Lactoperoxidase

• OMIM: 150 205
• UniProt: P22079
• MGI: 1923363

The enzyme lactoperoxidase (LPO ), is present in most animals and is excreted in man by the mammary glands, salivary glands, and mucous glands of the bronchi. It catalyzes the oxidation of phenols by hydrogen peroxide, and various anions. The reaction products are highly reactive molecules that are toxic to microorganisms have entered the body. LPO is therefore a part of the innate ( nonspecific ) immune system and allow the neutralization of bacteria in the milk or other mucosal secretions.

Under the lactoperoxidase system is understood to mean the combination of lactoperoxidase and its ionic substrates, hydrogen peroxide and the oxidation products. Known substrates are bromide and iodide ions as well as the thiocyanate ion. The products of the enzyme catalyzed oxidation are strong antibacterial activity, presumably by inhibition of glucose uptake.

• 4.1 Dental and Oral Health
• 4.2 Cystic Fibrosis
• 4.3 cancer

Structure

The structure of the lactoperoxidase is mainly composed of α - helices. There are also two short antiparallel β -sheets. A heme cofactor is located near the center of the apoprotein.

Function

The Lactoperoxidase catalyzes the oxidation of various oxygen acceptors by hydrogen peroxide ( H2O2):

• Reduced acceptor H2O2 → H2O oxidized acceptor

Examples of such oxidation reactions are:

• Thiocyanate ( SCN- ) → hypothiocyanite ( OSCN - )
• Bromide (Br - ) → hypobromite ( BrO )
• Iodide (I- ) → hypoiodite ( IO )

Source of hydrogen peroxide is often the reaction of glucose with oxygen in the presence of the enzyme glucose oxidase ( EC 1.1.3.4 ), which also takes place in the saliva. The glucose can turn in the presence of the salivary enzyme amyloglucosidase ( γ -amylase ( EC 3.2.1.3 ) ) arise from starch. Such oxidation products are highly reactive and strong antibacterial effect. The lactoperoxidase system is capable of a whole range of aerobic and anaerobic bacteria, including microaerophilic Helicobacter pylori. The effect of the lactoperoxidase system is dependent on specific experimental conditions. When bacteria are cultured under aerobic conditions on nutrient agar after they were exposed to the lactoperoxidase system, they do not grow. However, they grow very well on blood agar under anaerobic conditions. The lactoperoxidase system seems to act synergistically with lactoferrin and lysozyme. Is hydrogen peroxide in excess of thiocyanate present, the lactoperoxidase system can also act as cytotoxic.

Applications

Due to the antibacterial activity of the lactoperoxidase system, it is used for preserving food and cosmetics, and in ophthalmology. Further applications are in the fields of dentistry and the treatment of wounds. Perhaps the lactoperoxidase system can also be used to fight tumors and viruses.

Milk and milk products

The lactoperoxidase system inhibits the growth of the bacterial flora in the milk and milk products. The addition of hydrogen peroxide and a thiocyanate extended refrigerated shelf life of raw milk. The lactoperoxidase system is comparatively heat- stable and is used as an indicator of an over-pasteurization milk.

Dentistry

The lactoperoxidase system appears to be suitable and is therefore used as a component of tooth paste and mouthwashes for the treatment of dental caries, gingivitis and periodontitis. Because it inhibits the growth of bacteria in the oral cavity, it also inhibits acid production of these bacteria.

Clinical Significance of the lactoperoxidase system

Dental and Oral Health

In recent decades, a number of clinical studies on the effectiveness of the lactoperoxidase system in various oral hygiene products ( toothpastes, mouthrinses ) have been published. After having demonstrated indirectly through the measurement of experimental gingivitis and tooth decay parameter that mouthwashes which amyloglucosidase ( γ - amylase) and glucose oxidase contained activate the lactoperoxidase system, studies are known from recent times, the mechanism of the protective function light of enzymes in oral hygiene products. Enzymes such as lysozyme, lactoperoxidase and glucose oxidase are transmitted from the toothpastes of the pellicle. As part of the pellicle these enzymes are highly catalytically active. Similarly, the lactoperoxidase system as a component of toothpastes a favorable effect on the prevention of early childhood caries by reducing the number of educated colonies reduces cariogenic microflora, whilst increasing the thiocyanate concentration. Toothpastes with the lactoperoxidase system proved to xerostomia in patients compared to fluoride-containing toothpastes with regard to plaque formation and gingivitis as superior. Further studies of this nature should follow, not least in order to illuminate the mechanism of the protective effect in more detail, which is not yet precisely elucidated. The use of lactoperoxidase is not limited to dental caries, gingivitis and periodontitis. Thus, a combination of lysozyme and lactoperoxidase are also used to support the treatment of Burning Mouth Syndrome ( glossodynia ). In combination with lactoperoxidase, lactoferrin is effective against bad breath, in combination with lactoferrin and lysozyme carries lactoperoxidase for the relief of discomfort due to dryness of the mouth ( xerostomia) at. Similarly, gels with lactoperoxidase in oral cavity cancer patients whose salivary flow is restricted as a result of irradiation ( xerostomia), contribute to symptom relief and at the same time influence the bacterial flora favorable.

Cystic fibrosis

In the saliva of patients with cystic fibrosis have less thiocyanate is found than in healthy patients. Because so also less effective antibacterial hypothiocyanite can be formed, this could be a reason that these patients frequently suffer from respiratory diseases.

Cancer

Antibody conjugates with lactoperoxidase kill tumor cells. Macrophages were exposed to the lactoperoxidase may neutralize tumor cells increased. The oxidation of estradiol by lactoperoxidase is traded as a possible source of oxidative stress in breast cancer. Also, estrogen is oxidized in the presence of lactoperoxidase. This creates on the phenolic A- ring estrogen, a reactive phenoxy radical. By the action of lactoperoxidase could carcinogenic amines are activated so that they react more with DNA and thus contribute to the formation of breast cancer.