Lactoperoxidase
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| Location (UCSC) | Chr 17: 58.22 – 58.27 Mb | Chr 11: 87.7 – 87.72 Mb | |||||||
| PubMed search | [3] | [4] | |||||||
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Lactoperoxidase is a peroxidase enzyme secreted from mammary, salivary and other mucosal glands including the lungs, bronchii and nose[5] that functions as a natural and the first line of defense against bacteria and viruses.[6] Lactoperoxidase is a member of the heme peroxidase family of enzymes. In humans, lactoperoxidase is encoded by the LPO gene.[7][8]
Lactoperoxidase
The lactoperoxidase system plays an important role in the
Structure
The structure of lactoperoxidase consists mainly of alpha-helices plus two short antiparallel beta-strands.[17] Lactoperoxidase belongs to the heme peroxidase family of mammalian 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.[18]
Function
Lactoperoxidase catalyzes the hydrogen peroxide (H2O2) oxidation of several acceptor molecules:[19]
- reduced acceptor + H2O2 → oxidized acceptor + H2O
Specific examples include:
- thiocyanate (SCN−) → hypothiocyanite (OSCN−)[20][21]
- bromide (Br−) → hypobromite (BrO−)
- iodide (I−) → hypoiodite (IO−)
Source of the
).These relatively short lived oxidized intermediates have potent
Applications
Lactoperoxidase is an effective antimicrobial and antiviral 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.[27] Lactoperoxidase has been used with radioactive iodine to selectively label membrane surfaces.[28]
Dairy products
Lactoperoxidase is an effective antimicrobial agent and is used as an antibacterial agent in reducing bacterial microflora in milk and milk products.[29] Activation of the lactoperoxidase system by addition of hydrogen peroxide and thiocyanate extends the shelf life of refrigerated raw milk.[19][30][31][32] It is fairly heat resistant and is used as an indicator of overpasteurization of milk.[33]
Oral care
A lactoperoxidase system is claimed to appropriate for the treatment of
Cosmetics
A combination of lactoperoxidase, glucose, glucose oxidase (GOD), iodide and thiocyanate is claimed to be effective in the preservations of cosmetics.[36]
Cancer
Antibody conjugates of glucose oxidase and to lactoperoxidase have been found to effective in killing tumor cells in vitro.[37] In addition, macrophages exposed to lactoperoxidase are stimulated to kill cancer cells.[38] Knockout mice deficient in lactoperoxidase suffer ill-health and develop tumors.[39]
Clinical significance
Innate immune system
The antibacterial and anti-viral activities of lactoperoxidase play an important role in the mammalian immune defense system; the lactoperoxidase system is considered the first line of defense against airborne bacteria and viral agents.[40][41][42] Importantly, lactoperoxidase is also extruded into the lung, bronchii and nasal mucus.[43]
Hypothiocyanite is one of the reactive intermediates produced by the activity of lactoperoxidase on thiocyanate and hydrogen peroxide produced by dual oxidase 2 proteins, also known as Duox2.[44][45] Thiocyanate secretion[46] in cystic fibrosis patients is decreased, resulting in a reduced production of the antimicrobial hypothiocyanite and consequently contributes to increased risk of airway infection.[47][48]
Viral infections
Peroxidase-generated hypoiodous acid (HOI), hypoiodite and hypothiocyanite all destroy the
Bacterial infections
The duox2-lactoperoxidase system has been shown to offer protection against many dozens of bacteria and mycoplasmas including varieties of the clinically important Staphylococcus and many Streptococcus types.[54] The lactoperoxidase system efficiently inhibits the common helicobacter pylori in buffer; however, in whole human saliva, it seems to have a weaker effect against this microbe.[55] It has been shown that lactoperoxidase in the presence of thiocyanide can catalyze the bactericidal and cytotoxic effects of hydrogen peroxide under specific conditions when hydrogen peroxide is present in excess of thiocyanide.[24] The combination of lactoperoxidase, hydrogen peroxide and thiocyanide is much more effective than hydrogen peroxide alone to inhibit bacterial metabolism and growth.[56]
Breast cancer
The oxidation of estradiol by lactoperoxidase is a possible source of oxidative stress in breast cancer.[15][16] 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.[15] 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.[16] Lactoperoxidase reacts with the phenolic A-ring of estrogens to produce reactive free radicals.[57] 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.[58]
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
The application of lactoperoxidase is not restricted to caries, gingivitis, and
See also
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000167419 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000009356 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ISBN 978-0-8247-7298-7.
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- ^ a b de Wit JN, van Hooydonk AC (1996). "Structure, functions and applications of lactoperoxidase in natural antimicrobial systems". Netherlands Milk & Dairy Journal. 50: 227–244.
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- ^ Harper WJ (2000). Biological properties of whey components a review. Chicago, IL: American Dairy Products Institute. p. 54.
- PMID 1112791.
- ^ Reiter B.; Härnulv BG. "The preservation of refrigerated and uncooled milk by its natural lactoperoxidase system". Dairy Ind. Int. 47 (5): 13–19.
- ^ Zajac M, Glandys J, Skarzynska M, Härnulv G, Eilertsen K (1983). "Milk quality preservation by heat treatment or activation of the lactoperoxidase system in combination with refrigerated storage". Milchwissenschaft. 38 (11).
- PMID 30921865.
- ^ Korhonen H (1980). "A new method for preserving raw milk: The lactoperoxidase antibacterial system". World Anim. Rev. 35: 23–29.
- .
- ^ WO application WO1988002600, Poulson OM, "Enzyme-containing bactericidal composition, and dental and wound treatment preparations comprising this composition", published 1988-04-21
- ISBN 978-0-8247-7298-7.
- ^ US 5607681, Galley E, Godfrey DC, Guthrie WG, Hodgkinson DM, Linnington HL, "Antimicrobial Compositions Containing Iodide, Thiocyanate, Glucose And Glucose Oxidase", published 1997-03-04, assigned to The Boots Company PLC
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Further reading
- Galijasevic S, Saed GM, Diamond MP, Abu-Soud HM (September 2004). "High dissociation rate constant of ferrous-dioxy complex linked to the catalase-like activity in lactoperoxidase". The Journal of Biological Chemistry. 279 (38): 39465–70. S2CID 30280587.
- Ekstrand B (1994). "Lactoperoxidase and lactoferrin". In Beuchat LR, Dillon VM, Board RG (eds.). Natural antimicrobial systems and food preservation. Oxon: CAB International. ISBN 978-0-85198-878-8.
- Kussendrager KD, van Hooijdonk AC (November 2000). "Lactoperoxidase: physico-chemical properties, occurrence, mechanism of action and applications". The British Journal of Nutrition. 84 (Suppl. 1): S19-25. PMID 11242442.
- Thomas EL, Pera KA, Smith KW, Chwang AK (February 1983). "Inhibition of Streptococcus mutans by the lactoperoxidase antimicrobial system". Infection and Immunity. 39 (2): 767–78. PMID 6832819.
- Korhonen H, Meriläinen V, Antila M, Kouvalainen K (1980). "[Antimicrobial factors in milk and infection resistance in infants]". Duodecim; Laaketieteellinen Aikakauskirja (in Finnish). 96 (3): 184–99. PMID 7192622.
- Oram JD, Reiter B (August 1966). "The inhibition of streptococci by lactoperoxidase, thiocyanate and hydrogen peroxide. The effect of the inhibitory system on susceptible and resistant strains of group N streptococci". The Biochemical Journal. 100 (2): 373–81. PMID 4290983.
- Oram JD, Reiter B (August 1966). "The inhibition of streptococci by lactoperoxidase, thiocyanate and hydrogen peroxide. The oxidation of thiocyanate and the nature of the inhibitory compound". The Biochemical Journal. 100 (2): 382–8. PMID 5338806.
- Hannuksela S, Tenovuo J, Roger V, Lenander-Lumikari M, Ekstrand J (1994). "Fluoride inhibits the antimicrobial peroxidase systems in human whole saliva". Caries Research. 28 (6): 429–34. PMID 7850846.
- Aune TM, Thomas EL (March 1978). "Oxidation of protein sulfhydryls by products of peroxidase-catalyzed oxidation of thiocyanate ion". Biochemistry. 17 (6): 1005–10. PMID 204336.
- Ekstrand B, Mullan WM, Waterhouse A (June 1985). "Inhibition of the Antibacterial Lactoperoxidase-Thiocyanate-Hydrogen Peroxide System by Heat-Treated Milk". Journal of Food Protection. 48 (6): 494–498. PMID 30943594.
- Reiter B, Härnulv G (September 1984). "Lactoperoxidase Antibacterial System: Natural Occurrence, Biological Functions and Practical Applications". Journal of Food Protection. 47 (9): 724–732. PMID 30934451.
External links
- Lactoperoxidase at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
