Свободный холестерол

В конце концов ЛНП отделяются от рецепторов (которые возвращаются на поверхность клетки) и попадают в лизосомы — везикулы, содержащие гидролизующие ферменты. Одни ферменты разрушают оболочку ЛНП, обнажая состоящее из эфиров холсстерола ядро, а другие отщепляют от холестерола жирные кислоты. Свободный холестерол затем покидает лизосомы. Как уже говорилось, всем клеткам холестерол нужен для образования поверхностной мембраны. В некоторых специализированных клетках высвобождающийся из ЛНП холестерол играет и иные роли. Так, в клетках надпочечников и яичников он превращается в соответствующие стероидные гормоны — кортизол и эстрадиол. В клетках печени холестерол используется для синтеза желчных кислот, участвующих в пищеварении.

ОТ ТОГО, в каком количестве высвобождается из ЛНП холестерол, зависит его метаболизм. Накопление холестерола влияет на три процесса в клетках. Во-первых, при избытке холестерола подавляется способность клеток к образованию собственного холе- стерола, так как выключается синтез фермента идроксиметилглутарил редуктазы, катализирующего один из этапов биосинтеза холестерола. В результате клетки делаются зависимыми от экзогенного холестерола, поступающего благодаря опосредуемому рецепторами захвату ЛНП. Во- вторых, поступающий с ЛНП холестерол стимулирует запасание его в клетках. Такой эффект обусловлен тем, что при избытке холестерола активируется фермент холестерол-ацилтрансфераза. Этот фермент присоединяет к свободному холестеролу углеводородные цепи жирных кислот с образованием эфиров, которые откладываются в виде капелек; таким образом избыточный холестерол выводится из оборота. Третье и наиболее важное действие избытка холестерола в клетках — запуск механизма обратной связи, останавливающего синтез новых рецепторов ЛНП.

 

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