
entopeptidase

 
manushyarilum mattu mrugangalilum dahanathil earppettirikkunna duvodeenathile koshangal ulppaadippikkunna oru ensaimaanu enteropeptidase (entarokinesu ennum ariyappedunnu). enteropeptidase trypsinogene (oru saimojan) athinte sajeeva roopamaaya trypsinilekku parivartthanam cheiyunnu, athinte falamaayi pancreatic digestive ensimeukal thudarnnu sajeevamaakunnu. enteropeptidasinte abhavam kudal dahana vaikalyathin kaaranamaakunnu.
kudal brush boarder membranile entarokinesine nankooramidunna 82-140 kda-yude disulfide-linked hevi-cheyin, kaattalitik subunit adangiya 35-62 kda-yude laitt-cheyin enniva ulkkollunna oru serin protees aanu enteropeptidase. serin proteesukalude chemotrypsin vamshathinte bhagamaaya enteropeptidase gadanaaparamaayi eee proteinukalumaayi saamyamullathaan.
charitraparamaaya praadhaanyam.
dahananaala shareerashaasthrathekkurishullachu padanatthinu 1904 leeii physiology allengil medisin nobel sammanam labhicha ivaan pavlov aanu entopeptidase kandethiyathu. mattu ensaimukale sajeevamaakkunna aadyathe ensaimaanu ithu, upapachayam niyanthrikkunnathin serin proteasukal engane roopakalppana cheythirikkunnu ennathinte sradheyamaaya udaaharanamaayi ithu thudarunnu. kudalinullile sakthamaaya pravartthanavumaayi thaarathamyappeduthumbol pancreasil dahana ensaimukalude nishkriya pravartthanam ariyaamaayirunnuvenkilum eee vyathyaasathinte adisthaanam anjjaathamaayirunnu. 1899-ll paavlovinte vidyaarthi enn. pii. skipovalnikov, cannin duvodenal sravangal pancreatic ensaimukalude, prathyekichu trypsinogen ennivayude dahana pravartthanatthe naadakeeyamaayi uthejippikkunnuvennu theliyichu. mattu ensaimukale sajeevamakkaan kazhiyunna kudalile oru prathyeka ensaimaayi sajeevamaaya thathwam amgeekarikkappettu. pavlov ithinu enterokinaas ennu perittu. entokinesu oru cofactoraano ensaimaano enna charcha pariharichathu kunitts aanu, entokinesu vazhi trypsinogen sajeevamaakkunnath kaattalatik aanennu addeham kaanichu. 1950kalil, oru enn-terminal hexapeptidinte pilarpp vazhi kannukaali trypsinogen autocataliticaayi sajeevamaanenn kaanichu. kooduthal krithyamaaya iubmb naamamaya enteropeptidase 1970 muthal nilavilundu. ennirunnaalum, 'entarokinesu' enna yadhaartha perinu oru neenda charithramund, athu ippozhum saadhaarana upayogathilaanu.
ensaiminte ghadana.
deuvodenalinteyum jejunal mucosayudeyum brush borderil praadeshikavalkkarikkum oru saimojan, proenteropeptidase aayi samanvayippikkukayum cheiyunna type II transmembran serin protees (ttsp) aanu enteropeptidase, ithinu duvodenase allengil tripsin upayogichu sajeevamaakkal aavasyamaanu. vyathyastha neelamulla enn-terminal propeptide seekwansukalulla single cheyin saimojan aayi ttsps samanvayippikkunnu. valare samrakshikkappetta aaktiveshan motifil adangiyirikkunna lysine allengil arjinin avashishtangalude carboxyl vashath villaliloode eee ensimeukal sajeevamaakunnu. sajeevamaakkikkazhinjaal, proo-kaattalatik domainukale bandhippikkunna oru samrakshitha disulfide bondiloode ttsps membran-boundu aayi thudarumennu pravachikkappedunnu.
kannukaalikalude enteropeptidesinte kaaryatthil praadhamika vivarthana uthppannathil 1035 avashishtangal adangiyirikkunnu, prathekshikkunna pindam 114.9kda aanu. ekadesham 160kda enna vyakthamaaya pindam 30-40% enna nirddishta carbohydrate ulladakkavumaayi poruthappedunnu, thulya alavil neutral, amino panjasaarakal undu. lysa800 nuu sheshamulla aaktiveshan kleevej saitt pakwathayulla kannukaalikalude enteropeptidesinte bhaarameriyathum bharam kuranjathumaaya shringalakale vibhajikkunnu. hevi cheyin (Heavy Chain) ll 17 saadhyathayulla enn-linked glycosylation saittukalum laitt cheyin (Light Chain) ll moonnu saittukalum undu; ivayil bhooribhaagavum mattu speesheesukalil samrakshikkappedunnu. 
transmembran aankarine pinthunaykkunna enn-terminasinu sameepam kanatha shringalaykku oru hydrophobic vibhaagamund. kanatha shringhala enteropeptidesinte prathyekathaye swaadheenikkunnu. native enteropeptidase soyabean tripsin inhibittarine prathirodhikkunnu. ennirunnaalum, swaabhaavika protein parimithamayi kurachaalum allengil koos koshangalile mutagenesis, expression ennivayaalum thayyaaraakkappedunna otappetta prakasha shringhala sookshumamaanu. native enteropeptidasinum otappetta laitt cheyinum gly-(eiii. ezz. pii) 4-lies-nappinode samanamaaya pravartthanamundu, ennaal otappetta laitt cheyin trypsinogen ennathilekkulla pravartthanam vyakthamaayi kurachittundu. trypsinogen thirichariyunnathile oru samana selective takaraar rund-cheyin enteropeptidasil choodaakkunnathiloodeyo asattaileshaniloodeyo utppaadippikkaan kazhiyum. eee swabhaavam soochippikkunnathu trypsinogen opttimal thirichariyaan kaattalatik sentarum onno athiladhikamo secondary substrate-binding saittukalum anivaaryamaan ennaanu.
pravartthanam.
badal peru (entokinesu) undaayirunnittum, proteinukalile pepttaid bondukalude jalavishleshanathe uthejippikkukayum mattu kainaasukalil ninnu vyathyasthamayi phoosphett grouppukalude kaimaattatthe uthejippikkaathirikkum cheiyunna oru serin proteasaanu enteropeptidase. enteropeptidase tripsin polulla pravartthanam prakadippikkunnu, oru prathyeka pilarpp saittil (asp-asp-asp-lies) oru lysine pinthudarunna proteinukal pilarunnu. eee villal kudalinte lumenile chemotrypsinogen, prolaastes, procarboxypeptidae, prolipace thudangiya mattu pancreatic saimojankalude swathanthramaaya sajeevamaakkalin kaaranamaakunnu. tripsinojante proo-reejiyanil eee kramam adangiyirikkunnathinaal, enteropeptidase athinte "inn vivo" sajeevamaakkal uthejippikkunnu
trypsinogen → tripsin + proo-reejian (wall-asp-asp-asp-lies)
janithakavum rogathinte prasakthiyum.
manushyaril, chromosome 21q21-ll tii. emm. pii. aarr. ezz. ezz. 15 jeane ("entku" ennum munbu "press 7" ennum ariyappettirunnu) encode cheythathaanu enteropeptidase. eee jeenile chila asambandhavum frameshift mutationukalum enteropeptidesinte kuravu kaaranam baadhicha sisukkalil thazhachuvalarunnathil gurutharamaaya paraajayatthinte savisheshathayulla apoorvamaaya oru resessive disorderilekku nayikkunnu. entopeptidase marnah expression proximal cherukudalil parimithappedutthiyirikku, koodaathe protein deuvodenathinteyum proximal jejunathinteyum entarosaittukalil kaanapedunnu. pancreasil ninnu duvodenamilekku sravikkumbol, trypsinogen enteropeptidasine neridukayum sajeevamaakkukayum cheiyunnu. tripsin pinneedu mattu pancreatic serin protees saimojans (chemotrypsinogen, prolaastes), metalloprotes saimojans (procarboxypeptidae), prolipace enniva vibhajikkukayum sajeevamaakkukayum cheiyunnu. eee lalithamaaya rund ghatta cascade vazhi, eee dahana hydrolesukalude vinashakaramaaya pravartthanam kudalile lumenil parimithappedutthiyirikku. enteropeptidasinte janmana undaakunna kuravu moolamundaakunna kudal malabsurption eee paathayude shaareerika praadhaanyam prakadamaakkunnu. eee avastha jeevanu bheeshaniyaakaamenkilum pancreatic sathinte vaakkalulla supplementationode prathikarikkunnu.
aaplikkeshanukal.
enteropeptidesinte prathyekatha ithine biochemical aaplikkeshanukalil oru anuyojyamaaya upakaranamaakkunnu; eee shreniyil bandhippichirikkunna sii-terminal affinity tagg (poolii-hiss polullava) adangiya oru fusion proteine protein shudheekaranathethudarnnu taargett protein labhikkunnathin enteropeptidase upayogichu pilartthaam. neremarichu, sajeevamaakkunnathin munbu pilarenda proteesukalude enn-terminal proo-sequence enteropeptidase upayogichu sajeevamaakkunnathin parivartthanam cheyyaan kazhiyum.

