Lactoperoxidase

Lactoperoxidase is a is_associated_with::peroxidase is_associated_with::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 is_associated_with::gene.

Lactoperoxidase catalyzes the oxidation of a number of inorganic and organic substrates by is_associated_with::hydrogen peroxide. These substrates include is_associated_with::bromide and is_associated_with::iodide and therefore lactoperoxidase can be categorised as a is_associated_with::haloperoxidase. Another important substrate is is_associated_with::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 is_associated_with::innate immune system by killing bacteria in milk and is_associated_with::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 is_associated_with::breast cancer, through its ability to oxidize estrogenic hormones producing free radical intermediates.

Structure
The structure of lactoperoxidase consists mainly of alpha-helices plus two short antiparallel beta-strands and belongs to the heme peroxidase family of enzymes that also includes is_associated_with::myeloperoxidase (MPO), is_associated_with::eosinophil peroxidase (EPO), is_associated_with::thyroid peroxidase (TPO), and prostaglandin H synthase (PGHS). A is_associated_with::heme cofactor is bound near the center of the protein.

Function
Lactoperoxidase catalyzes the is_associated_with::hydrogen peroxide (H2O2) oxidation of several acceptor molecules:


 * reduced acceptor + H2O2 → oxidized acceptor + H2O

Specific examples include:


 * is_associated_with::thiocyanate (SCN−) → is_associated_with::hypothiocyanite (OSCN−)
 * is_associated_with::bromide (Br−) → is_associated_with::hypobromite (BrO−)
 * is_associated_with::iodide (I−) → hypoiodite (IO−)

Source of the is_associated_with::hydrogen peroxide (H2O2) usually is the reaction of is_associated_with::glucose with is_associated_with::oxygen in the presence of the enzyme is_associated_with::glucose oxidase that also takes place in is_associated_with::saliva. Glucose, in turn, can be formed from is_associated_with::starch in the presence of the saliva enzyme is_associated_with::amyloglucosidase.

These relatively short lived oxidized intermediates have potent is_associated_with::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 is_associated_with::lactoferrin and is_associated_with::lysozyme.

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 is_associated_with::gingivitis and is_associated_with::paradentosis. Lactoperoxidase has been used in toothpaste or a mouthrinse to reduce oral bacteria and consequently the acid produced by that bacteria.

Cosmetics
A combination of lactoperoxidase, glucose, is_associated_with::glucose oxidase (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 is_associated_with::herpes simplex virus and is_associated_with::human immunodeficiency virus.

Innate immune system
The antibacterial activity of lactoperoxidase plays an important role in the immune defense system.

is_associated_with::Hypothiocyanite is one of the reactive intermediates produced by the activity of lactoperoxidase on is_associated_with::thiocyanate and hydrogen peroxide produced by is_associated_with::dual oxidase 2 proteins, also known as Duox2. Thiocyanate secretion in is_associated_with::cystic fibrosis patients is decreased, resulting in a reduced production of the antimicrobial hypothiocyanite and consequently contributes to increased risk of airway infection.

The lactoperoxidase system efficiently inhibits is_associated_with::helicobacter pylori in buffer; however, in whole human saliva, it has a weaker antibacterial effect. The lactoperoxidase system does not attack DNA and is not mutagenic. 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.

Breast cancer
The oxidation of is_associated_with::estradiol by lactoperoxidase is a possible source of is_associated_with::oxidative stress in is_associated_with::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 is_associated_with::phenolic A-ring of is_associated_with::estrogens to produce reactive free radicals. 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.

Oral Care
During the last decades, several clinical studies describing the clinical efficacy of the lactoperoxidase system in a variety of oral care products (tooth pastes, mouth rinses) have been published. After showing indirectly, by means of measuring experimental is_associated_with::gingivitis and is_associated_with::caries parameters, that mouth rinses containing amyloglucosidase (γ-is_associated_with::amylase) and is_associated_with::glucose oxidase activate the lactoperoxidase system, the protective mechanism  of the enzymes in oral care products has been partially elucidated. Enzymes such as is_associated_with::lysozyme, lactoperoxidase and glucose oxidase are transferred from the tooth pastes to the pellicle. Being components of the pellicle, these enzymes are catalytically highly active. Also, as part of tooth pastes, the lactoperoxidase system has a beneficial influence to avoid early childhood caries by reducing the number of colonies formed by the cariogenic microflora while increasing the thiocyanate concentration. With is_associated_with::xerostomia patients, tooth pastes with the lactoperoxidase system are seemingly superior to is_associated_with::fluoride-containing tooth pastes with respect to plaque formation and gingivitis. More studies are required to examine further the protective mechanisms.

The application of lactoperoxidase is not restricted to caries, gingivitis, and is_associated_with::periodontitis. A combination of lysozyme and lactoperoxidase can be applied to support the treatment of the burning mouth syndrome (is_associated_with::glossodynia). In combination with lactoferrin, lactoperoxidase combats is_associated_with::halitosis; in combination with lactoferrin and lysozyme, lactoperoxidase helps to improve symptoms of xerostomia. Furthermore, gels with lactoperoxidase help to improve symptoms of oral cancer when saliva production is compromised due to irradiation. In this case, also the oral bacterial is_associated_with::flora are influenced favorably.