
kaahil saikkil

alanine saikkil allengil glucose-alanine saikkil ennum ariyappedunna kaahil saikkil, peshikalil ninnulla amino grouppukalum kaarbanukalum karalilekku kondupookunna prathikaranangalude parambarayaanu. asthikooda pesikalkkum karalinum idayil poshakangalude saiklingile koorii saikkilumayi ithu valare saamyamullathaan. oorjja aavasyangalkkaayi peshikal amino aasidukale tharamthaazhthumbol, thathfalamaayundaakunna naitrajan pairuvettilekku traansaminettu cheyth alanine roopappedunnu. ell-glutamatineyum pairuvettineyum α-kettogloottaarett, ell-alanine ennivayaayi parivartthanam cheiyunna alanine transaminase (alt) enna ensaimaanu ithu nadathunnathu. thathfalamaayundaakunna ell-alanine karalilekku shuttle cheyyappedukayum avide naitrajan euria chakratthilekku praveshikkukayum pairuvettu glucose nirmmikkaan upayogikkukayum cheiyunnu.
alanainil ninnulla oorjja ulppaadanathinte upolppannam yooriyayude ulppaadanamaayathinaal laaktett upayogikkunna koorii cyclekkaal kuranja ulpaadanakshamathayaanu kaahil sykkilil ullathu. euria neekkam cheiyunnathu oorjjathe aasrayichirikkunnu, ithinu naalu "uyarnna oorjja" phoosphett bondukal (3 atp hydrolysed tuu 2 adp, oru ampere) aavasyamaanu, athinaal uthppaadippikkunna nettu atp koorii sykkilil kaanapedunnathinekkaal kuravaanu. ennirunnaalum, koorii chakratthil ninnu vyathyasthamayi, laaktett roopappedaathathinaal nadhu samrakshikkappedunnu. ithu electron transport cheyin vazhi ooksidais cheyyaan anuvadikkunnu.
karalumaayi bandhapetta rogangalkkum arbudangalkkumulla puthiya chikilsakal vikasippikkunnathil kaahil chakratthinte klinikkal prasakthi padanangal theliyichittundu.
prathikaranangal.
branch cheyin amino aasidukalude thakarchayil ulppaadippikkunna amonium ionukal surakshithamaayi neekkam cheyyaan euria saikkil upayogikkaan asthikooda peshikalkk kazhiyaathathinal, athu mattoru reethiyil ozhivaakkanam. angane cheiyunnathinu, amonium koshatthile transamination prathikaranatthiloode free α-kettogloottarettumaayi samyojippichu glutamate, α-keetto assid enniva nalkunnu. glutamic-pyroovik transaminase (jipidi) ennum ariyappedunna alanine aminotransaminase (alt), glutamatine veendum α-kettogloottaarettilek maraykkunnu, ithavana glycolysisinte falamaayi amonium pairoovettilekku maattukayum swatantra alanine roopappedukayum cheiyunnu. alanine amino assid oru shuttle aayi pravartthikkunnu-ithu koshatthil ninnu purathukadannu rakthapravaahathilekk praveshikkukayum karalile hepattosaittukalilekka sanjarikkukayum cheiyunnu, avide pradhaanamaayum eee muzhuvan prakriya vipareethamaakunnu. alanine free α-kettogloottarettumaayi oru transamination prathikaranatthinu vidheyamaakukayum glutamate uthpaadippikkukayum cheiyunnu, athu pinneedu deemineet cheyth pairuvettu roopappedukayum aathyanthikamayi free amonium ayoon roopappedukayum cheiyunnu. euria chakratthiloode visha amonium metabolis cheyyaan hepattosaittukalkk kazhiyum, angane athu surakshithamaayi neekkam cheiyunnu. amonium ayonile peshi koshangale vijayakaramaayi neekkam cheytha sesham, eee chakram oorjjam nashtappetta asthikooda peshi koshangalkk glucose nalkunnu. hepattosaittukalile glutamate demination cheiyunnathil ninnu roopappedunna pairuvettu gluconiogenesine vidheyamaayi glucose roopeekarikkunnu, athu rakthapravaahathilekk praveshikkukayum asthikooda peshi koshangalilekku shuttle cheyyukayum angane athinu aavashyamaaya oorjja srothass nalkukayum cheiyunnu.
pravartthanam.
vishamulla amonium ayoninte peshi koshangale neekkam cheiyunnathinum oorjjam nashtappetta peshi koshangalkk parokshamaayi glucose nalkunnathinumulla oru reethiyaayi kaahil saikkil aathyanthikamayi pravartthikkunnu. deerghakaala upavaasathil, glycojan thakarunnathil ninnu ulppaadippikkunna glucosinu anubandhamaayi oru oorjja srotassaayi upayogikkaan asthikooda peshikale tharamthaazhthaam. branch cheyin amino aasidukalude thakarcha oorjja aavasyangalkkaayi upayogikkunna kaarban asthikoodavum swatantra amonium ionukalum nalkunnu. ennirunnaalum, sasthanikalallaatha kasherukkalil athinte saannidhyavum shaareerika praadhaanyavum vyakthamalla. udaaharanathinu, chila malsyangal alanine naitrajan vaahakanayi upayogikkunnundengil, glucose vittuvarav nirakk kurayunnathum peshi tissue vyayaamam cheiyunnathil ninnu alanine purathuvidunnathu kurravaayathum kaaranam eee chakram nadakkaan saadhyathayilla.
asthikooda peshikalileyum karalileyum kaarban asthikoodangalude punarulppaadanam, karalilekku amonium kondupokunnathilum yooriyayayi parivartthanam cheiyunnathilum pankaalittham thudangiya mattu uddeshyangalum alanine chakram niravettunnu.
hepatic (karal) mitocondrial ooksideshan niyanthrikkunnathil, prathyekichu deerghakaala upavaasa kaalayalavil glucose-alanine chakram nerittu panku vahikkumennu padanangal theliyichittundu. citric assid saikilum auxidative phosphorylation ulppedunna glucosinteyum phaatti aasidukaludeyum mettabolisatthile oru pradhana prakriyayaan hepatic mitocondrial ooksideshan. noonn-alcoholic phaatti liver disease (nafld), noonn-alcoholic steettoheppattaitti (naash), type 2 prameham thudangiya rogangalkk madhyasthatha vahikkunnathil hepatic mitocondrial ooksideshane swaadheenikkunna gadakangal manasilaakkunnath valia thaalpparyamulla kaaryamaan. atharam rogangalkk targettucheythathum targettucheyyaathathumaaya chikilsakal vikasippikkunnathinayi hepatic mitocondrial ooksideshante niyanthrana punk prayojanappedutthaan sramikkukayaanu nilavile sajeevamaaya gaveshana mekhala. glucose-alanine chakram eee pradhana gadakangalilonnaayirikkaam. elikalil ninnum manushyaril nadatthiya oru padanatthil kaanikkunnath, 60 manikkoor upavaasa kaalayalavil alanine vittuvarav kurayunnathu hepatic mitocondrial ooksideshanile sradheyamaaya kuravumaayi bandhappettirikkunnu, raathriyil 12 manikkoor upavaasam cheythavare apekshichu. mitocondrial ooksideshan prakriyayile nirnaayaka ensaimaaya sitrettu synthase flexinte (vii. sii. ezz) nirakkukal nireekshichaanu auxidative pravartthanatthinte nirakk praadhamikamaayi alannathu. glucose-alanine chakratthinu nireekshicha falavumaayi kaaryakaaranaparamaaya bandhamundo illayo ennu sthireekarikkunnathinu, athe upavaasa saahacharyangalkk vidheyamaaya oru dvitheeya koottam rogikalkku pinneedu ell-alanine kuthivachu. infusion sesham, 60 manikkoor upavaasam cheytha rogikal hepatic mitocondrial ooksideshanil ganyamaaya vardhanavu kaanichu, ithu bandham sthireekarikkunnu.
oongolajikkal (cancer) rogakaarikalil glucose-alanine chakram ganyamaaya klinikkal prasakthiyundaakam. hepatosellulaar carsinomayude (echu. sii. sii) upapachayam punarnirmmikkunnathil glucose-alanine chakratthinte punk 2020 leeii oru patanam paryavekshanam cheythu. karal kaansarinte ettavum saadhaaranamaaya roopavum lokamembaadumulla kaansarumaayi bandhapetta maranangalude moonnaamathe ettavum saadhaaranamaaya kaaranavumaanu echu. sii. sii. nilavil labhyamaya chikilsakalkku (sasthrakriya, radio therapy, chemotherapy) saadhaaranayaayi gurutharamaaya paarshwafalangalum koodaathe/allengil echu. sii. sii. yill kuranja vijaya nirakkum ullathinaal badal chikitsa oopshanukalkaayulla thirayal gaveshanathinte labhakaramaaya oru mekhalayaayi thudarunnu. druthagathiyilulla valarchaykkum vyapanathinum anukoolamaaya pothuvaaya hyper-metaboolik avastha kaaranam cancer koshangalude sellular mettabolisathe lakshyamidunnathaanu niravadhi puthiya badal koodaathe/allengil anubandha chikilsakalude oru saadhaarana savisheshatha. aarogyamulla koshangalekkaal valare vegathil glucose kazhikkunnathinoppam, cancer koshangal avarude poshaka aavasyangal niravettunnathinaayi amino assid mettabolisathe valareyadhikam aasrayikkunnu. eee padanatthil earppettirikkunna gaveshakar glucose-alanine chakratthiloode samskaricha exogenous alanine poshakakkuravulla anthareekshathil echu. sii. sii koshangalude badal oorjja srothassukalil onnaanennum eee aashrithathvam targettucheytha therapic upayogikkaamennum anumaanichu. ithu pareekshanaathmakamaayi theliyikkunnathinayi, echu. sii. sii koshangal poshakangalude abhaavathil inn vitroyil samskarikkukayum thudarnnu alanine vitharanam cheyyukayum cheythu. metaboolik reprogramming ennu vilikkunna oru prathibhasamaaya eee saahacharyangalil echu. sii. sii koshangalude valarchaye prolsaahippikkaan alanine praarthana mathiyaayirunnu. aduthathaayi, avar amithamaya aavishkaaravum pravartthana nashtavum sambandhicha pareekshanangalude oru parambara nadathukayum echu. sii. sii koshangalile alanine vittuvaravil praadhamikamaayi ulppedunna jipidi isomeraanu glutamic pairuvettu transaminase 1 (jipidi 1) ennu nirnnayikkukayum cheythu, jipidi 1 karalil kaanapedunnu enna muun kandethalukalumayi poruthappedunnu. jii. pii. tii. 1-nte swaabhaavikamaayi sambhavikkunna inhibittaraaya berberin upayogichu metabolikkalaayi punerprogramid echu. sii. sii koshangale chikithsichukondu avar munnott pooyi; nireekshicha swaadheenam eiii. tii. pii ulppaadanavum thudarnnu alanine vitharanam cheiyunna cancer koshangalude valarchayum thadayuka ennathaayirunnu. glucose-alanine chakratthile gadakangal, prathyekichu jipidi 1, badal echsisi chikilsakalkkulla lakshyamaayi oru nalla thiranjeduppaayirikkaanum sasyangalil ninnu uruthirinja selective jipidi 1 inhibittar enna nilayil berberinu eee puthiya marunnukalilonnil upayogikkaan kazhiyumennum avarude patanam theliyichu. cancer koshangalkkulla oru badal indhanamenna nilayil alanine enna ashayam pancreatic cancer koshangalil nadatthiya mattu padanangalilum samaanamaayi prakadamaayirunnu.

