
cofactor (biochemistry)

oru protein ithara raasa samyukthamo loha ayono aanu cofactor, athu oru kaattalist enna nilayil oru ensaiminte punk vahikkaan aavasyamaanu (oru raasapravarthanathinte nirakk vardhippikkunna padaarthamaanu kaattalist). biochemical parivarthanangalkku sahayikkunna coffactorukale "helper moleculukal" aayi kanakkakkaam. iva sambhavikkunna nirakkukal ensime kainettiks enna padanamekhalayil savisheshamaan. coffactorukal saadhaaranayaayi ligaandukalil ninnu vyathyasthamaan, avaa palappozhum bandhithamaayi thudarunnathiloode avayude pravartthanam nedunnu.
coffactorukale rund tharangalayi tharamthirikkaam ajaiva ionukalum koensaimukal ennariyappedunna sankeernna jaiva thanmaathrakalum. vitaaminukalil ninnum mattu jaiva avashya poshakangalil ninnum cheria alavil koensaimukal kooduthalum uruthirinjirikkunnu. (chila shaasthranjar ajaiva padaarthangalkku "cofactor" enna padatthinte upayogam parimithappedutthunnu; rund tharangalum ivide ulppeduthiyittundu.)
koensaimukale rund tharangalayi thirichirikkunnu. aadyathethine "prosthettik group" ennu vilikkunnu, athil oru coensime adangiyirikkunnu, athu irukiyirikkunnu (allengil sahavarthithvathode polum) koodaathe oru proteinumaayi sthiramaayi bandhippichirikkunnu. randaamathe tharam koensaimukale "cosbstrateukal" ennu vilikkunnu, avaa proteinumaayi kshanikamaayi bandhappettirikkunnu. cosbstrateukal oru ghattathil proteinil ninnu purathuvarikayum pinneedu rebined cheyyukayum cheyyaam. prosthettik grouppukalkkum kosbstrettukalkkum ore pravarthanamaanu ullathu, ithu ensaimukaludeyum proteinukaludeyum prathikaranam sugamamakkunnu. cofactor illaatha nishkriya ensaimine apoensime ennum cofactor ulla samboornna ensaimine holoensime ennum vilikkunnu. (internaashanal union oof pyoor aandu uplied kemistry (ipac) "koensaimine" alppam vyathyasthamayi nirvachikkunnu, athaayath kuranja tanmatra bharamullah, protein ithara jaiva samyuktham, ayanja reethiyil gadippichirikkunnu, raasa grouppukaludeyo electronukaludeyo verpeduthaavunna carrieraayi ensaimatik prathikaranangalil pankedukkunnu; oro ensaimatik vittuvaravilum punarujjeevippikkappedu oru proteinil karsanamaayi bandhikkappetta, polypeptide ithara unitaayi oru prosthettik groupine nirvachikkunnu.)
chila ensaimukalkko ensime complexukalkko niravadhi coffactorukal aavasyamaanu. udaaharanathinu, glycolysisinteyum citric assid saikilinteyum jangshanile multiensime complexes pairuvettu dehydrajanesinu anchu jaiva coffactorukalum oru loha ayon aavasyamaanu ayanja bandhithamaaya tayamin pyrophosphate (tii. pii. pii), samayabandhithamayi bandhithamaaya lipoamide, flavin adenine daine nucleotide (phaad), cosobstrates nicotinamide adenine daine nucleotide (naad +), coensime eiii (koe), oru loha ayoon (emji 2 +).
jaiva coffactorukal palappozhum vitaaminukalo vitaaminukalil ninnu nirmmichatho aanu. avayil palathilum nucleotide adenosine monophosphate (aambu) avayude gadanakalude bhaagamaayi adangiyittundu, athaayath eiii. tii. pii, coensime eiii, phaad, naad +. eee pothuvaaya ghadana oru purathana rna lokathile ribosymukalude bhaagamaayi oru pothu parinaama uthbhavathe prathifalippichekkaam. thanmaathrayude aambu bhagam orutharam "handle" aayi kanakkaakkaamenn nirddeshikkappettittund, athiloode ensaiminu koensaimine vividha kaattalatik kendrangalkkidayil maattaan kazhiyum.
vargeekaranam.
coffactorukale rund pradhana grouppukalaayi tirikkaam flavin allengil heam polulla jaiva coffactorukal; loha ionukal mg2 +, Cu +, mn2 +, irumbu-sulfur klasttarukal polulla ajaiva coffactorukal.
jaiva coffactorukale chilappol "koensaimukal", "prosthettik grouppukal" enningane veendum vibhajikkunnu. coensime enna padam prathyekamaayi ensaimukale soochippikkunnu, athupole, oru proteente pravarthanaparamaaya gunangale soochippikkunnu. maruvashathu, "prosthettik group" oru cofactorine oru proteinumaayi (irukiyatho samayabandhithamo) bandhippikkunnathinte swabhaavathinu oonnal nalkunnu, athinaal ithu oru gadanaaparamaaya swathine soochippikkunnu. vividha srothassukal koensaimukal, coffactorukal, prosthettik grouppukal ennivayude alppam vyathyasthamaaya nirvachanangal nalkunnu. chilar koensaimukal allah, prostettik grouppukalaayi karsanamaayi bandhippichirikkunna jaiva thanmaathrakale kanakkakkunnu, mattullavar ensaiminte pravarthanatthinu aavashyamaaya ellah protein ithara jaiva thanmathrakaleyum koensaimukalaayi nirvachikkukayum coensime prostettik grouppukalaayi karsanamaayi bandhippichirikkunnave tharamthirikkukayum cheiyunnu. eee padangal palappozhum ayanja reethiyil upayogikkunnu.
biochemistry sciencesile trendukal" ennathil 1980-leeii oru kathil saahithyathile ashayakkuzhappavum prosthettik grouppukalum koensaimukal group thammilulla ekapaksheeyamaaya vyathyasavum rekhappeduthukayum inipparayunna padhathi nirddeshikkukayum cheythu. ivide, coffactorukale ensime pravarthanatthinu aavashyamaaya protein substrate koodaathe oru adhika padaarthamaayum orotta ensime thanmathrayumaayi bandhippichirikkunna muzhuvan kaattalatik saikilinum vidheyamaakunna oru padaarthamaayi oru prosthettik groupaayum nirvachichu. ennirunnaalum, rachayithaavin oru "koensaiminte" ellaam ulkkollunna orotta nirvachanathil ethaan kazhinjilla, eee padam saahithyathile upayogathil ninnu ozhivaakkanamenn nirddeshichu.
ajaiva coffactorukal.
loha ionukal.
loha ionukal saadhaarana kofaaktarukalaanu. eee kofaaktarukalekkurichulla patanam bio oorgaanik kemistry mekhalayilaanu. poshakaahaaratthil, avashya trace gadakangalude pattika coffactorukal enna nilayil avayude punk prathifalippikkunnu. manushyaril eee pattikayil saadhaaranayaayi irumbu, magneeshyam, manganese, cobalt, chembu, sink, molybdinum enniva ulppedunnu. kromiyathinte kuravu glucose sahishnutha kuraykkaan kaaranamaakunnundengilum, eee lohathe oru cofactoraayi upayogikkunna oru manushya ensime thiricharinjittilla. iodine oru avashya trace moolakam koodiyaanu, ennaal eee moolakam oru ensime cofactor ennathilupari thyroid hormonukalude gadanayude bhaagamaayi upayogikkunnu. manushya bhakshanathinte oru gadakamaayi kaalsyam aavasyamulla mattoru prathyeka kesaanu, naitrik ooksaid synthase, protein phoosphettas, adenilate kinace thudangiya niravadhi ensaimukalude poornna pravarthanatthinu ithu aavasyamaanu, ennaal kaalsyam eee ensaimukale alosteric niyanthranatthil sajeevamaakkunnu, palappozhum eee ensaimukalumaayi oru complexil calmodulin bandhippikkunnu. athinaal, kaalsyam oru sell signalling thanmathrayaanu, athu niyanthrikkunna ensaimukalude cofactoraayi saadhaaranayaayi kanakkakkilla.
assotobacter" janussile naitrajan-fixing bacteriayude naitrajanesile vanadium, thermophilic archaean "pyrococcus furiosus" nte aldehyde ferredoxin ooksidooredaktesile tangsttan, samudra dayattamaaya "talasiosira weisfloggy" yill ninnulla carbonic unhydrasile cadmium enniva polulla ensime kofaaktarukalaayi mattu jeevikalkk adhika lohangal aavasyamaanu.
pala kesukalilum, coffactoril ajaiva, jaiva gadakangal ulppedunnu. irumbumaayi ekopippichirikkunna porphyrine valayam adangiyirikkunna heam proteinukalaanu vaividhyamaarnna oru koottam udaaharanagal.
irumbu-sulfur klasttarukal.
irumbu, sulfur aattangalude samuchayangalaan irumbu-sulfur klasttarukal, avaa proteinukalkkullil sisteenail avashishtangalaal pidikkappedunnu. electron transfer, redox sensing, structural moduleukal ennivayulppede gadanaaparavum pravarthanaparavumaaya rolukal avaa vahikkunnu.
oorgaanik.
ensaimumaayi ayanjatho karshanamaayo bandhippichu prathikaranatthil nerittu pankedukkaan kazhiyunna cheria jaiva thanmathrakalaanu (saadhaaranayaayi 1000 dayil thaazheyulla oru tanmatra pindam) jaiva coffactorukal. randaamathe saahacharyathil, ensaimine denature cheyyaathe neekkam cheyyaan prayaasamullappol, athine prosthettik group ennu vilikkam. ayanjathum karsanavumaaya coffactorukal thammil moorchayulla vibhajanam illennu oonnipparayendathu pradhaanamaan. vaasthavathil, naad + polulla palathum chila ensaimukalil urachunilkkukayum mattullavayil ayanjunilkkukayum cheiyunnu. mattoru udaaharanam tayamin pyrophosphate (tii. pii. pii) aanu, ithu transkettoles allengil pairoovettu decarboxylasil karsanamaayi bandhippichirikkunnu, athesamayam pairoovettu dehydrogenesil karsanamaayi bandhippichitla. udaaharanathinu, flavin adenine daine nucleotide (phaad), biotine, lipoamide ennee mattu koensaimukal karsanamaayi bandhippichirikkunnu. irukiya bandhita coffactorukal pothuve, ore prathikarana chakratthil punarujjeevippikkappedu, athesamayam ayanja bandhita coffactorukal mattoru ensime uthejippikkunna thudarnnulla prathikaranatthil punarujjeevippikkaan kazhiyum. randaamathe saahacharyathil, cofactorine oru substrate allengil cosbstrate aayi kanakkakkaam.
vitaaminukalkk niravadhi jaiva gadakangalude (udha.jii.vitaaminukal bii1, bii2, bii6, bii12, niasin, phoolik assid) allengil koensaimukal (udha.jii.vitaamin sii). ennirunnaalum, vitaaminukalkk shareerathil mattu pravarthanangalundu. electron kaariyarukalaya naad, phaad, asail grouppukal vahikkunna coensime eiii enniva polulla niravadhi jaiva coffactorukalil oru nucleotide adangiyirikkunnu. eee coffactorukalil bhooribhaagavum vaividhyamaarnna speesheesukalil kaanapedunnu, chilath ellah tharatthilulla jeevajalangalkkum saarvathrikamaanu. eee vishalamaaya vitharanathinu oru apavaadam eee archaea groupil parimithappedutthiyirikku methanojanukalil parinamicha savisheshamaaya kofaaktarukalude oru koottamaanu.
upapachayam idanilakkaar enna nilayil coffactorukal.
mettabolisatthil niravadhi raasapravarthanangal ulppedunnundengilum mikathum pravartthana grouppukalude kaimaattam ulppedunna chila adisthaana tharatthilulla prathikaranangalkk keezhilaanu. eee saadhaarana rasathanthram koshangale vyathyastha prathikaranagalkkidayil raasa grouppukal vahikkaan oru cheria koottam metaboolik idanilakkaare upayogikkaan anuvadikkunnu. eee group-transfer idanilakkaar ayanja bandhita jaiva kofaaktarukalaanu, palappozhum koensaimukal ennu vilikkunnu.
oro klaas group-transfer prathikaranavum nadathunnathu oru prathyeka cofactoraanu, athu ulppaadippikkunna oru koottam ensaimukalude substrate athu upayogikkunna oru koottam ensaimukalum. nicotinamide adenine daine nucleotide (naad +) oru cofactoraayi upayogikkunna dehydrogenesukalaanu ithinu oru udaaharanam. ivide, noorukanakkinu vyathyastha tharam ensimeukal avayude substrateukalil ninnu electronukale neekkam cheyyukayum naad + neey naad aayi kuraykkukayum cheiyunnu. eee kuranja cofactor appol electronukalkku avayude substrateukal kuraykkaan aavashyamaaya koshatthile eathenkilum reductasukalude substrate.
athinaal, eee coffactorukal mettabolisatthinte bhaagamaayi thudarchayaayi recycle cheiyunnu. udaaharanathinu, manushyashareerathile motham eiii. tii. piyude alavu ekadesham 0.01 molaanu. eee eiii. tii. pii nirantharam eiii. dii. pii aayi vibhajikkappedukayum pinneedu veendum eiii. tii. pii aayi parivartthanam cheyyappedukayum cheiyunnu. athinaal, eathu samayathum, eiii. tii. pii + eiii. dii. piyude motham alavu valare sthiramaayi thudarunnu. manushyakoshangal upayogikkunna oorjjathinu prathidinam 100 muthal 150 moll vare eiii. tii. pii jalavishleshanam aavasyamaanu, athaayath ekadesham 50 muthal 75 kilogram vare. saadhaarana saahacharyangalil, manushyar avarude sareerabhaaram divasathil eiii. tii. pii. aayi vardhippikkunnu. athaayath oro eiii. tii. pii. thanmathra prathidinam 1000 muthal 1500 thavana vare recycle cheyyappedunnu.
parinamam.
ariyappedunna ellah jeevajaalangalilum adangiyittulla eiii. tii. pii, naadh thudangiya jaivaghadakangal upapachayam moolamulla oru pradhana gadakamaanu. atharam saarvathrika samrakshanam soochippikkunnathu eee thanmathrakal jeevajaalangalude vikasanathinte valare neratthe thanne parinamichu ennaanu. athinaal, nilavile chila kofaaktarukalenkilum ekadesham 4 bilyan varshangalkk munbu jeevichirunna avasana saarvathrika poorvvikaril undayirikkaam.
bhoomiyile jeevacharithrathil jaiva coffactorukal munbuthanne undaayirunnirikkam. methyl, asail, phosphoril group transfer, redox prathikaranangal thudangiya niravadhi adisthaana upapachayam prathipravartthanangale uthejippikkunna coffactorukalil nucleotide adenosine adangiyirikkunnu. athinaal, sarvvyaapiyaaya eee raasa charutha aarr. enn. eiii lokathinte avashishtamaayi nirddeshikkappettittund, aadyakaala ribosymeukal niyantrithamaaya oru koottam nucleodideukaleyum anubandha samyukthangaleyum bandhippikkunnathin parinamichu. adenosine adisthaanamaakkiyulla coffactorukal parasparam maattaavunna adapterukalaayi pravarthichathaayi karuthappedunnu, ithu ensaimukale anuvadikkukayum ribosymukale puthiya coffactorukale bandhippikkaan anuvadikkukayum cheiyunnu, nilavilulla adenosine-binding domainukalile cheria parishkkaranangaliloode, yadhaarthathil vyathyastha cofactorine bandhippikkunnathinaayi parinamichu. oru puthiya upayogathinaayi munkootty vikasippicha ghadanaye poruthappeduthunnathinu eee prakriya "eksaapteshan" ennu vilikkunnu.
candida boydini sailos reductasinte cofactor specificialitye nadfill ninnu nadfilake pareekshanaathmakamaayi maattiya mutationukal aduthide pravachicha oru computational reethiyaanu, ipro.
charithram.
1906 ll arther harden vilyam yangum chernnu thiricharinja naad + aayirunnu aadyathe jaiva cofactor. vevichathum filter cheythathumaaya yeest sathil cherkkunnath thilappikkaatha yeest sathil alcoholic pulippikkal valareyadhikam thwarithappeduthunnathaayi avar shradhichu. eee phalathinu utharavaadikalaaya thirichariyappedaatha gadakathe avar "cofferment" ennu vilichu. yeest sathil ninnulla dairkhyameriyathum budhimuttullathumaaya shudheekaranathiloode, eee taapa-sthirathayulla gadakathe hans voonn euler-shelpin nucleotide panchasaara fosfettaayi thiricharinju. irupathaam noottaandinte thudakkathil udaneelam mattu coffactorukal thiricharinju, 1929 ll kaal lohmann eiii. tii. pii. yeei verthirichu, 1945 ll fritts albert lipman coensime eiii kandethi.
eee thanmaathrakalude pravartthanangal aadyam nigoodamaayirunnu, ennaal 1936-ll oottoo heinrich warberg hydride kaimaattatthil naad +-nte pravartthanam thiricharinju. eee kandethalinethudarnnu 1940-kalude thudakkathil panchasaarayude ooksideshanum eiii. tii. pii. yude ulppaadanavum thammilulla bandham sthaapicha herman kalkkarinte pravarthanamaanu nadannathu. 1941ll fritts albert lipman nirddeshicha oorjja kaimaattatthil eiii. tii. piyude kendra punk ithu sthireekarichu. pinneedu 1949ll morris friedkinum albert ell. citric assid saikkil, eiii. tii. pii. yude samanvayangal thudangiya upapachayam vazhikale naad + bandhippikkunnuvennu lehinger theliyichu.
proteinil ninnu uruthirinja coffactorukal.
niravadhi ensaimukalil, protein shreniyude oru bhagam vivarthanaananthara parishkkaranatthiloodeyaanu cofactoraayi pravartthikkunna bhagam roopappedunnathu. ithu palappozhum protein pravarthanatthinaayi loha ayoon polulla oru baahya binding gadakathinte aavasyakathaye maattisthaapikkunnu. sugandha avashishtangalude ookseekaranam, avashishtangalkkidayil bandhippikkal, pilarpp allengil valaya roopeekaranam enniva saadhyamaaya parishkkaranangalaakam. amino aasidukal saadhaaranayaayi puthiya pravartthanangal nedunnathil phosphorylation, methylation allengil glycosylation polulla mattu poost-translation protein parishkkaranangalil ninnu eee mattangal vyathyasthamaan. ithu proteininte pravartthanam vardhippikkunnu; parishkkarikkappedaathu amino aasidukal saadhaaranayaayi assid-bays prathikaranangalil parimithappedutthiyirikku, koodaathe livsinte maattam protein electrophilic sittukal allengil free raadikkalukale sthirappeduthaanulla kazhivu nalkum. cofactor ulppaadanathinte udaaharanangalil rund tryptophan side cheyinukalil ninnu uruthirinja tryptophan tryptophilkvinan (tii. tii. kyu), alaa-serr-gly motifil ninnu uruthirinja 4-methylidene-imidasol-5-vann (meoo) enniva ulppedunnu. ex-reey chrystallography maas spectroscopy upayogichaanu proteinil ninnu uruthirinja kofaaktarukalude swabhaavasavisheshatha nadathunnathu; krameekaranam mattappetta saittukale eluppathil thirichariyaathathinaal gadanaaparamaaya daatta aavasyamaanu.
noonn-ensaimatik coffactorukal.
protein sajeevamaakkukayo thadayukayo pravartthikkaan aavasyamullatho aaya protein ithara (allengil protein) thanmaathrakale kooduthal vishaalamaayi soochippikkaan jeevashaasthrathinte mattu mekhalakalil eee padam upayogikkunnu. udaaharanathinu, risapttar proteinukalumaayi bandhippikkukayum sajeevamaakkukayum cheiyunna hormonukal polulla ligaandukale coffactorukal allengil qoo aaktivettarukal ennu vilikkunnu, athesamayam risapttar proteinukale thadayunna thanmaathrakale corpressorukal ennu vilikkunnu. censory neuronukalil pathivayi kaanapedunna resepterukalude jii protein-cuppled risapttar kudumbamaanu atharamoru udaaharanam. resepterukalumaayulla ligand binding jii proteine sajeevamaakkunnu, athu pinneedu ifakttar sajeevamaakkunnathin oru ensaimine sajeevamaakkunnu. ashayakkuzhappam ozhivakkaan, ligand-binding mediated aaktiveshan allengil adichamarthal ulla atharam proteinukale korgulettarukal ennu vilikkanamennu nirddeshikkappettittund.

