{"id":9192,"date":"2020-12-20T20:53:58","date_gmt":"2020-12-20T17:53:58","guid":{"rendered":"http:\/\/blog.ulubat.org\/?p=9192"},"modified":"2020-12-20T21:24:58","modified_gmt":"2020-12-20T18:24:58","slug":"parkinson-hastaligina-kirmizi-mucizedomatesten-l-dopa-uretimi","status":"publish","type":"post","link":"https:\/\/blog.ulubat.org\/index.php\/genel\/parkinson-hastaligina-kirmizi-mucizedomatesten-l-dopa-uretimi\/","title":{"rendered":"PARK\u0130NSON HASTALI\u011eINA KIRMIZI MUC\u0130ZE:DOMATESTEN L-DOPA \u00dcRET\u0130M\u0130"},"content":{"rendered":"\n<figure class=\"wp-block-image\"><img loading=\"lazy\" width=\"1024\" height=\"1024\" src=\"https:\/\/blog.ulubat.org\/wp-content\/uploads\/2020\/12\/image-4-1024x1024.png\" alt=\"\" class=\"wp-image-9193\" srcset=\"https:\/\/blog.ulubat.org\/wp-content\/uploads\/2020\/12\/image-4-1024x1024.png 1024w, https:\/\/blog.ulubat.org\/wp-content\/uploads\/2020\/12\/image-4-150x150.png 150w, https:\/\/blog.ulubat.org\/wp-content\/uploads\/2020\/12\/image-4-250x250.png 250w, https:\/\/blog.ulubat.org\/wp-content\/uploads\/2020\/12\/image-4-125x125.png 125w, https:\/\/blog.ulubat.org\/wp-content\/uploads\/2020\/12\/image-4-110x110.png 110w, https:\/\/blog.ulubat.org\/wp-content\/uploads\/2020\/12\/image-4-768x768.png 768w\" sizes=\"(max-width: 1024px) 100vw, 1024px\" \/><\/figure>\n\n\n\n<p class=\"has-drop-cap has-medium-font-size\">Parkinson dendi\u011finde akl\u0131n\u0131za ne geliyor? Tremor\n(titreme)? Rijidite (kat\u0131l\u0131k)? Bradikinezi (hareketlerde yava\u015fl\u0131k)? Asl\u0131nda\nb\u00fct\u00fcn bunlar Parkinson hastal\u0131\u011f\u0131n\u0131n bilinen en yayg\u0131n belirtileri. \u00c7evremizde\nhepimizin hayat\u0131nda en az bir kere g\u00f6rd\u00fc\u011f\u00fc Parkinson hastalar\u0131 vard\u0131r. Peki bu\nhastal\u0131\u011f\u0131n tedavisiyle alakal\u0131 neler biliyoruz? \u0130la\u00e7lar\u0131n maliyeti uygun mu\nacaba?<\/p>\n\n\n\n<p class=\"has-medium-font-size\"> Biz b\u00fct\u00fcn bunlar\u0131 sorgulayadururken ge\u00e7en ay bilim d\u00fcnyas\u0131nda L-DOPA\u2019yla alakal\u0131 yeni bir ara\u015ft\u0131rma yay\u0131mland\u0131. Acaba g\u00fcn\u00fcm\u00fczde s\u0131k\u00e7a t\u00fcketilen meyvelerden biri olan domates, hem L-DOPA kayna\u011f\u0131 olarak hem de daha az maliyetli bir \u015fekilde kullan\u0131labilir mi? \u0130lk duydu\u011fumda kula\u011f\u0131ma biraz komik geldi a\u00e7\u0131k\u00e7as\u0131. Fakat ara\u015ft\u0131rman\u0131n ayr\u0131nt\u0131lar\u0131na indik\u00e7e bir\u00e7ok a\u00e7\u0131dan avantaj sa\u011flayaca\u011f\u0131n\u0131 ve bilim d\u00fcnyas\u0131na \u00f6nemli bir katk\u0131da bulunaca\u011f\u0131n\u0131 d\u00fc\u015f\u00fcnd\u00fc\u011f\u00fcm bir ara\u015ft\u0131rma oldu\u011funu fark ettim. Gelin bu ara\u015ft\u0131rmaya hep beraber bir g\u00f6z atal\u0131m:<\/p>\n\n\n\n<div class=\"wp-block-image\"><figure class=\"aligncenter is-resized\"><img loading=\"lazy\" src=\"https:\/\/blog.ulubat.org\/wp-content\/uploads\/2020\/12\/42594986535_fc7cd1db9f_o-1-1024x1024.jpg\" alt=\"\" class=\"wp-image-9200\" width=\"531\" height=\"531\" srcset=\"https:\/\/blog.ulubat.org\/wp-content\/uploads\/2020\/12\/42594986535_fc7cd1db9f_o-1-1024x1024.jpg 1024w, https:\/\/blog.ulubat.org\/wp-content\/uploads\/2020\/12\/42594986535_fc7cd1db9f_o-1-150x150.jpg 150w, https:\/\/blog.ulubat.org\/wp-content\/uploads\/2020\/12\/42594986535_fc7cd1db9f_o-1-240x241.jpg 240w, https:\/\/blog.ulubat.org\/wp-content\/uploads\/2020\/12\/42594986535_fc7cd1db9f_o-1-125x125.jpg 125w, https:\/\/blog.ulubat.org\/wp-content\/uploads\/2020\/12\/42594986535_fc7cd1db9f_o-1-110x110.jpg 110w, https:\/\/blog.ulubat.org\/wp-content\/uploads\/2020\/12\/42594986535_fc7cd1db9f_o-1-768x768.jpg 768w\" sizes=\"(max-width: 531px) 100vw, 531px\" \/><figcaption><strong>El tremoru<\/strong> (<strong>titremesi<\/strong>)<br><\/figcaption><\/figure><\/div>\n\n\n\n<p><\/p>\n\n\n\n<p class=\"has-medium-font-size\">Parkinson hastal\u0131\u011f\u0131, yava\u015f ilerleyen n\u00f6rodejenaratif\nbir beyin hastal\u0131\u011f\u0131d\u0131r. L-DOPA, (Levodopa ya da\nL-3,4-dihidroksifenilalanin) Parkinson hastal\u0131\u011f\u0131n\u0131n tedavisinde alt\u0131n standart\nolarak kullan\u0131lan bir ila\u00e7t\u0131r. Bu ilac\u0131n 2005 y\u0131l\u0131nda piyasa hacmi 101 milyar\ndolar ve y\u0131ll\u0131k 250 tondu. L-DOPA\u2019n\u0131n en yayg\u0131n kayna\u011f\u0131 kimyasal sentez\nolmakla birlikte biyolojik ve do\u011fal kaynaklar\u0131 da mevcuttur. &nbsp;Bu do\u011fal kaynaklardan biri de bitkilerdir.\nS\u0131n\u0131rl\u0131 say\u0131da bitki L-DOPA\u2019y\u0131 tohumlar\u0131nda bulundurur. Bunlardan en \u00f6nemlisi\nve en \u00e7ok inceleneni Mucuna pruriens (kadife fasulyesi)\u2019tir. Fakat bu kaynak\npek ideal olmamakla beraber hasat a\u015famas\u0131ndan nihai evreye kadar bir\u00e7ok sorun\n\u00e7\u0131karmaktad\u0131r. Bu bitki, tahri\u015f ve alerjik reaksiyonlara sebep olan mukunain adl\u0131\nprotein i\u00e7eren t\u00fcylerle kapl\u0131d\u0131r. Ayn\u0131 zamanda Mucuna pruriensin (kadife\nfasulyesi) kendisi de, Parkinson hastalar\u0131nda hal\u00fcsinojenik etki yaratacak\nseviyede triptamin i\u00e7erir. <\/p>\n\n\n\n<p class=\"has-medium-font-size\">L-DOPA bulunduran bitki say\u0131s\u0131n\u0131 art\u0131rmak amac\u0131yla,\ntirozini L-DOPA\u2019ya d\u00f6n\u00fc\u015ft\u00fcrmekten sorumlu enzimi bulundurmayan bir bitki olan\ndomates \u00fczerinde \u00e7al\u0131\u015f\u0131lmaya karar verildi. Son zamanlarda pancarda, tirozinin\nL-DOPA\u2019ya hidroksilasyonunu katalizleyen CYP76AD1 ve CYP17AD6 olmak \u00fczere iki\ngenin varl\u0131\u011f\u0131 ke\u015ffedildi. L-DOPA ile zenginle\u015ftirilmi\u015f domates meyvesi \u00fcretmek\ni\u00e7in hangi genin kullan\u0131lmas\u0131 gerekti\u011fine karar vermek i\u00e7in yerle\u015fik BY4742\nmaya sisteminden yararlan\u0131ld\u0131. Bu maya ekspresyon tahlilleri sonucunda CYP76AD6\u2019n\u0131n\nbitkilerde L-DOPA birikimini daha iyi te\u015fvik etti\u011fi sonucuna var\u0131larak\ndomateslerde L-DOPA birikimini sa\u011flamak i\u00e7in CYP76AD6 tercih edildi.<\/p>\n\n\n\n<h4 style=\"text-align:left\"><\/h4>\n\n\n\n<p class=\"has-medium-font-size\"><strong>Peki L-DOPA\u2019yla zenginle\u015ftirilmi\u015f domatesler nas\u0131l bir avantaja sahip?<\/strong><\/p>\n\n\n\n<figure class=\"wp-block-image\"><img loading=\"lazy\" width=\"1024\" height=\"768\" src=\"https:\/\/blog.ulubat.org\/wp-content\/uploads\/2020\/12\/Kapikacchuh_Telugu-_\u0c15\u0c2a\u0c3f\u0c15\u0c1a\u0c4d\u0c1b\u0c42\u0c03_3013097318-1-1024x768.jpg\" alt=\"\" class=\"wp-image-9212\" srcset=\"https:\/\/blog.ulubat.org\/wp-content\/uploads\/2020\/12\/Kapikacchuh_Telugu-_\u0c15\u0c2a\u0c3f\u0c15\u0c1a\u0c4d\u0c1b\u0c42\u0c03_3013097318-1-1024x768.jpg 1024w, https:\/\/blog.ulubat.org\/wp-content\/uploads\/2020\/12\/Kapikacchuh_Telugu-_\u0c15\u0c2a\u0c3f\u0c15\u0c1a\u0c4d\u0c1b\u0c42\u0c03_3013097318-1-400x300.jpg 400w, https:\/\/blog.ulubat.org\/wp-content\/uploads\/2020\/12\/Kapikacchuh_Telugu-_\u0c15\u0c2a\u0c3f\u0c15\u0c1a\u0c4d\u0c1b\u0c42\u0c03_3013097318-1-768x576.jpg 768w, https:\/\/blog.ulubat.org\/wp-content\/uploads\/2020\/12\/Kapikacchuh_Telugu-_\u0c15\u0c2a\u0c3f\u0c15\u0c1a\u0c4d\u0c1b\u0c42\u0c03_3013097318-1-110x83.jpg 110w, https:\/\/blog.ulubat.org\/wp-content\/uploads\/2020\/12\/Kapikacchuh_Telugu-_\u0c15\u0c2a\u0c3f\u0c15\u0c1a\u0c4d\u0c1b\u0c42\u0c03_3013097318-1-420x315.jpg 420w, https:\/\/blog.ulubat.org\/wp-content\/uploads\/2020\/12\/Kapikacchuh_Telugu-_\u0c15\u0c2a\u0c3f\u0c15\u0c1a\u0c4d\u0c1b\u0c42\u0c03_3013097318-1-573x430.jpg 573w, https:\/\/blog.ulubat.org\/wp-content\/uploads\/2020\/12\/Kapikacchuh_Telugu-_\u0c15\u0c2a\u0c3f\u0c15\u0c1a\u0c4d\u0c1b\u0c42\u0c03_3013097318-1.jpg 1200w\" sizes=\"(max-width: 1024px) 100vw, 1024px\" \/><figcaption> <strong>Mucuna Pruriens (Kadife Fasulyesi)<\/strong> <\/figcaption><\/figure>\n\n\n\n<p><\/p>\n\n\n\n<p><\/p>\n\n\n\n<p class=\"has-medium-font-size\">L-DOPA\u2019n\u0131n baz\u0131 toksik etkileri vard\u0131r. Bu etkilerden\ndolay\u0131 b\u00fcy\u00fcmeyi inhibe ederek verim kay\u0131plar\u0131na sebebiyet verebilir. Bunu\nengellemek i\u00e7in CYP76AD6 geninin a\u015f\u0131r\u0131 ekspresyonunu sa\u011flamak \u00fczere meyveye\n\u00f6zg\u00fc E8 promotoru kullan\u0131ld\u0131. L-DOPA olu\u015fturmak i\u00e7in tirozin t\u00fcketimi; birincil\nmetabolizman\u0131n \u00e7o\u011fu aminoasidi daha y\u00fcksek seviyelerde olu\u015fturmas\u0131na neden\nolurken, domates meyvesindeki aromatik aminoasitler i\u00e7in rekabet eden \u00f6zel\nmetabolitlerin sentezini azaltt\u0131\u011f\u0131 g\u00f6r\u00fcld\u00fc.<\/p>\n\n\n\n<p class=\"has-medium-font-size\">L-DOPA\u2019n\u0131n g\u00fc\u00e7l\u00fc antioksidan etkiye sahip oldu\u011fu da elde edilen ilgin\u00e7 bilgilerden bir tanesi. Domates ve di\u011fer yumu\u015fak meyvelerdeki daha y\u00fcksek seviye antioksidan kapasitesi, olgunla\u015fmaya ba\u011fl\u0131 meyve sertli\u011fi ve patojenlere duyarl\u0131l\u0131kla; L-DOPA birikiminin aras\u0131ndaki ili\u015fki g\u00f6sterilmi\u015ftir. Ve b\u00fct\u00fcn bunlar asl\u0131nda daha uzun raf \u00f6mr\u00fcne i\u015faret etmektedir. <\/p>\n\n\n\n<p class=\"has-medium-font-size\">L-DOPA birikiminin ilgin\u00e7 bir ba\u015fka\n\u00f6zelli\u011fi ise kendili\u011finden melanine polimerizasyonudur. L-DOPA\u2019n\u0131n PPO\u2019lar\ntaraf\u0131ndan Dopa-kinona oksidasyonunu takiben, melanin olu\u015fumu ek enzimler\ngerektirmez. Asl\u0131nda L-DOPA biriktiren meyvelerde melanin d\u00fc\u015f\u00fck seviyelerde\n\u00fcretilirken; L-DOPA i\u00e7eren meyve dokusunun hasarlanma yoluyla hava temas\u0131\nsonucunda melanin art\u0131\u015f\u0131 g\u00f6zlenmi\u015ftir. Melanin sentezi, k\u00f6k uzamas\u0131n\u0131 inhibe\netmesi, lipid peroksidasyonu ve reaktif oksijen t\u00fcrlerinin seviyelerinin\ny\u00fckselmesi yoluyla fitotoksisite ile ili\u015fkilendirilmi\u015ftir. Domates\nayr\u0131ca L-DOPA seviyelerini art\u0131rmak i\u00e7in kullan\u0131labilecek \u00e7ok say\u0131da ek kayna\u011fa\n(meyveye \u00f6zg\u00fc MYB12 hatlar\u0131 gibi) sahiptir. Ayn\u0131 zamanda domates \u00e7ok yayg\u0131n\nolarak yeti\u015ftirildi\u011finden bu mahsul \u00f6l\u00e7ek b\u00fcy\u00fctme i\u00e7in kullan\u0131labilir ve potansiyel\nolarak standartla\u015ft\u0131r\u0131lm\u0131\u015f, do\u011fal kontroll\u00fc bir L-DOPA kayna\u011f\u0131 sunar. <\/p>\n\n\n\n<p class=\"has-medium-font-size\">Sonu\u00e7 olarak bakt\u0131\u011f\u0131m\u0131zda; ticari\nila\u00e7lara eri\u015fimin s\u0131n\u0131rl\u0131 oldu\u011fu yerlerde Parkinson hastal\u0131\u011f\u0131n\u0131n tedavisi i\u00e7in L-DOPA\nkayna\u011f\u0131 olarak, CYP76AD6 gen ekspresyonu sonucunda L-DOPA ile zenginle\u015ftirilmi\u015f\ndomatesin kullan\u0131lmas\u0131n\u0131n uygun oldu\u011fu g\u00f6sterilmi\u015ftir. Tahmini olarak bir kilogram\ndomates ba\u015f\u0131na 150 mg L-DOPA seviyelerinde; L-DOPA domatesleri, mikrobiyal\nfermentasyon sistemlerinden veya hareketsizle\u015ftirilmi\u015f tirozinaz biyo\u00fcretim\nsistemlerinden \u00e7ok daha d\u00fc\u015f\u00fck verim verir. Fakat domateslerin \u00f6l\u00e7ek b\u00fcy\u00fctme \u00fcretimi;\nd\u00fc\u015f\u00fck teknoloji ve b\u00fcy\u00fck yat\u0131r\u0131mlara gerek kalmadan y\u00fcksek verim elde\nedilmesine olanak sa\u011flar. Ayn\u0131 zamanda, L-DOPA\u2019n\u0131n hasat edilen domateslerde\nmelanine maj\u00f6r oksidasyon olmaks\u0131z\u0131n depoland\u0131\u011f\u0131 g\u00f6sterilmi\u015ftir. L-DOPA\nmeyvesinin uzat\u0131lm\u0131\u015f raf \u00f6mr\u00fc domateslerin normalden ge\u00e7 hasat\u0131na imkan vermekle\nberaber L-DOPA i\u00e7eri\u011finin potansiyel olarak artmas\u0131na neden olur. Bu\ndomateslerden safla\u015ft\u0131r\u0131lm\u0131\u015f L-DOPA \u00fcretimi; oksidasyonu azaltmak i\u00e7in askorbat\neklenmi\u015f su-metanol kar\u0131\u015f\u0131mlar\u0131nda homojenle\u015ftirme ve ard\u0131ndan ince tabaka\nkromatografisi gibi kromatografik ay\u0131rma i\u015flemi ile sa\u011flanabilir. \u015eu anda konumlar\u0131\nve\/veya ilac\u0131n maliyetinin sonucu olarak bu \u00f6nemli ilaca eri\u015fimi olmayan\nParkinson hastalar\u0131; yerel, ucuz, d\u00fc\u015f\u00fck teknolojili \u00fcretimin avantaj\u0131 ile bu\nilaca ula\u015fm\u0131\u015f olacaklard\u0131r. <\/p>\n\n\n\n<p class=\"has-medium-font-size\">Ek olarak, Mucuna pruriens (kadife fasulyesi) gibi do\u011fal L-DOPA kaynaklar\u0131n\u0131n; Parkinson hastal\u0131\u011f\u0131 tedavisinde ticari olarak sentezlenen L-DOPA\u2019dan \u00f6nemli \u00f6l\u00e7\u00fcde daha iyi etkiler olu\u015fturdu\u011fu g\u00f6sterilmi\u015ftir. Bitki matriksinin; mucuna \u00f6z\u00fctlerinin terap\u00f6tik etkilerini art\u0131rmada \u00f6nemli rol \u00fcstlendi\u011fi ve kadife fasulyesi \u00e7ekirde\u011fi \u00f6zlerinin, antioksidan etkiyle oksidatif stresin ilerlemesini \u00f6nleyebilece\u011fi de ileri s\u00fcr\u00fclm\u00fc\u015ft\u00fcr. CYP76AD6 eksprese eden domates meyvesinde L-DOPA birikiminden kaynaklanm\u0131\u015f artm\u0131\u015f antioksidan kapasite; bu domateslerin do\u011fal \u00f6zlerinin afrodizyak olarak ya da erkek k\u0131s\u0131rl\u0131\u011f\u0131n\u0131 tedavi etmek amac\u0131yla kullan\u0131lan kadife fasulyesi \u00f6z\u00fctlerinin yerini alabilece\u011fini d\u00fc\u015f\u00fcnd\u00fcrmektedir.  <\/p>\n\n\n\n<p class=\"has-medium-font-size\"><strong>KAYNAK\u00c7A:<\/strong><\/p>\n\n\n\n<ol><li>Breitel, D.,vd.(23 November 2020).\nMetabolic engineering of tomato fruit enriched in L-DOPA, <em>John Innes\nCenter. <\/em>&nbsp;(<a href=\"https:\/\/www.jic.ac.uk\/press-release\/tomatoes-offer-affordable-source-of-parkinsons-disease-drug\/\">https:\/\/www.jic.ac.uk\/press-release\/tomatoes-offer-affordable-source-of-parkinsons-disease-drug\/<\/a>)<\/li><li><a href=\"https:\/\/www.jic.ac.uk\/press-release\/tomatoes-offer-affordable-source-of-parkinsons-disease-drug\/\">https:\/\/www.jic.ac.uk\/press-release\/tomatoes-offer-affordable-source-of-parkinsons-disease-drug\/<\/a><\/li><li><a href=\"https:\/\/www.noroloji.org.tr\/TNDData\/Uploads\/files\/parkinson%20hastal%C4%B1%C4%9F%C4%B1.pdf\">https:\/\/www.noroloji.org.tr\/TNDData\/Uploads\/files\/parkinson%20hastal%C4%B1%C4%9F%C4%B1.pdf<\/a><\/li><li><a href=\"https:\/\/popsci.com.tr\/parkinson-ilacinda-kullanilmak-uzere-gelistirilen-ozel-domates\/\">https:\/\/popsci.com.tr\/parkinson-ilacinda-kullanilmak-uzere-gelistirilen-ozel-domates\/<\/a><\/li><li>Kneissel M.,(October 1996). The tomato E8 gene influences\nethylene biosynthesis in fruit but not in flowers. Plant Physiology. Vol:112,\nNo:2,pp.537-547.<\/li><li><a href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S1096717620301816\">https:\/\/www.sciencedirect.com\/science\/article\/pii\/S1096717620301816<\/a><\/li><\/ol>\n","protected":false},"excerpt":{"rendered":"<p>Parkinson dendi\u011finde akl\u0131n\u0131za ne geliyor? Tremor (titreme)? Rijidite (kat\u0131l\u0131k)? Bradikinezi (hareketlerde yava\u015fl\u0131k)? Asl\u0131nda b\u00fct\u00fcn bunlar Parkinson hastal\u0131\u011f\u0131n\u0131n bilinen en yayg\u0131n<\/p>\n","protected":false},"author":387,"featured_media":9198,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":[],"categories":[1],"tags":[1595,1592,1593,1591,1594,1371],"acf":[],"views":1201,"_links":{"self":[{"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/posts\/9192"}],"collection":[{"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/users\/387"}],"replies":[{"embeddable":true,"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/comments?post=9192"}],"version-history":[{"count":24,"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/posts\/9192\/revisions"}],"predecessor-version":[{"id":9239,"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/posts\/9192\/revisions\/9239"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/media\/9198"}],"wp:attachment":[{"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/media?parent=9192"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/categories?post=9192"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/tags?post=9192"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}