БИОХИМИЯ, 2019, том 84, вып. 8, с. 1051–1075

УДК 577.1

Механизмы некоферментного действия тиамина: белковые мишени и медицинское значение

Обзор

© 2019 В.А. Алешин 1,2, Г.В. Мкртчян 1, В.И. Буник 1,2 *

Московский государственный университет им. М.В. Ломоносова, факультет биоинженерии и биоинформатики, 119991 Москва, Россия

Московский государственный университет им. М.В. Ломоносова, НИИ физико-химической биологии им. А.Н. Белозерского, 119991 Москва, Россия; электронная почта: bunik@belozersky.msu.ru

Поступила в редакцию 27.12.2018
После доработки 21.03.2019
Принята к публикации 07.04.2019

DOI: 10.1134/S0320972519080013

КЛЮЧЕВЫЕ СЛОВА: витамин В1, метформин, p53, серпины, тиамин, тиаминаза, транспорт тиамина.

Аннотация

Тиамин (витамин В1) является предшественником известного кофермента тиаминдифосфата (ТДФ). Высочайшая интенсивность ТДФ-зависимой выработки энергии при окислении глюкозы в мозге определяет критическое значение тиамина для деятельности нейронов. Однако существуют и некоферментные механизмы действия тиамина. Давно известное усиление ацетилхолинового сигнала при совместном выбросе тиамина и ацетилхолина в синаптическую щель на настоящий момент подтверждено такими молекулярными процессами, как фосфорилирование взаимодействующего с ацетилхолиновым рецептором белка рапсина за счет тиаминтрифосфата (ТТФ) и взаимодействие тиамина с рецептором TAS2R1, усиливающее синаптические потоки ионов. Некоферментное взаимодействие с тиаминовыми соединениями показано и для транскрипционного фактора р53, поли(ADP-рибозо)-полимеразы, прионного белка PRNP и ряда ключевых ферментов центрального метаболизма, не использующих ТДФ в качестве кофермента. Таким образом, анализ полученных результатов указывает на значительно большее, чем обычно полагают, разнообразие механизмов нейротропного действия тиамина. С этими механизмами тесно связан метаболизм тиаминовых соединений в клетках животных, современные представления о котором также суммированы в обзоре. Актуальность тематики продемонстрирована на примере недавно установленной конкуренции тиамина и широко применяемого антидиабетического препарата метформина за общие внутриклеточные транспортеры. Конкурентный транспорт вызывает дефицит тиамина, лежащий в основе ряда побочных эффектов метформина. В обзоре рассмотрены и такие медицинские аспекты фундаментальных исследований тиамина, как роль тиаминаз в реутилизации тиамина и биосинтезе его антагонистов, механизмы действия природных и синтетических антагонистов тиамина, биотрансформация используемых в медицине фармакологических форм тиамина. Широкая практика лекарственного применения тиамина и его синтетических форм определяет актуальность представленных в обзоре исследований для медицины и фармакологии, включая лечение нейродегенеративных заболеваний.

Сноски

* Адресат для корреспонденции.

Финансирование

Работа выполнена при поддержке Российского фонда фундаментальных исследований (грант № 18-34-00235).

Конфликт интересов

Авторы заявляют об отсутствии конфликта интересов.

Соблюдение этических норм

Настоящая статья не содержит описания не опубликованных авторами результатов исследований с участием людей или использованием животных в качестве объектов.

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