lysozyme (LYZ)

see also:

• the GIT microbiome
• innate immunity
• atherosclerosis and primary prevention

• lysozyme (LYZ) plays an important role in bacterial lysis, by hydrolyzing the glycosidic bond between N-acetylmuramic acid and N-acetylglucosamine and destroying the peptidoglycan (PG)-rich cell walls of gram-positive bacteria
• the C-type LYZ is predominantly expressed in chordates and different classes of Arthropoda
• LYZ C-1, also known as 1,4-β-N-acetylmuramidase C or LYZ C-type P, is encoded by the lysozyme 1 gene (Lyz1), which is orthologous to human LYZ and is involved in the defense response to gram-positive and gram-negative bacteria ¹⁾
  • can also break glycosidic bonds in chitin, although not as effectively as true chitinases
  • it also has a non-enzymic lectin-like ability of lysozyme to recognize bacterial carbohydrate antigen without lytic activity was reported for tetrasaccharide related to lipopolysaccharide of Klebsiella pneumoniae.
  • C-type lysozymes are closely related to α-lactalbumin in sequence and structure, making them part of the same glycoside hydrolase family 22
  • defensins and lysozyme amongst many other roles are the main first line defenses of the conjunctiva via tears and both play central roles in neonate immunity via human breast milk
  • it has the highest expression in adult large and small intestines but is also abundant in other secretions including tears, saliva, human milk, and mucus.
  • LYZ can be secreted by the epithelium, neutrophils, or macrophages and subsequently delivered to bacterium-containing phagosomes
  • the epithelium secretes LYZ to kill bacteria at the site of infection and facilitates the release of pathogen-associated molecular patterns, including monomeric PG
  • extracellular insoluble PG elicits potent phagocyte chemotaxis via the complement pathway
  • LYZ activates pro-inflammatory immune responses in multiple ways, and failure to clear PG by LYZ can drive increased inflammation
  • LYZ also drives an anti-inflammatory response to alleviate inflammatory-driven pathology and limit inflammation
  • LYZ enzymic activity increases with increasing temperatures, up to 60 degrees Celsius

• LYZ is a key regulatory factor of gut microbiota
• intestinal inflammation reportedly correlates with LYZ P deficiency, with LYZ mutation causing gastrointestinal, renal, and hepatic symptoms
• LYZ deficiency drives vascular aging via gut dysbiosis via PI3K-Akt suppression and Lyz1 could be used as a marker for vascular aging
  • oral lysozyme (LYZ) appears to restore gut balance and reverse vascular inflammatory aging phenotypes in mice ²⁾

• large amounts of lysozyme can be found in egg white and in human breast milk and non-pasteurised milks
  • hen egg white lysozyme is thermally stable, with a melting point reaching up to 72°C and maintains its activity in a large range of pH (6–9)
  • the concentration of lysozyme in human milk is 1,600 to 3,000 times greater than the concentration in livestock milk and is more active than hen egg white lysozyme, however, lysozyme in human milk loses activity very quickly on heating to 72°C
    • it plays an important role in immunology of infants in human milk feeding
      • a transgenic line of goats (with a founder named “Artemis”) were developed to produce milk with human lysozyme to protect children from diarrhea if they can't get the benefits of human breastfeeding
  • some digestive lysozyme variants (e.g., those found in certain animals like cows) are structurally adapted to be more resistant to acidic pH and proteolytic enzymes than the lysozyme in egg white or human milk, maintaining activity in the stomach and gut however even the lysozyme of egg white and human milk will generally have some activity after passing the stomach
  • pasteurization of cow's milk significantly reduces or destroys lysozyme activity and it drops dramatically, often to undetectable levels.
• supplemental encapsulated oral lysozyme formulations

• excessive production of lysozyme by cancer cells in certain cancers (especially myelomonocytic leukemia) can lead to toxic levels of lysozyme in the blood
• high lysozyme blood levels can lead to kidney failure and hypokalaemia, conditions that may improve or resolve with treatment of the primary malignancy
• serum LYZ levels are more sensitive than ACE as a marker of sarcoidosis disease activity (but is much less specific) and is suitable for disease monitoring in proven cases
• IV lysozyme administration appears to increase inflammation