COBALT ENZYMES AND THEIR IMPORTANCE IN THE BIOLOGICAL systems

INTRODUCTION TO THE METAL COBALT

Cobaltisoneofthefirsttransitionmetalseries. Stableformofcobaltiscreatedinsupernovasbyther process. Itcomprises0.0029%oftheEarth'scrust Cobaltoccursincopperandnickelmineralsandin combinationwithsulfurandarsenicinthesulfidiccobaltite (CoAsS),safflorite(CoAs2)andskutterudite(CoAs3) minerals. Cobaltisnotfoundasanativemetal. Itsmainoresarecobaltite,erythrite,glaucodotand skutterudite.

COBALT AS AN ENZYME.??
Somemetalsdirectlyexistasenzymesandinsomecasesthese setofenzymesrequireacoenzymeoracofactorfortheiractivity coenzymedependent. Theenzymebecomesfunctionalonlywhenthecoenzymebindsto them. Thecobaltispresentasalinkageinthecorrinringinthese coenzymeandactsasanenzyme,hencecalledascobaltenzyme. Example:B12 (withcorrinring) Thereareseveralenzymescontainingcobaltinaformotherthan thatinthecorrinringofvitaminB12.

COBALAMINE-

VITAMIN B12

(COENZYME -COBALT COMPLEX )

Watersolublevitaminwithakeyroleinthenormalfunctioningofthe brainandnervoussystem,andfortheformationofblood. Itcontainsthebiochemicallyrareelementcobalt. Thecobalaminbasedproteinsusecorrintoholdthecobalt. B12 existswithtwotypesofalkylligand:methylandadenosyl. MeB12 promotesmethyl(CH3)grouptransfers. TheadenosylversionofB12 catalyzesrearrangementsinwhicha hydrogenatomisdirectlytransferredbetweentwoadjacentatomswith concomitantexchangeofthesecondsubstituent,X,whichmaybeacarbon atomwithsubstituents,anoxygenatomofanalcohol,oranamine.

VitaminB12 anditscoenzymeformsareprominentcobaltcontaining cofactors. Theyarepartofthelargerclassofthenaturaltetrapyrrolicmetal complexes. Ithasagroupofcobaltcontainingvitamercompoundswhichinclude: cyanocobalamin(anartifactformedfromusingactivatedcharcoal, whichalwayscontainstracecyanide,topurifyhydroxycobalamin) hydroxocobalamin(anothermedicinalform,producedbybacteria) thetwonaturallyoccurringcofactorformsofB12 :adenosylcobalamin andmethylcobalamin. B12 isthemostchemicallycomplexofallthevitamins. ThestructureofB12 isbasedonacorrinring.

STRUCTURE
ItisaCOENZYMECOBALTCOMPLEXwherethemetalion issituatedatthecentreofthemacrocyclicplanarringcompound of4(four)pyrrolederivatives. Cobaltmetalionisdirectlybondedtothe5 carbonatomof thedeoxyribosemoiety.

Thisfurherbondedtoadenine.

Ontheothersideofthering,cobaltisattachedtothe dimethylbenzimidazolebase.

Thisinturnislinkedtothesidechainofapyrrolering throughriboseandphosphatemoieties.

COBALAMINE

Formula:C63 H88 CoN14 O14 P Mol.Mass:1355.37g/mol Colinkedto5deoxyadenosyl AgainCoattachedtodimethyl benzimidazolebase. Inturnlinkedtosidechainof pyrrole ringthroughriboseandphosphate moieties.

qTherearevariousformsofthecobalamin(socalledduetothe presenceofcobalt)molecule. qSomeoftheseare;methyl,cyano,adenosyland hydroxocobalamin(B12b). qTherearealsonitrite(B12c),sulphitoandaquacobalamins.

qMostoftheB12presentinanimaltissuesisinoneofthetwo coenzymeforms,adnosylcobalaminormethylcobalamin,andnot actualvitaminB12(cobalamin),whichmaybepresentdueto diffusionfromgutbacteriaoractivetransportusingintrinsic factor. q qCobalamincoenzymesarepartoftheprostheticgroup,thatis thetightlyboundgroupofcoenzymes.

MAINSOURCES COBALTENZYMES.

NON - CORRINOID FORMS .

Cobaltalsoexistsasenzymeinnoncorrinoidforms..!! Noncorrincobaltisreceivingincreasedinterestnotonlyin bioinorganicchemistrybutalsoinbiotechnology. Itsavailabilityandremarkablechemicalversatilitymakescobaltan invaluablecatalystinthechemicalindustry. Eightnoncorrincobaltcontainingenzymeshavebeenisolated.

Methionineaminopeptidase,Prolidase,Nitrilehydratase,glucoseisomer MethylmalonylCoAcarboxytransferase,Aldehydedecarbonylase, lysine2,3aminomutase,andbromoperoxidase.

Knowncobaltcontainingenzymes(noncorrinoid) Enzyme or protein

Methionine amino peptidase Prolidase Nitrile hydratase Glucose isomerase Cobalt transporter

Source
Animals, yeast, bacteria Archae Actinomycetes and bacteria Actinomycetes Actinomycetes and yeast

Cofactor content
2 Co per subunit 12 Co per subunit 1 Co in each -subunit 1 Co per 4 subunits

Postulated role for cobalt

Hydrolysis Hydrolysis H2O activation, CNtriple-bond hydration and Isomerization protein folding Cobalt uptake Carboxytransferation Decarbonylation for Aldehyde Mutation

Methylmalonyl-CoA Bacteria carboxytransferase Aldehyde decarbonylase Algae Lysine-2,3aminomutase Bromoperoxidase Cobalt-porphyrincontaining protein Bacteria Bacteria Bacteria

1 Co, 1 Zn per subunit 1 Co- porphyrin per subunit 0.51 Co per subunit

0.35 Co per 2 subunits Bromination 1 Co-porphyrin per protein Electron carrier

cobalamin plays a number of crucial roles in many biological functions .

Biochemicalprocessmusthappenwhereverandwheneverthey arerequired. Enzymescanoccurinbiologicalfluidsassolublematerialsoras boundentitiestothemembraneorcouldbeevenpartofahuge enzymecomplex. Thesearetheproteinswhosebackboneismadeupofachainof peptidelinkedaminoacidswithavarietyofstructures. Cobaltislessfrequentlyencounteredinmetalloenzymesbut neverthelessanimportantcofactorinvitaminB12 dependent enzymes.

 Itisusedasaconcentratedsourceofradiationincancer therapyandfoodsterilization,andasaradioactivetracerin biologicalandindustrialapplications. Ithasalsoservedasaspectroscopicprobeinmetalloenzymes. Substitutingcobaltforzinchasoftenbeenausefultoolto investigatethestructuralbasisofcatalyticpropertiesinzinc enzymes. B12 isnormallyinvolvedinthemetabolismofeverycellofthebody, especiallyaffectingtheDNAsynthesisandregulationbutalsofatty acidsynthesisandenergyproduction.

CoenzymeB12 'sreactiveCCobondparticipatesinthreemain typesofenzymecatalyzedreactions.Theyareasfollows: Isomerases:Rearrangementsinwhichahydrogenatomis directlytransferredbetweentwoadjacentatomswith concomitantexchangeofthesecondsubstituent,X,whichmay beacarbonatomwithsubstituents,anoxygenatomofan alcohol,oranamine. Methyltransferases:Methyl(CH3)grouptransfers betweentwomolecules. Dehalogenases:Reactionsinwhichahalogenatomis removedfromanorganicmolecule.Enzymesinthisclasshave notbeenidentifiedinhumans.

Conclusion:
Although metal ions play a variety of roles in natural proteins, including nucleophilic catalysis, electron transfer, and the stabilization of protein structure, the functions of cobalt have rarely been studied. Cobalt is used in a limited number of enzymes, unlike iron and zinc.

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