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  • Carbonic Anhydrase

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    Harshal Jadhav
    32 vizualizări28 pagini
    Carbonic anhydrase catalyzes the reaction of carbon dioxide and water to form bicarbonate. It contains about 0.31-0.34% zinc, which is important as it represents the first known direct physiological function of zinc. Zinc is well-suited for its role in carbonic anhydrase for several reasons: as Zn2+ it is not redox active, it can bind both hard and soft ligands, and prefers a tetrahedral geometry allowing coordination of 5-6 ligands. Carbonic anhydrase inhibitors containing zinc are used to treat glaucoma by reducing pressure built up inside the eye.

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    this document gives information about carbonic anhydrase,its background,mechanism role of zinc

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    Carbonic anhydrase catalyzes the reaction of carbon dioxide and water to form bicarbonate. It contains about 0.31-0.34% zinc, which is important as it represents the first known direct physiological function of zinc. Zinc is well-suited for its role in carbonic anhydrase for several reasons: as Zn2+ it is not redox active, it can bind both hard and soft ligands, and prefers a tetrahedral geometry allowing coordination of 5-6 ligands. Carbonic anhydrase inhibitors containing zinc are used to treat glaucoma by reducing pressure built up inside the eye.

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    32 vizualizări28 pagini

    Carbonic Anhydrase

    Încărcat de

    Harshal Jadhav
    Carbonic anhydrase catalyzes the reaction of carbon dioxide and water to form bicarbonate. It contains about 0.31-0.34% zinc, which is important as it represents the first known direct physiological function of zinc. Zinc is well-suited for its role in carbonic anhydrase for several reasons: as Zn2+ it is not redox active, it can bind both hard and soft ligands, and prefers a tetrahedral geometry allowing coordination of 5-6 ligands. Carbonic anhydrase inhibitors containing zinc are used to treat glaucoma by reducing pressure built up inside the eye.

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    din 28

    CARBONIC

    ANHYDRASE:
    WhyZinc?
    By:AmirSafi

    WhatReactionis
    Catalyzed?
    H2O+CO2

    +
    H

    +HCO3

    CarbonicAnhydrase CatalyzestheReactionofwater+carbondioxidetoformbicarbonate.

    Rate of Catalysis
    CO2 + H2O = HCO3- + H+

    -11
    -1
    10 s

    kuncat =
    4
    -1
    kcat = 10 s

    Role of Zn(II) in Proteins

    1. Catalytic: involved directly in catalytic steps


    (e.g., CA)

    2. Structural: required for the stability of a protein structure, or


    arrangement of an active site
    (e.g., CuZnSOD)

    3. Regulatory: Zn-free enzyme has activity, addition of Zn2+


    enhance or inhibit activity
    (e.g., zinc finger family of proteins)

    Zinc Fingers

    Cys2His2 zinc fingers are found in 2% of all human genes


    Jamieson, Andrew C.; Miller, Jeffrey C.; Pabo, Carl O. Nature Rev. Drug Discovery (2003), 2, 361-368.

    Hydrolytic reactions

    Hydrolytic reactions

    BackgroundonCarbonic
    Anhydrase
    CarbonicAnhydrase isanenzymethatis
    locatedinredbloodcells.
    Itcontainsabout.31to.34%zinc.
    Thisisimportantbecauseitsthefirstknown
    directphysiologicalfunctionofzinc.
    http://www.pdb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/pdb49_1.
    html

    CarbonAnhydrase Mechanism

    Step1:deprotonation

    1.Berg,JeremyM.(2007).Biochemistry,6thEd.

    Step2:Carboxylation
    Theanionicoxygenthen
    performsanucleophilic
    attackonthecarbon.

    Step3:FormationofRingStructure
    AnionicoxygenformsabondwithZn2+tomakearinglike
    resonance.

    Step4:FormationofBicarbonate
    Additionofwater
    displacesthe
    bicarbonateion.

    CarbonicAnhydrase Mechanism

    BIGQUESTION:
    WHYDOESCARBONANHYDRASEUSE
    ZINC?

    HistoryofZinc
    Zinccompoundshavebeenusedforatleast
    2,500years
    Zincderiveditsname,supposedly,fromthe
    Germanword Zinke,whichmeans'toothlike'
    or'pointed'.
    MetalliczincwasfirstproducedinIndia
    sometimeinthe1400sbyheatingthemineral
    calamine(ZnCO3)withwool.
    ZincwasrediscoveredbyAndreasSigismund
    Marggraf in1746byheatingcalaminewith
    charcoal.

    http://www.buzzle.com/articles/historyofzinc.html

    Fe,Zn,Cu:themostcommon
    transitionmetalionsinbiology
    ELEMENT

    Sea Water(M)x10^8

    Human Body(M)x10^
    8

    Fe

    .0052

    2230

    Zn

    1720

    Cu

    1650

    PropertiesofZinc

    2+istheonlyaccessibleoxidationstate(d10)
    Bindsbothhardandsoftdonors
    Tetrahedralgeometrypreferred
    56CNareaccessible
    GoodLewisacidbecausehighcharge/radius
    ratio

    10
    Zincisd
    ZincIonis
    colorless
    NotRedox Active

    Hard/SoftAcidBaseTheory
    GoodLewis
    acidbecause
    high
    charge/radius
    ratio

    Borderline
    Metals:
    Fe2+,Ni2+,Zn2+,Co2+,Cu2+
    Ligands:
    SR,his,X,RCO2

    ZincGeometryanddorbitalSplitting
    diagrams.

    RECAP
    WhyZinc:
    1. 2+istheonlyaccessibleoxidationstate(d10)

    Nocomplicationsfromredox activity.

    2.Bindsbothhardandsoftdonors
    3.Tetrahedralgeometrypreferred/56CNare
    accessible

    MedicalApplication:
    TreatGlaucoma
    Carbonicanhydrase
    inhibitorsareapplicable
    duringemergencies
    becausetheyareableto
    rapidlyreducethe
    pressurethathasbuiltup
    insidetheeyeby40%to
    60%.Thelessfluidthatis
    allowedtobuildupyields
    lesspressurebehindthe
    eye.
    http://www.pdb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/pdb49_2.
    html

    Acetazolamide

    Diuretic:Diureticsaredrugsthatincreasetherateofurineflow.
    SoldasthedrugDiamox
    http://jpet.aspetjournals.org/content/115/3/251.abstract

    CarbonicAnhydrase Inhibition

    BadNewsorGoodNews
    Glaucoma:
    Themechanismofactionto
    lowerpressureisnot
    known.Therouteof
    administrationcanbeoral,
    intravenous,topical,or
    inhaledbysmoking,andit
    dictatesmanyofthe
    behavioralandphysiologic
    consequences.Ofthese
    routes,smokinghasthe
    morerapidonsetof
    psychoactiveandother
    pharmacologiceffect

    IsZincBoring?
    http://www.youtube.com/watch?v=99wPiMbk0o

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