom with effective charge of −1. The class name can include ionic compounds such as caesium bromide or covalent compounds such as sulfur dibromide.-Natural occurrence:...
and iodide
Iodide
An iodide ion is the ion I−. Compounds with iodine in formal oxidation state −1 are called iodides. This page is for the iodide ion and its salts. For information on organoiodides, see organohalides. In everyday life, iodide is most commonly encountered as a component of iodized salt,...
and therefore lactoperoxidase can be categorised as a haloperoxidase
Haloperoxidase
Haloperoxidases are peroxidases that are able to mediate the oxidation of halides by hydrogen peroxide. Both halides and hydrogen peroxide are widely available in the environment....
. Another important substrate is thiocyanate
Thiocyanate
Thiocyanate is the anion [SCN]−. It is the conjugate base of thiocyanic acid. Common derivatives include the colourless salts potassium thiocyanate and sodium thiocyanate. Organic compounds containing the functional group SCN are also called thiocyanates...
. The oxidized products produced through the action of this enzyme have potent bactericidal activities. Lactoperoxidase together with its inorganic ion substrates, hydrogen peroxide, and oxidized products is known as the lactoperoxidase system.
The lactoperoxidase system plays an important role in the innate immune system
Innate immune system
The innate immune system, also known as non-specific immune system and secondary line of defence, comprises the cells and mechanisms that defend the host from infection by other organisms in a non-specific manner...
by killing bacteria in milk and mucosal (linings of mostly endodermal origin, covered in epithelium, which are involved in absorption and secretion) secretions hence augmentation of the lactoperoxidase system may have therapeutic applications. Furthermore, addition or augmentation of the lactoperoxidase system has potential applications in controlling bacteria in food and consumer health care products. The lactoperoxidase system does not attack DNA and is not mutagenic. However, under certain conditions, the lactoperoxidase system may contribute to oxidative stress. Furthermore, lactoperoxidase may contribute to the initiation of breast cancer
Breast cancer
Breast cancer is cancer originating from breast tissue, most commonly from the inner lining of milk ducts or the lobules that supply the ducts with milk. Cancers originating from ducts are known as ductal carcinomas; those originating from lobules are known as lobular carcinomas...
, through its ability to oxidize estrogenic hormones producing free radical
Radical (chemistry)
Radicals are atoms, molecules, or ions with unpaired electrons on an open shell configuration. Free radicals may have positive, negative, or zero charge...
intermediates.
Structure
The structure of lactoperoxidase consists mainly of alpha-helicesAlpha helix
A common motif in the secondary structure of proteins, the alpha helix is a right-handed coiled or spiral conformation, in which every backbone N-H group donates a hydrogen bond to the backbone C=O group of the amino acid four residues earlier...
plus two short antiparallel beta-strands
Beta sheet
The β sheet is the second form of regular secondary structure in proteins, only somewhat less common than the alpha helix. Beta sheets consist of beta strands connected laterally by at least two or three backbone hydrogen bonds, forming a generally twisted, pleated sheet...
and belongs to the heme peroxidase family
Animal heme-dependent peroxidases
Animal heme-dependent peroxidases is a family of peroxidases.Peroxidases are found in bacteria, fungi, plants and animals. On the basis of sequence similarity, a number of animal heme peroxidases can be categorized as members of a superfamily: myeloperoxidase ; eosinophil peroxidase ;...
of enzymes that also includes myeloperoxidase
Myeloperoxidase
Myeloperoxidase is a peroxidase enzyme that in humans is encoded by the MPO gene. Myeloperoxidase is most abundantly expressed in neutrophil granulocytes . It is a lysosomal protein stored in azurophilic granules of the neutrophil...
(MPO), eosinophil peroxidase
Eosinophil peroxidase
Eosinophil peroxidase is a haloperoxidase enzyme that in humans is encoded by the EPX gene. The enzyme is a heterodimeric 71-77 kD peroxidase consisting of a heavier glycosylated chain and a lighter nonglycosylated chain...
(EPO), thyroid peroxidase
Thyroid peroxidase
Thyroid peroxidase or thyroperoxidase is an enzyme expressed mainly in the thyroid that liberates iodine for addition onto tyrosine residues on thyroglobulin for the production of thyroxine or triiodothyronine , thyroid hormones. In humans, thyroperoxidase is encoded by the TPO...
(TPO), and prostaglandin H synthase
Cyclooxygenase
Cyclooxygenase is an enzyme that is responsible for formation of important biological mediators called prostanoids, including prostaglandins, prostacyclin and thromboxane. Pharmacological inhibition of COX can provide relief from the symptoms of inflammation and pain...
(PGHS). A heme
Heme
A heme or haem is a prosthetic group that consists of an iron atom contained in the center of a large heterocyclic organic ring called a porphyrin. Not all porphyrins contain iron, but a substantial fraction of porphyrin-containing metalloproteins have heme as their prosthetic group; these are...
cofactor is bound near the center of the protein.
Function
Lactoperoxidase catalyzes the hydrogen peroxideHydrogen peroxide
Hydrogen peroxide is the simplest peroxide and an oxidizer. Hydrogen peroxide is a clear liquid, slightly more viscous than water. In dilute solution, it appears colorless. With its oxidizing properties, hydrogen peroxide is often used as a bleach or cleaning agent...
(H2O2) oxidation of several acceptor molecules:
- acceptor + H2O2 → oxidized acceptor + H2O
Specific examples include:
- thiocyanateThiocyanateThiocyanate is the anion [SCN]−. It is the conjugate base of thiocyanic acid. Common derivatives include the colourless salts potassium thiocyanate and sodium thiocyanate. Organic compounds containing the functional group SCN are also called thiocyanates...
(SCN–) → hypothiocyaniteHypothiocyaniteHypothiocyanite is the anion [OSCN]- and the conjugate base of hypothiocyanous acid. It is an organic compound part of the thiocyanates as it contains the functional group SCN. It is formed when an oxygen is singly bonded to the thiocyanate group...
(OSCN–) - bromideBromideA bromide is a chemical compound containing bromide ion, that is bromine atom with effective charge of −1. The class name can include ionic compounds such as caesium bromide or covalent compounds such as sulfur dibromide.-Natural occurrence:...
(Br–) → hypobromiteHypobromiteThe hypobromite ion, also called alkaline bromine water, is BrO−. Bromine is in the +1 oxidation state. Hypobromite is the bromine compound analogous to hypochlorites found in common bleaches, and in immune cells...
(BrO–) - iodideIodideAn iodide ion is the ion I−. Compounds with iodine in formal oxidation state −1 are called iodides. This page is for the iodide ion and its salts. For information on organoiodides, see organohalides. In everyday life, iodide is most commonly encountered as a component of iodized salt,...
(I–) → hypoioditeHypoiodous acidHypoiodous acid is formed when mercury oxide is shaken with aqueous iodine. It rapidly decomposes by disproportionation:Reactive solutions of hypoiodites can be prepared by reacting I2 with alkali hydroxides....
(IO–)
These relatively short lived oxidized intermediates have potent bactericidal effects, hence lactoperoxidase is part of the antimicrobial defense system in tissues that express lactoperoxidase. The lactoperoxidase system is effective in killing a range of aerobic
Aerobic organism
An aerobic organism or aerobe is an organism that can survive and grow in an oxygenated environment.Faculitative anaerobes grow and survive in an oxygenated environment and so do aerotolerant anaerobes.-Glucose:...
and certain anaerobic
Anaerobic organism
An anaerobic organism or anaerobe is any organism that does not require oxygen for growth. It could possibly react negatively and may even die if oxygen is present...
microorganisms. Research (1984): "The effect of lactoperoxidase-thiocyanate-hydrogen peroxide mixtures on bacteria is dependent on experimental conditions. If the bacteria are cultured after the exposure to lactoperoxidase-thiocyanate-hydrogen peroxide on nutrient agar under aerobic conditions, they may not grow, whereas they grow readily on blood agar under anaerobic conditions." In its antimicrobial capacity, lactoperoxidase appears to acts synergistically with lactoferrin
Lactoferrin
Lactoferrin , also known as lactotransferrin , is a multifunctional protein of the transferrin family. Lactoferrin is a globular glycoprotein with a molecular mass of about 80 kDa that is widely represented in various secretory fluids, such as milk, saliva, tears, and nasal secretions...
and lysozyme
Lysozyme
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...
.
Applications
Lactoperoxidase is an effective antimicrobial agent. Consequently applications of lactoperoxidase are being found in preserving food, cosmetics, and ophthalmic solutions. Furthermore lactoperoxidase have found application in dental and wound treatment. Finally lactoperoxidase may find application as anti-tumor and anti viral agents.Dairy products
Lactoperoxidase is an effective antimicrobial agent and is used as an antibacterial agent in reducing bacterial microflora in milk and milk products. Activation of the lactoperoxidase system by addition of hydrogen peroxide and thiocyanate extends the shelf life of refrigerated raw milk. It is fairly heat resistant and is used as an indicator of overpasteurization of milk.Oral care
A lactoperoxidase system is claimed to appropriate for the treatment of gingivitisGingivitis
Gingivitis is a term used to describe non-destructive periodontal disease. The most common form of gingivitis is in response to bacterial biofilms adherent to tooth surfaces, termed plaque-induced gingivitis, and is the most common form of periodontal disease...
and paradentosis. Lactoperoxidase has been used in toothpaste or a mouthrinse to reduce oral bacteria and consequently the acid produced by that bacteria.
Several mouth rinses are claimed to contain enzymes such as lactoperoxidase to treat xerostomia
Xerostomia
Xerostomia is the medical term for the subjective complaint of dry mouth due to a lack of saliva. Xerostomia is sometimes colloquially called pasties, cottonmouth, drooth, or doughmouth. Several diseases, treatments, and medications can cause xerostomia. It can also be exacerbated by smoking or...
. However two tested mouth rinses with such claims were found to have no measurable peroxidase activity.
Cosmetics
A combination of lactoperoxidase, glucose, glucose oxidaseGlucose oxidase
The glucose oxidase enzyme is an oxido-reductase that catalyses the oxidation of glucose to hydrogen peroxide and D-glucono-δ-lactone. In cells, it aids in breaking the sugar down into its metabolites....
(GOD), iodide and thiocyanate is claimed to be effective in the preservations of cosmetics.
Cancer and viral infections
Antibody conjugates of glucose oxidase and to lactoperoxidase have been found to effective in killing tumor cells in vitro. In addition, macrophages exposed to lactoperoxidase are stimulated to kill cancer cells.Peroxidase-generated hypothiocyanite inhibits herpes simplex virus
HIV
Human immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...
and human immunodeficiency virus.
Innate immune system
Lactoperoxidase is an oxidoreductaseOxidoreductase
In biochemistry, an oxidoreductase is an enzyme that catalyzes the transfer of electrons from one molecule to another...
secreted from salivary, mammary, and other mucosal glands that functions as a natural antibacterial agent. Hence it plays an important role in the immune defence system.
Hypothiocyanite
Hypothiocyanite
Hypothiocyanite is the anion [OSCN]- and the conjugate base of hypothiocyanous acid. It is an organic compound part of the thiocyanates as it contains the functional group SCN. It is formed when an oxygen is singly bonded to the thiocyanate group...
is one of the reactive intermediates produced by the activity of lactoperoxidase on thiocyanate
Thiocyanate
Thiocyanate is the anion [SCN]−. It is the conjugate base of thiocyanic acid. Common derivatives include the colourless salts potassium thiocyanate and sodium thiocyanate. Organic compounds containing the functional group SCN are also called thiocyanates...
and hydrogen peroxyde produced by Dual oxidase 2 proteins, also known as Duox2. Thiocyanate secretion in cystic fibrosis
Cystic fibrosis
Cystic fibrosis is a recessive genetic disease affecting most critically the lungs, and also the pancreas, liver, and intestine...
patients is decreased resulting in a reduced production of the antimicrobial hypothiocyanite and consequently contributes to the increased risk of airway infection.
The lactoperoxidase system efficiently inhibited helicobacter pylori
Helicobacter pylori
Helicobacter pylori , previously named Campylobacter pyloridis, is a Gram-negative, microaerophilic bacterium found in the stomach. It was identified in 1982 by Barry Marshall and Robin Warren, who found that it was present in patients with chronic gastritis and gastric ulcers, conditions that were...
in buffer, however, in whole human saliva, it had a weaker antibacterial effect. The lactoperoxidase system did not attack DNA and was not mutagenic for any of the tested strains. However, under certain conditions, the lactoperoxidase system may contribute to oxidative stress. It has been shown that lactoperoxidase in the presence of thiocyanate can trigger the bactericidal and cytotoxic effects of hydrogen peroxide
Hydrogen peroxide
Hydrogen peroxide is the simplest peroxide and an oxidizer. Hydrogen peroxide is a clear liquid, slightly more viscous than water. In dilute solution, it appears colorless. With its oxidizing properties, hydrogen peroxide is often used as a bleach or cleaning agent...
under specific conditions, such as when hydrogen peroxide is present in the reaction mixtures in excess of thiocyanate.
Breast cancer
The oxidation of estradiolEstradiol
Estradiol is a sex hormone. Estradiol is abbreviated E2 as it has 2 hydroxyl groups in its molecular structure. Estrone has 1 and estriol has 3 . Estradiol is about 10 times as potent as estrone and about 80 times as potent as estriol in its estrogenic effect...
by lactoperoxidase is a possible source of oxidative stress
Oxidative stress
Oxidative stress represents an imbalance between the production and manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage...
in breast cancer
Breast cancer
Breast cancer is cancer originating from breast tissue, most commonly from the inner lining of milk ducts or the lobules that supply the ducts with milk. Cancers originating from ducts are known as ductal carcinomas; those originating from lobules are known as lobular carcinomas...
. The ability of lactoperoxidase to propagate a chain reaction leading to oxygen consumption and intracellular hydrogen peroxide accumulation could explain the hydroxyl radical-induced DNA base lesions recently reported in female breast cancer tissue. Lactoperoxidase may be involved in breast carcinogenesis, because of its ability to interact with estrogenic hormones and oxidise them through two one-electron reaction steps. Lactoperoxidase reacts with the phenol
Phenol
Phenol, also known as carbolic acid, phenic acid, is an organic compound with the chemical formula C6H5OH. It is a white crystalline solid. The molecule consists of a phenyl , bonded to a hydroxyl group. It is produced on a large scale as a precursor to many materials and useful compounds...
ic A-ring of estrogen
Estrogen
Estrogens , oestrogens , or œstrogens, are a group of compounds named for their importance in the estrous cycle of humans and other animals. They are the primary female sex hormones. Natural estrogens are steroid hormones, while some synthetic ones are non-steroidal...
s to produce reactive free radical
Radical (chemistry)
Radicals are atoms, molecules, or ions with unpaired electrons on an open shell configuration. Free radicals may have positive, negative, or zero charge...
s. In addition, lactoperoxidase may activate carcinogenic aromatic and heterocyclic amines and increase binding levels of activated products to DNA, which suggests a potential role of lactoperoxidase-catalyzed activation of carcinogens in the causation of breast cancer.