MUDr. Dana Maňasková

  • medicinman.cz
  • Zájmy a činnosti
  • Nemoci a symptomy
  • Léky, látky a laboratorní testy
  • Postupy, metody a terapie
  • Dietologie a potravinářství
  • P-o-traviny, rostliny aj.
  • Papírování
  • Zajímaví lidé a činnosti
  • Odborná pracoviště
  • Odborné odkazy
  • Obecné odkazy a tipy
  • Kalendář akcí
  • CV a kredity
  • Fantazie, nápady a snění
  • GDPR

Vyhledávání na medicinman.cz
 

Význam

Conversion of prostaglandin H2

  • A metabolite of arachidonic acid into prostaglandins D2 and E2 by endoperoxide isomerase [1]

GSH inhibits infection

  • By the influenza virus [1]

Glutathione peroxidase - GPx

  • Catalyzed by the reaction catalyzed by the reduced form of glutathione (GSH)
    • By reacting with hydrogen peroxide or lipid peroxides
      • While playing a role in the detoxification of these molecules by creating a glutathione bridge with another glutathione molecule (GSSG) form
  • H2O2 is detoxified by catalase and glutathione peroxidase
  • Glutathione redox cycle plays a key role in the reduction of intracellular hydroperoxides
  • GPx belongs to the class of selenocysteine compound
  • It binds four atoms of selenium
  • Provides the catalytic activity of glutathione peroxidase
  • It needs glutathione as a co-substrate
  • www.intechopen.com/books/glutathione-system-and-oxidative-stress-in-health-and-disease/glutathione-peroxidase-in-health-and-diseases
  • Glutathione peroxidase (GSH-Px; E.C. 1.11.1.9)
  • Cytosolic enzyme
  • Reduction of hydroperoxides
  • In erythrocytes, GSH-Px is the most effective antioxidant against oxidant stress
    • Has some important functions in phagocytic cells
  • Most effective enzyme in endothelial cells and especially in the lung !!!
  • Cca 60–75% of enzyme activity is found in the eukaryotic cell cytoplasm
  • Cca 25–40% activity is found in mitochondria
  • The most common enzyme activity is clear in erythrocytes and liver
  • GPx is the most important enzyme that protects lipids from peroxidation at intracellular distance
    • Maintains the structure and function of the cell
  • www.intechopen.com/books/glutathione-system-and-oxidative-stress-in-health-and-disease/glutathione-peroxidase-in-health-and-diseases
  • GSH-Px is also involved in the detoxification of xenobiotics
  • Provides the most vital defense against the peroxidative damage of biological membranes in mammalian cells
    • Glutathione peroxidase, catalase, and superoxide dismutase together
      • Form a common system aimed at protecting the cell from peroxidant molecules
  • Inhibition of ferroptosis by GPx4 provides protective mechanisms against neurodegeneration.
    • selenium deficiency increases susceptibility to ferroptotic processes and other programmed cell death pathways due to a decrease in GPx activity
  • Reduction of peroxides, which inactivate vasodilating NO
  • Decomposition of S-nitrosoglutathione (GSNO)
    • Important role in vascular homeostasis
  • H202 difunduje přes membrány a reaguje přednostně se sloučeninami obsahujícími thiol, které iniciují redox signalizace.
  • cs.ulfsciences.com/nadph-oxidases-ros-signaling-gastrointestinal-tract-560408

Decreased GPx activity

    • Causes hepatocellular degeneration and premature death of mice.
  • Since many harmful conditions are known to directly disrupt the GPx
    • Inhibition of ferroptosis may represent a suitable therapeutic approach to improve hepatocyte cell death.
  • GPx is particularly vulnerable to the oxidative stress associated with hypertension.
  • www.intechopen.com/books/glutathione-system-and-oxidative-stress-in-health-and-disease/glutathione-peroxidase-in-health-and-diseases

GPx1 deficiency

  • Led to endothelial dysfunction,
  • Impaired angiogenesis,
  • Increased infarction size and vascular permeability following ischemia/reperfusion injury

Glutathionylation of proteins

  • Thioredoxin, ubiquitin-conjugating enzyme, and cytochrome c oxidase
    • Plays an important role in cell physiology [1]

Glyoxalase system

  • Converts methylglyoxal to d-lactate
    • A pathway active in microorganisms [1]

Imunita

  • Essential for the activation of T-lymphocytes and polymorphonuclear leukocytes
    • As well as for cytokine production
      • For mounting successful immune responses when the host is immunologically challenged [1]

Keeping sulfhydryl groups in proteins in the reduced state

  • Funkce proteinů - tvar ve 3D cestou -S-S- vazeb !!!

Glutathion + NO

  • Exposure of human neutrophils to NO
    • Results in the conversion of intracellular GSH to GSNO
    • Intracellular GSNO activates the hexose monophosphate shunt of the cells
  • Since GSH concentration is millimolar in cells and NO concentration is less than micromolar
    • It follows that the concentration of GSNO will always be small compared that of GSH.
  • Addition to release of NO from GSNO in the presence of GSH
    • Important pathway for GSNO decomposition is reaction with GSH to form glutathione conjugates
      • Similar to those reported for the reaction of GSH with other electrophilic metabolites
  • Major end product from this transformation is oxidized GSH, GSSG
    • Amount formed is dependent on the availability of oxygen in the system
      • Suggesting the possible involvement of radicals.
  • NO was being released from GSNO in the presence of GSH
    • GSH conjugation is believed to be one of the primary detoxification mechanisms in vivo.
  • www.pnas.org/content/93/25/14428

<2>Oxidace GSH
  • Shifting the GSH/GSSG redox toward the oxidizing state activates several signaling pathways including
    • protein kinase B,
    • protein phosphatases 1 and 2A,
    • Calcineurin = antivirový
    • Nuclear factor ?B,
    • C-Jun N-terminal kinase
    • Apoptosis signal-regulated kinase 1
    • Mitogen-activated protein kinase
  • Thereby reducing cell proliferation and increasing apoptosis = antivirové...

Phospholipid hydroperoxide glutathione peroxidase (PLGSH-Px)

  • Reduces membrane phospholipid hydroperoxides to alcohol
  • Also contains the Se atom and is monomeric
  • It is also a cytosolic enzyme
  • PLGSH-Px provides protection against peroxidation of the membrane
    • In cases where vitamin E, a membrane-bound antioxidant, is insufficient
  • Glutathione peroxidase catalyzes detoxification of H2O2 and lipid peroxides by reduced glutathione.
  • Thus, it protects membrane lipids and hemoglobin from oxidation of peroxides

Proliferace

  • Adequate GSH concentrations are necessary for the proliferation of cells, including
    • Lymphocytes
    • Intestinal epithelial cells

Spermatogenesis and sperm maturation



Substrate for formaldehyde dehydrogenase

  • Converts formaldehyde and GSH to S-formyl-glutathione
  • Removal of formaldehyde (a carcinogen) is of physiological importance
    • Because it is produced from the metabolism of:
      • methionine,
      • Choline,
      • Methanol (alcohol dehydrogenase)
      • Sarcosine (sarcosine oxidase)
      • Xenobiotics (via the cytochrome P450-dependent monooxygenase system of the endoplasmic reticulum) [1]

Vitiligo

  • Significant relationship between low GPx level and vitiligo.

Vychytávač volných radikálů

  • The most important antioxidant molecule of intracellular environment
  • GSH effectively scavenges free radicals and other reactive oxygen species
    • Hydroxyl radical, lipid peroxyl radical, peroxynitrite, and H2O2
  • Directly, and indirectly through enzymatic reactions
  • GSH is oxidized to form GSSG
    • Then reduced to GSH by the NADPH-dependent glutathione reductase
  • Glutathione peroxidase (a selenium-containing enzyme)
    • catalyzes the GSH-dependent reduction of H2O2 and other peroxides [1]
  • Most abundant cytosolic thiol
  • Important roles in the non-enzymatic antioxidant defence system
  • Free radical scavenging activity
    • ·OH, ·OOH, ·OCH3, ·OOCH3, ·OOCHCH2 and ·OOCCl3
  • Reacts exclusively by H transfer
  • With the exception of its reaction with ·OH there is only one important channel of reaction, yielding to the S-centered radical
  • Exceptionally good as a OOH radical scavenger
    • Comparable to 2-propenesulfenic acid
    • Strong H bonding interactions found in the transition states, which involves the carboxylate moiety
  • pubs.rsc.org/en/content/articlelanding/2011/ra/c1ra00474c#!divAbstract

Redoxní cyklus

  • Glutathione, in reduced form (GSH), turns itself into oxidized glutathione (GSSG) form with creating disulfide bridge with another glutathione molecule
    • While playing role in detoxification of these molecules by reacting with hydrogen peroxides or lipid peroxides, with the reaction catalyzed by the GPx enzyme
  • For the maintenance of free radical detoxification in cell, GSSG needs to be converted back to the reduced form
  • GSSG is converted to reduced glutathione form with GR enzyme by a reaction in which NADPH is used

GSH conjugates with NO

  • To form an S-nitroso-glutathione adduct
    • Cleaved by the thioredoxin system to release GSH and NO
  • Recent evidence suggests that the targeting of endogenous NO is mediated by intracellular GSH
  • Both NO and GSH are necessary for the hepatic action of insulin-sensitizing agents
    • Indicating their critical role in regulating lipid, glucose, and amino acid utilization [1]

GSH reacts with various electrophiles, physiological metabolites

  • Estrogen,
  • Melanins,
  • Prostaglandins,
  • Leukotrienes
  • Bromobenzene
  • Acetaminophen
  • To form mercapturates
    • Initiated by glutathione-S-transferase (a family of Phase II detoxification enzymes) [1]

Indikace

  • Glutathion se používá při
    • Alzheimerově
    • Parkinsonově chorobě
    • šedém a zeleném zákalu
    • alkoholizmu
    • Prevenci stárnutí
    • Astmatu
    • Nádorových onemocněních
    • Kardiovaskulárních chorobách (ateroskleróze a hypercholesterolemii)
    • žloutenkách a onemocnění jater
    • Snížené imunitě (včetně AIDS a chronickém únavovém syndromu)
    • Ztrátě paměti
    • Zánětech pohybového ústrojí
    • Detoxikaci těžkých kovů
    • Pro snížení toxického účinku některých léčiv (cisplatiny)
  • www.uspesna-lecba.cz/glutathion/

Popisované účinky

  • Zlepšuje cévní prokrvení všech orgánů
  • Snižuje riziko vzniku trombóz
  • Zlepšuje činnost a zvyšuje výkon srdce
  • Potlačuje vznik a rozvoj nemocí trávicího traktu například žaludečních vředů, Crohnovy choroby, onemocnění slinivky ...
  • Zvyšuje citlivost na inzulín
  • Nefroprotektivní
  • Zlepšuje stav nervového systému, zlepšuje průběh nervových i psychických onemocnění
  • Zlepšuje stav arteriosklerotických změn (například mozkových cév)
  • Neutralizuje toxické látky jako jsou těžké kovy, nejrůznější toxická farmaka, ale také následky elektromagnetického záření a UV záření
  • Protinádorový účinek
  • Prodlužuje život a chrání tělo před předčasným stárnutím
  • L-Glutathion není toxický ani ve vysokých dávkách
  • www.uspesna-lecba.cz/glutathion/

Význam glutathionu

  • Concentrations of reduced glutathione (GSH) in most cell types highlights its vital and multifunctional roles in the control of various biological processes such as
    • Detoxification of foreign and endogenous compounds,
    • protein folding,
    • Regeneration of vitamins C and E,
    • Maintenance of mitochondrial function,
    • Antiviral defense,
    • Regulation of cellular proliferation, apoptosis,
    • Immune response
O úroveň výše

Poslední aktualizace: 4. 11. 2020 21:32:35
© Dana Maňasková, metabalance.cz
e-mail