{"id":6446,"date":"2020-07-12T15:26:00","date_gmt":"2020-07-12T12:26:00","guid":{"rendered":"https:\/\/www.ortaakarsu.net\/?p=6446"},"modified":"2020-10-05T16:10:26","modified_gmt":"2020-10-05T13:10:26","slug":"enzim-inhibitoru-ve-inhibisyon-cesitleri","status":"publish","type":"post","link":"https:\/\/www.ortaakarsu.net\/?p=6446","title":{"rendered":"Enzim \u0130nhibit\u00f6r\u00fc ve \u0130nhibisyon \u00c7e\u015fitleri"},"content":{"rendered":"\n<p class=\"wp-block-paragraph\">Enzim inhibit\u00f6r\u00fc enzimlerin \u00e7o\u011funun protein yap\u0131s\u0131nda olmas\u0131 sonucu ortaya \u00e7\u0131kan bir prensiptir. Kanser de dahil olmak \u00fczere pek \u00e7ok hastal\u0131\u011f\u0131n tedavi s\u00fcre\u00e7lerinde enzim inhibit\u00f6r\u00fc niteli\u011finde ila\u00e7lar kullan\u0131lmaktad\u0131r. Anti kanser ajan\u0131 olarak kullan\u0131lan bir enzim inhibit\u00f6r\u00fc i\u00e7in yap\u0131lan bir ara\u015ft\u0131rmay\u0131 daha \u00f6nce <a href=\"https:\/\/www.ortaakarsu.net\/?p=75\">yaz\u0131mda<\/a> incelemi\u015ftir. Protein yap\u0131s\u0131nda olmayan olmayan enzimler ise katalitik RNA molek\u00fclleridir. Enzimlerin yap\u0131lar\u0131n\u0131nn protein yap\u0131l\u0131 oldu\u011fu d\u00fc\u015f\u00fcn\u00fcld\u00fc\u011f\u00fcnde enzimin i\u015flev ve \u00e7al\u0131\u015fma mekanizmalar\u0131 protein yap\u0131n\u0131n konformasyonel b\u00fct\u00fcnl\u00fc\u011f\u00fcne ba\u011fl\u0131d\u0131r. Bu b\u00fct\u00fcnl\u00fc\u011f\u00fcn bozulmas\u0131 enzimin i\u015flevini kal\u0131c\u0131 veya ge\u00e7ici olarak yerine getirememesi demektir. Bu protein yap\u0131s\u0131n\u0131n harici bir molek\u00fcl, atom veya herhangi bir yap\u0131 ile bozulmas\u0131na inhibisyon -yani engelleme denmektedir.<\/p>\n\n\n\n<figure class=\"wp-block-embed-youtube wp-block-embed is-type-video is-provider-youtube wp-embed-aspect-16-9 wp-has-aspect-ratio\"><div class=\"wp-block-embed__wrapper\">\n<div class=\"video-shortcode\"><iframe title=\"Enzyme inhibition\" width=\"1200\" height=\"675\" src=\"https:\/\/www.youtube.com\/embed\/UostSikM888?feature=oembed\" frameborder=\"0\" allow=\"accelerometer; autoplay; clipboard-write; encrypted-media; gyroscope; picture-in-picture; web-share\" referrerpolicy=\"strict-origin-when-cross-origin\" allowfullscreen><\/iframe><\/div>\n<\/div><figcaption>Enzim iinhibisyonunu anlatan bir video. <\/figcaption><\/figure>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Enzim inhibit\u00f6r\u00fc<\/strong> i\u015fleyi\u015fi kovalent olmayan etkile\u015fimlerle oldu\u011fundan her zaman ge\u00e7icidir. Ancak kovalent etkile\u015fim ile meydana gelen inhibisyonda protein yap\u0131n\u0131n b\u00fct\u00fcnl\u00fc\u011f\u00fc tamamen bozularak enzim i\u015flevsiz hale gelir. \u0130nhibisyon i\u015fleyi\u015finin non-kovalent etkile\u015fimler inhibe edildi\u011fi olaylara \u00f6rnek olarak; glutatyon red\u00fcktaz\u0131n, 4-aminokinolin&nbsp;t\u00fcrevi bile\u015fiklerle inhibe edilmesi verilebilirken, kovalent enzim inhibit\u00f6r\u00fc i\u00e7in \u00f6rnek olarak g\u00fcn\u00fcm\u00fczde b\u00fcy\u00fck bir sorun te\u015fkil eden ve t\u00fcm d\u00fcnyaya yay\u0131lm\u0131\u015f olan COV\u0130D-19 vir\u00fcs\u00fcn\u00fcn proteaz enzimine kovalent etkile\u015fim(<a href=\"https:\/\/www.ortaakarsu.net\/?p=95\">glutatyon red\u00fcktaz<\/a> \u00f6rne\u011findeki ki gibi non-kovalent etkile\u015fimler de tabi ki \u00e7al\u0131\u015f\u0131lmaktad\u0131r) yapacak molek\u00fcller aranmaktad\u0131r. Kovalent etkile\u015fim ile inhibisyona ve non-kovalent etkile\u015fim ile inhibisyona ait g\u00f6rseller a\u015fa\u011f\u0131dad\u0131r.<\/p>\n\n\n\n<figure class=\"wp-block-image is-style-default\"><img decoding=\"async\" src=\"https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/image-24.png\" alt=\"kolavent enzim inhibit\u00f6r\u00fc\"\/><figcaption>Kolavent inhibisyona \u00f6rnek olarak, PDB kodu: <a href=\"https:\/\/www.rcsb.org\/structure\/6LU7\">6LU7<\/a> olan COV\u0130D-19 proteaz yap\u0131s\u0131n\u0131 kovalent olarak inhibe eden bir yap\u0131 g\u00f6r\u00fclmektedir.<br><strong>DOI:&nbsp;<\/strong><a href=\"http:\/\/doi.org\/10.2210\/pdb6LU7\/pdb\" target=\"_blank\" rel=\"noreferrer noopener\">10.2210\/pdb6LU7\/pdb<\/a><\/figcaption><\/figure>\n\n\n\n<figure class=\"wp-block-image is-style-default\"><img decoding=\"async\" src=\"https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/image-25.png\" alt=\"enzim inhibit\u00f6r\u00fc enzimi inhibe ediyor\"\/><figcaption>Non-kovalent inhibisyon i\u00e7in ise glutatyon red\u00fcktaz\u0131n bir inhibit\u00f6r taraf\u0131ndan non-kovalent etkile\u015fimlerle inhibe edildi\u011fi yukar\u0131daki g\u00f6rsel \u00f6rnek verilebilir. G\u00f6rsel insan glutatyon red\u00fcktaz enziminin (PDB kodu: <a href=\"https:\/\/www.rcsb.org\/structure\/3DK8\">3DK8<\/a>) bir molek\u00fcl taraf\u0131ndan non-kovalent olarak inhibe edilmesini g\u00f6stermektedir. <br><strong>DOI:&nbsp;<\/strong><a href=\"http:\/\/doi.org\/10.2210\/pdb3DK8\/pdb\" target=\"_blank\" rel=\"noreferrer noopener\">10.2210\/pdb3DK8\/pdb<\/a><\/figcaption><\/figure>\n\n\n<h2><strong><b>Non-Kovalent Enzim \u0130nhibit\u00f6r\u00fc D\u00f6rt \u00c7e\u015fittir<\/b><\/strong><\/h2>\n<p><b>&nbsp;<\/b><strong><b>Yar\u0131\u015fmal\u0131 \u0130nhibisyon ve \u0130nhibit\u00f6rler<\/b><\/strong><\/p>\n<p>Yar\u0131\u015fmal\u0131 \u0130nhibisyonda, substrat ve enzim inhibit\u00f6r\u00fc enzime farkl\u0131 zamanlarda ba\u011flan\u0131r. Bunun yerine enzim inhibit\u00f6r\u00fc substrattan \u00f6nce aktif merkeze ba\u011f yapm\u0131\u015ft\u0131r. Yani substrata ba\u011flancak yer kalmam\u0131\u015ft\u0131r. Bunun olablmesi i\u00e7in tabiki inhibit\u00f6r molek\u00fcl\u00fcn substrattan daha b\u00fcy\u00fck bir ba\u011flanma iste\u011fine sahip olmas\u0131 gerekir.<\/p>\n<p><img decoding=\"async\" src=\"https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/inhibisyon_ornek.png\" sizes=\"(max-width: 320px) 100vw, 320px\" srcset=\"https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/inhibisyon_ornek.png 320w, https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/inhibisyon_ornek-142x300.png 142w\" alt=\"\" width=\"320\" height=\"678\"><\/p>\n\n\n<p class=\"wp-block-paragraph\"><strong>Yar\u0131\u015fmas\u0131z \u0130nhibisyon<\/strong><strong><\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Yar\u0131\u015fmas\u0131z inhibisyonda, enzim inhibit\u00f6r\u00fc substrat-enzim kompleksine ba\u011flan\u0131r. Bu de enzim i\u015flevinin ya tamamen ortadan kalmas\u0131 yada enzim i\u015flevinin yava\u015flamas\u0131 anlam\u0131na gelmektedir. \u0130nhibit\u00f6r substrat enzim kompleksinde enzimdeki olas\u0131 ba\u011flanma b\u00f6lgelerine ba\u011flanarak enzimin protein yap\u0131s\u0131nda konformasyonel bir de\u011fi\u015fme meydana getirir.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Kar\u0131\u015f\u0131k \u0130nhibisyon<\/strong><strong><\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Kar\u0131\u015f\u0131k inhibisyonda, inhibit\u00f6r ve substrat ayn\u0131 zamanda enzime ba\u011flanabilir. Ancak, inhibit\u00f6r\u00fcn ba\u011flanmas\u0131 substrat\u0131n ba\u011flanmas\u0131n\u0131, substrat\u0131n ba\u011flanmas\u0131 da inhibit\u00f6r\u00fcnk\u00fcn\u00fc etkiler. Substrat\u0131n konsantrasyonunu art\u0131rmakla bu tip inhibisyon azalt\u0131labilir ama tamamen \u00fcstesinden gelinemez. Kar\u0131\u015f\u0131k tipli inhibit\u00f6rlerin aktif b\u00f6lgeye ba\u011flanmas\u0131 m\u00fcmk\u00fcn olmakla beraber, bu tip inhibisyon genelde inhibit\u00f6r\u00fcn enzim \u00fczerinde ba\u015fka bir yere ba\u011flanmas\u0131ndan kaynaklanan&nbsp;allosterik&nbsp;bir etkinin sonucudur. \u0130nhibit\u00f6r\u00fcn&nbsp;allosterik yere ba\u011flanmas\u0131, enzimin&nbsp;konformasyonunu&nbsp;de\u011fi\u015ftirir, \u00f6yle ki substrat\u0131n aktif b\u00f6lgeye olan afinitesi azal\u0131r.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Enzim \u0130nhibisyon T\u00fcrlerini A\u00e7\u0131klayan Grafikler<\/strong><\/p>\n\n\n\n<figure class=\"wp-block-image size-large is-resized is-style-default\"><img decoding=\"async\" src=\"https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/image-26.png\" alt=\"Enzim inhibit\u00f6r\u00fc etki mekanizmalar\u0131 \u015fematik g\u00f6sterim\" class=\"wp-image-6455\" width=\"730\" height=\"347\" srcset=\"https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/image-26-300x143.png 300w, https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/image-26-500x238.png 500w, https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/image-26-550x262.png 550w, https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/image-26.png 553w\" sizes=\"(max-width: 730px) 100vw, 730px\" \/><figcaption>Enzim inhibit\u00f6r\u00fc etki mekanizmalar\u0131 \u015fematik g\u00f6sterim<\/figcaption><\/figure>\n\n\n\n<p class=\"wp-block-paragraph\">Yukar\u0131daki \u015fema tersinir inhibisyonun genel bir g\u00f6sterimi olup, enzim inhibisyonunun kineti\u011fi ile ilgili bilgiler vermektedir. ESI inhibit\u00f6r\u00fcn ES kompleksine ba\u011fland\u0131\u011f\u0131n\u0131 ifade etmektedir. Yani bu yar\u0131\u015fmas\u0131z inhibisyonun g\u00f6sterimidir. EI ise yar\u0131\u015fmal\u0131 inhibisyonun g\u00f6sterimidir. \u015eemada g\u00f6r\u00fcld\u00fc\u011f\u00fc gibi \u0130nhibitor ES kompleksi olu\u015fmak yerine EI kompleksi olu\u015fmu\u015f ve enzim inhibe edilmi\u015ftir. Burada her ne kadar yar\u0131\u015fmal\u0131 inhibisyon ve yar\u0131\u015fmas\u0131z inhibisyon bir arada g\u00f6sterilse de ve bir birini takip ediyor olarak g\u00f6r\u00fcnsede iki inhibisyon t\u00fcr\u00fc ayr\u0131 ayr\u0131 da de\u011ferlendirilebilir ve ayr\u0131 ayr\u0131 da etkili \u015fekilde enzim inhibisyonu yapabilir.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Bu \u015femadan yola \u00e7\u0131karak ve tepkimelerin denge halinde oldu\u011funu d\u00fc\u015f\u00fcnerek br tak\u0131m kinetik \u00e7\u0131kar\u0131mlar yapmak m\u00fcmk\u00fcnd\u00fcr. Bu kinetik \u00e7\u0131kar\u0131mlarda elde edilen sonu\u00e7lar\u0131n grafi\u011fe aktar\u0131las\u0131 enzim inhibisyonunun kineti\u011fi hakk\u0131nda \u00f6nemli bilgiler vermektedir.<\/p>\n\n\n\n<figure class=\"wp-block-image size-large is-resized is-style-default\"><img decoding=\"async\" src=\"https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/image-27.png\" alt=\"\" class=\"wp-image-6456\" width=\"511\" height=\"1193\" srcset=\"https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/image-27-129x300.png 129w, https:\/\/www.ortaakarsu.net\/wp-content\/uploads\/image-27.png 404w\" sizes=\"(max-width: 511px) 100vw, 511px\" \/><\/figure>\n\n\n\n<p class=\"wp-block-paragraph\">Yukar\u0131daki grafikler enzim inhibisyonu i\u00e7in enzim inhibit\u00f6r\u00fc t\u00fcrlerinin Lineweaver-Burk grafikleridir. Burada 1\/V de\u011ferlerinin inhibisyon ile ve inhibisyon t\u00fcr\u00fc ile nas\u0131l bir ili\u015fki i\u00e7inde oldu\u011fu g\u00f6r\u00fclmektedir. Yar\u0131\u015fmas\u0131z inhibisyona bakt\u0131\u011f\u0131m\u0131zda 1\/V de\u011feri inhibisyon ile artarak dik ekseni farkl\u0131 yerde kesimi\u015f ve inhibisyon sa\u011flan\u0131\u015ft\u0131r. Bu inhibisyonda 1\/S de\u011ferinin \u00e7\u0131k\u0131\u015f noktalar\u0131 ayn\u0131d\u0131r ve substrat deri\u015fimini g\u00f6stermektedir. Bu konuyla ilgili olarak \u015fuan HIV vir\u00fcs\u00fcn\u00fcn tedavisinde kullan\u0131lan bir ilac\u0131n nas\u0131l \u00e7al\u0131\u015ft\u0131\u011f\u0131 mekanizmas\u0131n\u0131 \u00f6\u011frenmek i\u00e7in <a href=\"https:\/\/www.ortaakarsu.net\/?p=6606\">Raltegravir \u2013 \u0130ntegraz \u0130nhibit\u00f6rlerinin \u0130lki<\/a> bakabilirsiniz. Ayr\u0131ca milli olanaklar ile seri \u00fcretimi yap\u0131\u015fan favicovir ilac\u0131n\u0131n etki mekanizmas\u0131n\u0131, yap\u0131s\u0131n\u0131 ve \u00f6zelleklerini incelemek i\u00e7in <a href=\"https:\/\/www.ortaakarsu.net\/?p=6628\">Favicovir \u2013 Covid-19\u2019a Kar\u015f\u0131 Milli \u0130la\u00e7<\/a> adl\u0131 yaz\u0131y\u0131 okuyabilirsiniz.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Yar\u0131\u015fmal\u0131 inhibisyona bakt\u0131\u011f\u0131m\u0131zda enzim ile etkile\u015fen substrat miktar\u0131nda farkl\u0131la\u015fma vard\u0131r \u00e7\u00fcnk\u00fc inhibit\u00f6r substratla etkili bir bi\u00e7imde yar\u0131\u015fmaktad\u0131r. Bir ligand\u0131n inhibit\u00f6r \u00e7e\u015fitleri bak\u0131m\u0131ndan ayr\u0131nt\u0131l\u0131 incelenmesi bilgisayar sim\u00fclasyonlar\u0131 taraf\u0131ndan hesaplamal\u0131 kimya ile yap\u0131labilmektedir. Bu konu ile ilgili daha \u00e7ok bilgi almak i\u00e7in <a href=\"https:\/\/www.ortaakarsu.net\/?p=6696\">Molek\u00fcler Dinamik Sim\u00fclasyonlar\u0131<\/a> yaz\u0131s\u0131n\u0131 okuyunuz. Yaz\u0131da bir inhibisyon mekan\u0131zmas\u0131n\u0131n bilgisayar sim\u00fclasyonlar\u0131 ile nas\u0131l g\u00f6rselle\u015ftirildi\u011fi anlat\u0131lmaktad\u0131r. <\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Kar\u0131\u015f\u0131k inhibisyonda ise hem yar\u0131\u015fmal\u0131 hem de yar\u0131\u015fmas\u0131z inhibisyonun bir birle\u015fmi oldu\u011funu grafiksel olarak da ortaya koymaktad\u0131r. Hem substrat deri\u015fimi(veya miktar\u0131 da diyebilir) hem de enzimatik tepkimenin devam\u0131nda iki inhibisyon t\u00fcr\u00fcn\u00fcn \u00f6zelliklerini g\u00f6stermektedir.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Enzim inhibisyonunun prensipleri protein yap\u0131lar\u0131n geneli i\u00e7in ge\u00e7erlidir. Buna \u00f6rnek olarak <a href=\"https:\/\/www.ortaakarsu.net\/?p=6899\">Risin Proteini<\/a> ile ilgili yaz\u0131y\u0131 okuyabilirsiniz. <\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Enzim inhibit\u00f6r\u00fc<\/strong> olarak kullan\u0131lan ila\u00e7lar\u0131n nas\u0131l tasarland\u0131\u011f\u0131n\u0131 ve ke\u015ffedildi\u011fini \u00f6\u011frenmek i\u00e7in <a href=\"https:\/\/www.ortaakarsu.net\/?p=6403\">bilgisayar destekli ila\u00e7 tasar\u0131m\u0131n\u0131<\/a> anlatt\u0131\u011f\u0131m\u0131z yaz\u0131ma ve etkili bir <strong>enzim inhibit\u00f6r\u00fc<\/strong> i\u00e7in enzim \u00fczerinde yap\u0131lan in vitro testlerin sonu\u00e7lar\u0131na bakmak i\u00e7in <a href=\"https:\/\/www.ortaakarsu.net\/?p=95\">glutatyon red\u00fcktaz enzim aktivitesi<\/a> yaz\u0131m\u0131za bakabilirsiniz.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Enzim inhibit\u00f6r\u00fc enzimlerin \u00e7o\u011funun protein yap\u0131s\u0131nda olmas\u0131 sonucu ortaya \u00e7\u0131kan  [&#8230;]<\/p>\n","protected":false},"author":1,"featured_media":6448,"comment_status":"open","ping_status":"open","sticky":false,"template":"single-hero-cover.php","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[91],"tags":[102,104,111,109,94,92,125,143,106],"class_list":["post-6446","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-enzimler-biyokimya","tag-enzim-aktivitesi","tag-enzim-inhibisyonu","tag-enzim-inhibitoru","tag-enzim-kinetigi","tag-enzim-turleri","tag-enzimler","tag-ilac","tag-ilac-gelistirme","tag-ilac-kesfi"],"acf":[],"_links":{"self":[{"href":"https:\/\/www.ortaakarsu.net\/index.php?rest_route=\/wp\/v2\/posts\/6446","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.ortaakarsu.net\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.ortaakarsu.net\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.ortaakarsu.net\/index.php?rest_route=\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.ortaakarsu.net\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=6446"}],"version-history":[{"count":0,"href":"https:\/\/www.ortaakarsu.net\/index.php?rest_route=\/wp\/v2\/posts\/6446\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.ortaakarsu.net\/index.php?rest_route=\/wp\/v2\/media\/6448"}],"wp:attachment":[{"href":"https:\/\/www.ortaakarsu.net\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=6446"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.ortaakarsu.net\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=6446"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.ortaakarsu.net\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=6446"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}