
methylmalonyl-qoo mutase kuravu

oru mitocondrial homodymer apoensaimaanu (iii. sii.) methylmalonyl-qoo mutase. 5. 4.99.2) ithu methylmalonyl kovayude sasinail kovayilekkulla kaattalisisil shradha kendreekarikkunnu. pravarthikkunnathinu vitaamin bii 12-nte hormon derivative aaya adenosylcobalaminumaayi ensime bandhappettirikkunnu. ensaimine encode cheiyunnathinu utharavaadikalaaya myoott jeenile janithaka vaikalyam moolamaanu methylmalonyl-qoo mutase kuravu undaakunnath. eee ensaiminte kuravu methylmalonic acidemiayude 60 sathamaanam kesukalilum kaaranamaakunnu.
lakshanagal.
methylmalonyl qoo mutase kurravulla aalukal mettabolisatthinte janmana ulla pishakukal ulppedunna mattu rogangalkk samanamaaya niravadhi lakshanagal prakadippikkunnu.
navjata sisukkalkku chharddi, acidosis, hyperammonaemia, hepattomegali (karal valuthaakkiyath), hyper glycinamia (uyarnna glycine alavu), hypoglycemia (rakthathile panchasaarayude alavu kurayunnathu) enniva anubhavappedunnu. pinneedu, thrombocytopenia, neutropenia ennivayude kesukal sambhavikkam.
chila sandarbhangalil oottisam polulla boudhikavum vikasanaparavumaya vaikalyangal methylmalonyl-qoo mutase kurravulla janasamkhyayil vardhicha aavruthiyumaayi sradhikkappettu.
kaaranagal.
methylmalonic acidemiaykku janithakavum bhakshanaparavumaya vividha kaaranangalundengilum, methylmalonyl qoo mutase kuravu oru autosomal resussive janithaka thakaraaraan. eee kurravulla rogikalkku onnukil myoott 0 ennu perittirikkunna poornnamaaya jeane kshathamo allengil myoott-ennu perittirikkunna frameshiftinte roopathil bhagikamaaya mutationo undu. eee frameshift ensaiminte madakkine badhikkunnu, ithu athinte binding domaine phalapradamallaathaakkunnu. poornnamaayum illaathaakkiya rogikalkku methylmalonyl qoo mutase nirjjeevamaakkukayum kuravinte ettavum gurutharamaaya lakshanagal prakadippikkukayum cheiyunnu, athesamayam bhagika mutationukalulla rogikalkku vaividhyamaarnna lakshanangalund. myoott jeeninaayi 49-ladhikam vyathyastha mutationukal kandethiyittundu, ennittum rund mutationukal maathrame eathenkilum thirichariyaan kazhiyunna aavruthiyilulloo.
ensaimatik pravartthanam.
methylmalonyl-qoo mutase methylmalonyl-koyude sasinail-qoo aayulla isomerisatione uthejippikkukayum eee kaimaattam poortthiyaakkunnathinu bii 12 ll ninnu uruthirinja prosthettik grouppaaya adenosylcobalamine upayogikkukayum cheiyunnu. mitocondrial maatriksil sthithi cheiyunna oru homodymeranu ensime. 750 amino aasidukal neelamulla eee ensaiminu adenosylcobalamine cobalt mekhalayumaayi bandhippikkunna loha ligand binding mekhalayundu.
adenosylcobalamine sii-qoo (iii) boond vichedichukondu kaarban, cobalt (iii) aattangalkk oro electron nalkikkond ensime pravartthikkunnu. cobalt athinte rund ooksideshan avasthakalkkidayil ettakkurachilukal kaanikkunnu qoo (II), qoo (III). eee reethiyil adenosylcobalamine oru reversible free radical janarettaraayi pravartthikkunnu. athinaal koensaimine oru groupilekku maattunnathinaayi cobalt oru electron methylmalonyl-qoo nattellilekku thirike sambhavana cheiyunnu.
upapachayam pravartthanam.
amino aasidukalum otta-shringhala phaatti aasidukalum ulppede niravadhi thanmaathrakalude apachaya paathakalkk methylmalonyl-qoo mutase athyaavasyamaanu. eee macromoleculukalude propionyl-qoo degradation upolppannathe tricarboxylic assid saikkilumayi methylmalonyl-qoo mutase bandhippikkunnu.
amino assid mettabolisathinu, methylmalonyl-qoo mutase isolucin, thrionin, valin, methionin ennivayude apachaya pathakalil pravartthikkunnu. eee amino aasidukal propanoyil-qoo aayi tharamthaazhthappedunnu, athu pinneedu (kall)-methylmalonyl-qoo aayi tharamthaazhthappedunnu. eee substrate valare samanamaaya ensaimaaya methylmalonyl-qoo epimerase vazhi kooduthal metabolise cheyyanam, ithu methylmalonyl-koyude (kall) roopathe (aarr) roopathilekku parivartthanam cheiyunnu. ithu oduvil methylmalonyl-qoo mutase upayogichu parivartthanam cheyyappedunnu. ell-methionin oru neelamulla soopparpaathveyiloode metabolise cheyyappedunnu (chithram 2 kaanuka). ell-homocystinilekku parivartthanam cheytha sesham, ithu ell-sereenumaayi samyojippichu ell-systethayon nirmmikkunnu, ithu systethayon gaama lies hydrolyse cheyth 2-ooksoobuttaanooyett srishtikkunnu. eee substrate propionyl-qoo aayi parivartthanam cheyyappedukayum propionyl-koykk munbu vivaricha athe mettabolisathinu vidheyamaakukayum cheiyunnu.
collustroll soopparpathve collustroll vividha substrateukalaayi kurayunnathine pinthudarunnu, ennirunnaalum eee bio transformed thanmaathrakalil randennam maathrame propionyl-koye oru upolppannamaayi kaanoo. 3, 24-dioxocolest-4-enn-26-oayil-kova 2-ooksookol-4-enn-24-oayil-kovayilekku parivartthanam cheiyunnathu oru propionyl-qoo thanmaathrayude prakashanam kaanunnu. koodaathe, 3-oakso-23,24-bisnorcol-4-enn-17-ool-22-oayil-koye propionyl-qoo thanmaathrayude aandrost-4-enn-3,17-dion releasaayi parivartthanam cheiyunnu. avasaanamaayi, (kall)-4-hydroxy-2-ooksoheksaanooyett pairuvettu, propanel ennivayaayi kshayichupokukayum, propanel parivartthanam cheythathinushesham oru propionyl-qoo substrate purathuvidukayum cheiyunnu. amino assid mettabolisathinaayulla methylmalonyl paatha pinthudarnnu eee propionyl-qoo substrateukalellaam sasinail-qoo aayi parivartthanam cheyyappedunnu, methylmalonyl-qoo mutase isolucin, thrionin, valin, methionine ennivayude apachaya pathakalil pravartthikkunnu. eee amino aasidukal propanoyil-qoo aayi tharamthaazhthappedunnu, athu pinneedu (kall)-methylmalonyl-qoo aayi tharamthaazhthappedunnu. eee substrate valare samanamaaya ensaimaaya methylmalonyl-qoo epimerase vazhi kooduthal metabolise cheyyanam, ithu methylmalonyl-koyude (kall) roopathe (aarr) roopathilekku parivartthanam cheiyunnu. ithu oduvil methylmalonyl-qoo mutase upayogichu parivartthanam cheyyappedunnu. ell-methionin oru neelamulla soopparpaathveyiloode metabolise cheyyappedunnu (chithram 2 kaanuka). ell-homocystinilekku parivartthanam cheytha sesham, ithu ell-sereenumaayi samyojippichu ell-systethayon nirmmikkunnu, ithu systethayon gaama lies hydrolyse cheyth 2-ooksoobuttaanooyett srishtikkunnu. eee substrate propanoyil-qoo aayi parivartthanam cheyyappedukayum propanoyil-koykk munbu vivaricha athe mettabolisathinu vidheyamaakukayum cheiyunnu.
methylmalonyl paathayiloode otta shringhala phaatti aasidukalum upapachayam cheyyappedunnu. otta shringhala phaatti aasidukalude apachayam asattail-qoo, propionyl-qoo enniva purathuvidunnu. propionyl-qoo pinneedu sasinail-qoo aayi parivartthanam cheyyappedunnu, koodaathe reductantinte thudarchayaaya ulppaadanathinaayi sasinail-qoo, propionyl-qoo enniva tricarboxylic assid saikkililekk interject cheiyunnu.
metaboolik pathology.
tricarboxylic assid saikkil substrate sasinail-koyaanu methylmalonyl-qoo mutase pravartthanatthinte anthima uthppannam. adikamaaya methylmalonyl-koyude paarshwafalamaanu propionyl-koyude mettabolisatthil neratthe mattu parivarthanangalkku kaaranamakunna ensaimukalude thadassamaanu, ithu propanoic acidemiayilekkum nayikkunnu. amithamaya methylmalonyl-qoo aaa paathaye aashrayichirikkunna methylation pathayeyum glutathayoninte roopeekaranatheyum thadayunnathiloode auxidative sammarddathilekku nayikkunnu. ithu mailin, euria, glucose ennivayude jaivasamshleshanathe thadassappeduthunnu. prathyekichum, adikamaaya methylmalonyl-qoo euria sykkilil ulppedunna mitocondrial ensaimukalil (amonia-dependent-carbamoyil-phoosphett synthase allengil sii. pii. ezz 1 polullava) auxidative sammarddam cheluthukayum athinte pravartthana samvidaanathe thadayukayum cheiyunnu. inhibited euria synthesis mosham protein metabolisavum, athupole thanne durbalamaayi veendum niraykkunna tricarboxylic assid saikilum methylmalonic acidemiayude lakshanangalkk kaaranamaakunnu.
roganirnayam.
methylmalonyl-qoo mutasinte pravarthanarahithatha kandethaan niravadhi parisodhanakal nadatthaam. amonia parisodhana, rakthathinte ennam, sidi scan, emri scan, electrolyte alavu, janithaka parisodhana, methylmalonic assid raktha parisodhana, raktha plasma amino assid parisodhanakal ennivayellaam kuravu nirnnayikkaan nadatthaam.
chikitsa.
myoott 0 jeeninte poornnamaaya shathathinu chikithsayillenkilum, cheria janithaka pravarthanakshamathayillaathe sahayikkaan niravadhi chikilsakalkku kazhiyum. karal, vrukka maattivaykkal, kuranja protein bhakshanakramam ennivayellaam rogangalude prathyaaghaathangal niyantrikkaan sahayikkunnu.
pravachanam.
neratheyulla roganirnayam nadathunna rogikalil sisumarananirakku kooduthalaanu; 2 maasathinullil marananirakk sambhavikkam, athesamayam lettu-oonsettu syndrome ulla kuttikalkk athijeevana nirakk kooduthalaanennu thonnunnu. myoott0-nte poornnamaaya shathamulla rogikalkku methylonyl-qoo mutase kuravullavarude ettavum mosham phalam mathramalla, eathenkilum tharatthilulla methylmalonic acidemia ulla ellah vyakthikaludeyum ettavum mosham phalam koodiyaanithu.

