
ootak transglutaminase

ootak transglutaminase (tii. tii. jee. yaa tii. jee. 2 key roop mein sankshipt) protein-glutamine γ-glutamiletransferess parivaar (yaa buss transglutaminase parivaar) kaa ack 78-key. dee. aeye., calcium-nirbhar enzyme () haye. anya transglutaminas kii tarah, yeh ack lycine avashesh key ack ε-emino samooh aur glutamine avashesh key ack γ-carboxamide samooh key beach protein koo cross-link kartaa haye, ack antar-yaa intramolicular bonned banaata haye joe proteolysis (protein ksharan) key liye atyadhik pratirodhi haye. apane cross-linking kaary key alawa, tii. tii. jee. dee-dimedation, jee. tii. pee.-binding/hydrolysing aur isopeptidase gatividhiyon sahit anya prakaar kii pratikriyaon koo utprerit kartaa haye. transglutaminase parivaar key anya sadasyon key vipareet, tii. tii. jee. vibhinn prakaar key ootakon key antahkoshikiya aur baahyakoshikiya sthaan donon mein paaya jaa sakata haye aur hriday, yakrit aur chhoti aant sahit kaee alag-alag angon mein paaya jaataa haye. antahkoshikiya tii. tii. jee. cytosol mein prachur matra mein hotaa haye lekin naabhik aur mitochondria mein bhee cumm matra mein paaya jaa sakata haye. antahkoshikiya tii. tii. jee. koo apoptosis mein ack mahatvapurna bhoomika nibhaane key liye socha jaataa haye. baahya koshikiya sthaan mein, tii. tii. jee. baahya koshikiya matricks (ee. see. aim.) key protein seey judataa haye, vishesh roop seey fibronectin seey kaskar judataa haye. baahya koshikiya tii. tii. jee. koo koshika asanjan, acm sthirikaran, ghaav upchaar, receptor signalling, koshikiya prasaar aur koshikiya gatishilata seey jodaa gayaa haye.
tii. tii. jee. celiac roga mein autoentigen haye, ack aajivan bimari jisamen aahar gluten kaa sevan ack rogjanak pratiraksha pratikriya kaa kaaran banata haye jisake parinamswarup chhoti aant kii soojan aur baad mein vilas atrophy hoti haye. yeh kaee anya beemariyon key pathophysiology mein bhee shamil kiya gayaa haye, jisamen kaee alag-alag cancer aur neurogenerative roga shamil hain.
sanrachana.
jeane.
maanav tii. tii. jee. jeane 20vein gunasutra (20q11.2-q12) parr sthit haye.
protein.
tii. jee. 2 ack bahu-karyatmak enzyme haye joe transglutaminess seey sambandhit haye joe apsilon-(gaama-glutamile) lycine isopeptide bonned dwara protein key cross linking koo utprerit kartaa haye. anya transglutaminess key samaan, tii. tii. jee. mein ack jee. tii. pee./jee. dee. pee. binding site, ack utprerak kshetra, dou beeta bairal aur ack beeta-sandwich hotaa haye. baadhya jee. dee. pee., jee. tii. pee., yaa aeye. tii. pee. key saath tii. jee. 2 kii chrystal sanrachanaon ney pradarshit kiya haye kii tii. jee. 2 key inn roopon mein ack "bund" sanrachana koo apanaaya jaataa haye, jabaki ack avarodhak gluten peptide nakal yaa anya samaan avrodhakon dwara kabja kiye gaye sakriya sthal key saath tii. jee. 2 ack "khule" sanrachana koo apanaata haye. khule sanrachana mein tii. jee. 2 key chaar domen ack vistaarit vinyas mein vyavasthit kiye jaate hain, jisase utprerak gatividhi kii anumati milati haye, jabaki bund sanrachana mein dou see-terminal domen utprerak core domen parr mudey hotey hain jisamen avashesh see. aaee. aiss.-277 shamil hotaa haye. aine-terminal domen kewal dou alag-alag anuroopataon key beach mamuli sanrachanaatmak parivartan dikhaata haye.
tantra.
maanav tii. tii. jee. mein crosslinking key liye utprerak tantra mein tii. tii. jee. key sakriya sthal mein ack see. aaee. aiss. avashesh seey thayol samooh shamil hotaa haye. thayol samooh protein yaa peptide substrate kii satah parr glutamine avashesh key carboxamide parr hamla kartaa haye, amonia chhodata haye, aur ack theoester madhyavarti kaa utpaadan kartaa haye. theoester madhyavarti parr phir dusare substrate (aamtaur parr ack lycine avashesh seey) kii satah amine dwara hamla kiya jaa sakata haye. pratikriya kaa antim utpaad dou substrate (i.) key beach ack sthir isopeptide bandhan haye.ee. cross linking). vaikalpik roop seey, theoester madhyavarti koo hydrolyse kiya jaa sakata haye, jisake parinamswarup glutamine avashesh kaa glutamic acid (i.ee. demedation). tii. tii. jee. dwara utprerit glutamine avasheshon key nirjalikaran koo celiac roga mein gluten key liye rogjanak pratiraksha pratikriya seey jodaa gayaa haye. cross linking aur demidation pratikriyaon key liye ack yojnabaddh chitra 1 mein pradaan kiya gayaa haye.
viniyaman.
tii. tii. jee. kii abhivyakti jatil sanket cascades key aadhar parr pratilekhan star parr viniyamit kii jaati haye. ack baar sanshleshit honey key baad, adhikansh protein koshika dravya, plasma jhilli aur acm mein paaya jaataa haye, lekin ack chhota saa ansh naabhik mein sthanantarit hotaa haye, jahaan yeh pratilekhan karakon key viniyaman key madhyam seey apani abhivyakti key niyantran mein bhaag letaa haye.
tii. tii. jee. dwara cross-linking gatividhi key liye see. aeye. 2 + ayanon key bandhan kii aavashyakta hoti haye. kaee see. aeye. 2 + ack ekal tii. tii. jee. anu seey juda sakate hain. vishesh roop seey, tii. tii. jee. 5 alag-alag bandhan sthalon parr 6 calcium ayanon taka baandhata haye. inn bandhan sthalon mein utparivartan seey calcium kaa sambandh cumm hotaa haye, jisase enzyme kii transglutaminase gatividhi cumm hoe jaati haye. isake vipareet, jee. tii. pee. yaa jee. dee. pee. key ack anu kaa bandhan enzyme kii paraspar jodane kii gatividhi koo rokta haye. isaliye, jee. tii. pee./jee. dee. pee. kii apekshaakrit uchch sandrata aur koshika key ander calcium key nimn star key kaaran antahkoshikiya tii. tii. jee. jyaadaatar nishkriya haye. halanki extracellular tii. tii. jee. key gwanine nucleotide kii cumm sandrata aur extracellular space mein calcium key uchch star key kaaran sakriya honey kii ummeed haye, sabooton seey pataa chalaa haye kii extracellular tii. tii. jee. jyaadaatar nishkriya haye. haal key adhyayanon seey pataa chalata haye kii dou visinal cysteine avasheshon, arthaat see. aaee. aiss. 370 aur see. aaee. aiss. 371 key beach ack diasulphide bandhan key gathan seey extracellular tii. tii. jee. koo nishkriya rakhaa jaataa haye. jaba yeh diasulphide bandhan banata haye, tou enzyme ack khuli pushti mein rahata haye lekin utprerak roop seey nishkriya hoe jaataa haye. diasulphide bandhan kaa okseekaran/kamee tii. tii. jee. key sakriyan key liye ack teesare allosteric niyaamak tantra (jee. tii. pee./jee. dee. pee. aur see. aeye. 2 + key saath) key roop mein kaary kartaa haye. thyrodoxin-1 koo diasulphide bandhan koo cumm karke baahya koshikiya tii. tii. jee. koo sakriya karane key liye dikhaaya gayaa haye. ack aur displied bandhan tii. tii. jee. mein, avasheshon see. aaee. aiss.-230 aur see. aaee. aiss.-370 key beach bunn sakata haye. jabaki yeh bandhan enzyme kii mool sthiti mein maujood naheen haye, yeh taba dikhaai detaa haye jaba enzyme okseekaran key madhyam seey nishkriya hoe jaataa haye. calcium kii upasthiti donon diasulphide bandhanon key gathan seey bachaati haye, iss prakaar enzyme okseekaran key liye adhik pratirodhi bunn jaataa haye.
haal key adhyayanon ney sujhaav diyaa haye kii interferon-jee chhoti aant mein extracellular tii. tii. jee. key sakriyak key roop mein kaam curr sakata haye; inn adhyayanon kaa celiac roga key rogjanan parr seedha prabhaav padata haye. tii. tii. jee. key sakriyan koo badey anuroop parivartanon key saath dikhaaya gayaa haye, joe ack compact (nishkriya) seey ack vistaarit (sakriya) anuroopan mein badal jaate hain. (chitra 3 dekhein)
baahyakoshikiya matricks mein, tii. jee. 2 "bund" kiya jaataa haye, mukhya roop seey endoplasmic reticulum protein 57 (aeye. aar. pee. 57) kii okseekaran gatividhi key kaaran. iss prakaar, tii. tii. jee. koo dou alag-alag protein, aeye. aar. pee. 57 aur tii. aar. aiks.-1 dwara allosteric roop seey viniyamit kiya jaataa haye. (chitra 4 dekhein).
kaary.
tii. tii. jee. koo sarvavyaapi roop seey vyakt kiya jaataa haye aur yeh vibhinn cellular dibbon mein maujood hotaa haye, jaise kii cytosol, naabhik aur plasma jhilli. ise pargaman gatividhi key liye ack saha-kaarak key roop mein calcium kii aavashyakta hoti haye. pratilekhan retinoic acid dwara badhaaya jaataa haye. isake kaee kathit karyon mein, yeh ghaav bharane, apoptosis, aur extracellular matricks vikas key saath-saath vibhedan aur koshika asanjan mein ack bhoomika nibhaata prateet hotaa haye. yeh nott kiya gayaa haye kii vibhinn prakaar kii koshikaon mein tii. tii. jee. kii bahut alag gatividhi hoe sakati haye. udaaharan key liye, neurons mein, tii. tii. jee. chot key adheen koshikaon key astitva kaa samarthan kartaa haye jabaki astrocytes mein tii. tii. jee. key liye jeane abhivyakti koo baahar nikaalana koshika astitva key liye fayademand haye.
maanaa jaataa haye kii tii. tii. jee. myosine, actin aur spectrin sahit vibhinn cytoskeletal proteins koo cross-linking karke cytoskeleton key viniyaman mein shamil haye. sakshya seey pataa chalata haye kii antahkoshikiya tii. tii. jee. swayam koo myosine seey jodata haye. yeh bhee maanaa jaataa haye kii tii. tii. jee. koshika-koshika key ghatakon koo bahulak banaakar apoptosis key dauran marti koshikaon kii sanrachana koo sthir curr sakata haye, isaliye koshika-bahulya sthaan mein koshika samagri key risaav koo rokta haye.
tii. tii. jee. mein jee. tii. pee. aiss. gatividhi bhee hoti haih jee. tii. pee. kii upasthiti mein, yeh sanket prakriyaon mein bhaag lene vaale jee. protein key roop mein kaary karane kaa sujhaav detaa haye. isaki transglutaminase gatividhi key alawa, tii. tii. jee. koo kinnez, aur protein diasulphide isomerase, aur demedays key roop mein bhee kaary karane kaa prastaav haye. yeh baad kii gatividhi gliadine peptides key demidation mein mahatvapurna haye, iss prakaar celiac roga key pathology mein mahatvapurna bhoomika nibhaati haye.
tii. tii. jee. pee. dee. aaee. (protein diasulphide isomerase) gatividhi bhee prastut kartaa haye. apani pee. dee. aaee. gatividhi key aadhar parr, tii. tii. jee. proteostasis key viniyaman mein ack mahatvapurna bhoomika nibhaata haye, aich. aiss. aff. 1 (heat shock factor 1) key trimmerisation koo utprerit karke aur iss prakaar garmi key sadame key liye shareer kii pratikriya. tii. tii. jee. kii anupasthiti mein, garmi key jhatake kii pratikriya baadhit hoti haye kyonki aavashyak trimmer naheen banata haye.
naidaanik mahatva.
tii. tii. jee. sabse vyaapak roop seey adhyayan kiya gayaa transglutaminase haye aur kaee beemariyon seey judaa huaa haye. haalaanki, inmein seey koee bhee bimari enzyme kii kamee seey sambandhit naheen haye. vaastav mein, abb taka kissy bhee bimari kaa kaaran tii. tii. jee. gatividhi kii kamee naheen haye aur yeh tii. tii. jee. nockout choohon key adhyayan key madhyam seey pramaanit kiya gayaa haye.
celiac roga.
tii. tii. jee. celiac roga key saath apane sambandh key liye sabse achchha jaanaa jaataa haye. yeh pahali baar 1997 mein celiac roga seey judaa thaa jaba enzyme koo celiac key liye vishisht antibody dwara pehchaane gaye antigen key roop mein paaya gayaa thaa. anty-transglutaminase antibody key parinamswarup gluten samvedansheelta kaa ack roop hotaa haye jisamen "tritis" gluten key liye ack cellular pratikriya joe tii. tii. jee. seey cross-linked hoti haye, transglutaminase vishisht bee-cell pratikriyaon koo uttejit karane mein saksham hoti haye jisake parinamswarup antatah anty-transglutaminase antibody iga aur igg kaa utpaadan hotaa haye. tii. tii. jee. vishesh roop seey glutamine avasheshon koo demidate kartaa haye joe epitope banaata haye joe tii koshikaon koo prastut karane vaale antigen key liye gluten peptide key bandhan sambandh koo badhaata haye, jisase ack anukuli pratiraksha pratikriya shuru hoti haye.
cancer.
haal key adhyayanon seey pataa chalata haye kii tii. tii. jee. soojan aur tumour jeev vigyaan mein bhee bhoomika nibhaata haye. tii. tii. jee. abhivyakti kaee prakaar key cancer koshikaon mein badhee hui haye aur messenkimal sankraman aur stame cell jaise gunon koo badhaava dene kii kshamata key kaaran dawa pratirodh aur metastasis mein funce gaee haye. apane jee. tii. pee. baadhya roop mein, tii. tii. jee. cancer koshika key astitva mein yogdan detaa haye aur ack cancer chaalak prateet hotaa haye. tii. tii. jee. cancer koshikaon aur kaee prakaar key cancer key ootakon mein viniyamit haye, jisamen leukemia, stun cancer, prostate cancer, agnashay cancer aur garbhashay grieva kaa cancer shamil hain. uchch tii. tii. jee. abhivyakti metastasis, chemotherapy pratirodh, cumm uttarjeevita darr aur aam taur parr kharaab purvanuman key uchch udaharanon key saath bhee sambandhit haye.  tii. tii. jee. pargaman gatividhi key sakriyan key madhyam seey calcium key star koo badhaakar cancer koshikaon koo maaraa jaa sakata haye. poorv naidaanik parikshanon ney cancer-rodhi chikitsiya agents key roop mein tii. tii. jee. avrodhakon kaa upayog karane mein ummeed dikhaai haye. haalaanki, anya adhyayanon ney nott kiya haye kii tii. tii. jee. pargaman gatividhi koo tumour koshika aakramansheelta key avrodh seey jodaa jaa sakata haye.
anya roga.
maanaa jaataa haye kii tii. tii. jee. pratilekhan, vibhedan aur pravaas aur asanjan koo prabhaavit karke alzheimer, parkinson aur shikaar rogon sahit kaee neurodegenerative vikaaron mein yogdan detaa haye. iss tarah key tantrika sambandhi rogon kii visheshta prabhaavit mastishk mein protein koo aapas mein jodane kii badhati gatividhi key kaaran protein key asamanya ektrikaran seey hoti haye. isake alawa, inn vikaaron seey judey vishisht protein tii. tii. jee. key inn vivo aur inn vitro substrate paae gaye hain.
haalaanki tii. tii. jee. shikaar kii bimari seey prabhaavit mastishk key kshetron mein viniyamit haye, haal key ack adhyayan seey pataa chalaa haye kii tii. tii. jee. key badhate star choohon mein bimari kii shuruat aur/yaa pragati koo prabhaavit naheen karate hain.
haal key adhyayanon seey pataa chalata haye kii tii. tii. jee. vigyaapan mein shamil naheen hoe sakata haye kyonki adhyayanon seey pataa chalata haye kii yeh erythrocyte lysis seey judaa huaa haye aur ack kaaran key bajaay bimari kaa ack parinam haye.
tii. tii. jee. koo fefde aur gurde sahit vibhinn angon mein fibrosis key rogjanan seey bhee jodaa gayaa haye. vishesh roop seey, gurde key fibrosis mein, tii. tii. jee. tii. jee. aff. beeta gatividhi koo prabhaavit karane vaale ee. see. aim. key sthirikaran aur sanchay mein yogdan detaa haye.
nidan.
anty-tii. tii. jee. antibody key liye serology ney puraane serological parikshanon (anty-endomiseum, anty-gliadine aur anty-reticulin) koo hataa diyaa haye aur celiac roga kii pehchaan key liye ack majboot samvedansheelta (99 pratishat) aur vishishtata (> 90 pratishat) haye. aadhunik anty-tii. tii. jee. parakh ack pratijan key roop mein maanav punarsanyoji protein parr nirbhar karate hain.
upchaaraatmak.
cergical gond key roop mein tii. tii. jee. kaa upayog karna abhee bhee prayogaatmak haye. iska adhyayan kuchh tumours mein metastasis key ack attenuator key roop mein bhee kiya jaa rhaa haye. tii. tii. jee. ack atyadhik chayanaatmak tii. tii. jee. avarodhak kii gatividhi key madhyam seey hriday fibrosis key ilaaj key liye ack sambhaavit chikitsiya lakshya key roop mein vaadaa dikhaata haye. tii. tii. jee. avrodhakon koo neurodegenerative rogon seey sambandhit vishaakt samavesh key gathan koo rokane key liye bhee dikhaaya gayaa haye. yeh ingit kartaa haye kii tii. tii. jee. avarodhak tii. tii. jee. mastishk seey sambandhit beemariyon kii pragati koo cumm karane key liye ack upkaran key roop mein bhee kaam curr sakate hain.
antahkriyaaen.
tii. jee. 2 enzymatic aur gair-enzymatic donon prakaar kii antahkriyaon mein bhaag letaa haye. calcium kii upasthiti mein glutamine daataa aur lycine daataa samoohon vaale tii. jee. 2 aur isake substrate protein key beach enzymatic antahkriyaaen banati hain. tii. jee. 2 key substrate tii. jee. 2 gatividhi koo prabhaavit karane key liye jaane jaate hain, joe ise baad mein koshika mein vividh javic karyon koo nishpaadit karane mein saksham banaata haye. haalaanki, tii. jee. 2 gatividhiyon koo viniyamit karane mein gair-enzymatic antahkriyaon key mahatva kaa khulasa honah abhee baaki haye. haal key adhyayanon seey pataa chalata haye kii gair-enzymatic antahkriyaaen shaaririk bhoomikaaen nibhaati hain aur sandarbh-vishisht tareeke seey vividh tii. jee. 2 karyon koo saksham karati hain.
arp57.
endoplasmic reticulum protein 57 (arp57), endoplasmic reticulum mein mhc varg aaee anuon parr peptide koo load karane mein shamil ack chepron anu haye.
transglutaminase 2 (tii. jee. 2) ack sarvavyaapi roop seey vyakt (antahkoshikiya key saath-saath baahyakoshikiya) protein haye, jisamen post-translational viniyaman key kaee tareeke hain, jisamen sis-370-saais-371 key beach ack allosteric diasulphide bandhan bhee shamil haye joe enzyme koo baahyakoshikiya matricks mein nishkriya curr detaa haye.
endoplasmic reticulum (aeye. aar.)-nivasi protein 57 (aeye. aar. pee. 57), aeye. aar. mein ack protein joe navjat protein key taha koo badhaava detaa haye aur atirikt koshikiya vatavaran mein bhee maujood haye, mein tii. jee. 2 koo nishkriya karane key liye cellular aur jaiv rasayanik visheshtaen hain. hamane paaya kii aeye. aar. pee. 57 samvardhit maanav naabhi nus endothelial koshikaon (huvex) mein atirikt koshikiya tii. jee. 2 key saath collocalise kartaa haye. arp57 aukseekrit teeji2 ack darr sthiraank key saath joe uparokt chhote anu oxidant kii tulanaa mein 400-2000-gunaa adhik thaa. isake alawa, tii. jee. 2 key liye isaki vishishtata anya sraavit redox protein kii tulanaa mein bhee ullekhaniya roop seey adhik thee, jisamen protein diasulphide isomerase (pdi), arp72, trx, aur quissin sulfhydryl oxidase 1 (qsox1) shamil hain.

