ksmaКубанский научный медицинский вестникKuban Scientific Medical Bulletin1608-62282541-9544Kuban State Medical University10.25207/1608-6228-2022-29-4-75-93ksma-2876Research ArticleПРОБЛЕМНЫЕ СТАТЬИTOPICAL ARTICLEРоль пируватдегидрогеназного комплекса в развитии ишемически-реперфузионного синдромаThe Role of the Pyruvate Dehydrogenase Complex in the Development of Ischemic-Reperfusion Syndromehttps://orcid.org/0000-0002-3649-1361ПоповК. А.PopovK. A.

 Попов Константин Андреевич — кандидат медицинских наук; доцент кафедры фундаментальной и клинической биохимии 

 ул. им. Митрофана Седина, д. 4, г. Краснодар, 350063, Россия 

 Konstantin A. Popov — Cand. Sci. (Med.); Assoc. Prof. of the Department of Fundamental and Clinical Biochemistry

 Mitrofana Sedina str. 4, Krasnodar, 350063, Russia 

naftalin444@mail.ruhttps://orcid.org/0000-0003-1242-6909ДенисоваЯ. Е.DenisovaYa. E.

 Денисова Яна Евгеньевна — ассистент кафедры фундаментальной и клинической биохимии

 ул. им. Митрофана Седина, д. 4, г. Краснодар, 350063, Россия 

 Yana E. Denisova — Assistant of the Department of Fundamental and Clinical Biochemistry 

 Mitrofana Sedina str. 4, Krasnodar, 350063, Russia 

iana.denisova.1994@mail.ruhttps://orcid.org/0000-0002-1787-0040БыковИ. М.BykovI. M.

 Быков Илья Михайлович — доктор медицинских наук, профессор; заведующий кафедрой фундаментальной и клинической биохимии

тел.: +7 (918) 212-55-30

 ул. им. Митрофана Седина, д. 4, г. Краснодар, 350063, Россия 

 Ilya M. Bykov* — Dr. Sci. (Med.), Prof., Head of the Department of Fundamental and Clinical Biochemistry 

 Mitrofana Sedina str. 4, Krasnodar, 350063, Russia 

ilya.bh@mail.ruhttps://orcid.org/0000-0002-5711-6659ЦымбалюкИ. Ю.TsymbalyukI. Yu.

Цымбалюк Игорь Юрьевич — кандидат медицинских наук; ассистент кафедры фундаментальной и клинической биохимии 

 ул. им. Митрофана Седина, д. 4, г. Краснодар, 350063, Россия 

Igor Yu. Tsymbalyuk — Cand. Sci. (Med.), Assistant of the Department of Fundamental and Clinical Biochemistry 

 Mitrofana Sedina str. 4, Krasnodar, 350063, Russia 

igor_ts@inbox.ruhttps://orcid.org/0000-0001-6473-3594ЕрмаковаГ. А.ErmakovaG. A.

Ермакова Галина Алексеевна — соискатель кафедры фундаментальной и клинической биохимии

 ул. им. Митрофана Седина, д. 4, г. Краснодар, 350063, Россия 

 Galina A. Ermakova — Applicant for Cand. Sci. (Med.), of the Department of Fundamental and Clinical Biochemistry 

 Mitrofana Sedina str. 4, Krasnodar, 350063, Russia 

ermakova@front.ruhttps://orcid.org/0000-0002-3276-9733ЗавгородняяА. Г.ZavgorodnyayaA. G.

 Завгородняя Анна Германовна — аспирант кафедры фундаментальной и клинической биохимии

 ул. им. Митрофана Седина, д. 4, г. Краснодар, 350063, Россия 

 Anna G. Zavgorodnyaya — post-graduate student of the Department of Fundamental and Clinical Biochemistry 

 Mitrofana Sedina str. 4, Krasnodar, 350063, Russia 

zavgorodnyaya.anna@bk.ruhttps://orcid.org/0000-0002-2218-4205ШевченкоА. С.ShevchenkoA. S.

 Шевченко Алексей Станиславович — аспирант кафедры фундаментальной и клинической биохимии 

 ул. им. Митрофана Седина, д. 4, г. Краснодар, 350063, Россия 

 Alexey S. Shevchenko — post-graduate student of the Department of Fundamental and Clinical Biochemistry 

 Mitrofana Sedina str. 4, Krasnodar, 350063, Russia 

forester5858@gmail.comФедеральное государственное бюджетное образовательное учреждение высшего образования «Кубанский государственный медицинский университет» Министерства здравоохранения Российской ФедерацииРоссияKuban State Medical University of the Ministry of Healthcare of the Russian FederationRussian Federation2022290820222947593Copyright © Попов К.А., Денисова Я.Е., Быков И.М., Цымбалюк И.Ю., Ермакова Г.А., Завгородняя А.Г., Шевченко А.С., 20222022Попов К.А., Денисова Я.Е., Быков И.М., Цымбалюк И.Ю., Ермакова Г.А., Завгородняя А.Г., Шевченко А.С.Popov K.A., Denisova Y.E., Bykov I.M., Tsymbalyuk I.Y., Ermakova G.A., Zavgorodnyaya A.G., Shevchenko A.S.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://ksma.elpub.ru/jour/article/view/2876

Введение. Одним из ключевых звеньев энергетического метаболизма является пирватдегидрогеназный комплекс (ПДК), на активность которого может быть направлено действие некоторых цитопротекторов. Между тем их роль остается не до конца ясна. Известно, что в опухолевых клетках активация ПДК приводит к инверсии анаэробного гликолиза с усилением генерации свободных радикалов в дыхательной цепи и снижением жизнеспособности. В то же время имеются данные, свидетельствующие об увеличении сопротивляемости нормальных клеток гипоксии и реперфузии.Цель исследования — проанализировать современную информацию о роли ПДК в развитии патобиохимических изменений при ишемически-реперфузионном синдроме и способах метаболической коррекции с использованием средств, способных регулировать активность рассматриваемого мультиферментного комплекса.Методы. Проведен поиск литературных источников в базах данных eLIBRARY и PubMed с выбором статей, опубликованных за последние 10 лет на английском и русском языках, а также включением некоторых классических работ в выбранной области старше 10 лет. Для включения источников литературы рассматривали исследования любого дизайна, отражавшие представления о роли ПДК в развитии патобиохимических изменений при ишемически-реперфузионном поражении разных органов и тканей.Результаты. Литературные данные указывают на снижение активности ПДК в ткани миокарда при инфаркте или сердечной недостаточности, на фоне острой гипоксии снижается активность фермента в скелетных мышцах. Активность ПДК также снижается в условиях хронического стресса и при длительных интенсивных мышечных нагрузках. При этом в ишемическом периоде активность ПДК остается на нормальном уровне, а переход к периоду реперфузии сопровождается резким снижением активности мультиферментного комплекса. Инактивация ПДК, возникающая в данных условиях, может быть реализована путем повреждения активными формами кислорода, а также изменением регуляторного контроля путем фосфорилирования/дефосфорилирования. Ключевая роль ПДК в развитии нарушений энергообмена на фоне ишемически-реперфузионных повреждений позволяет предложить две основные стратегии метаболической коррекции: 1) повышение активности ПДК (активатор — дихлорацетат натрия) или компенсация ее недостатка за счет введения субстратов цикла трикарбоновых кислот (ацетилкарнитин, β-гидроксибутират); 2) защита ПДК от повреждения (антиоксиданты).Заключение. Основой нарушений энергообмена в реперфузионный период является снижение активности ПДК, а модификация его активности является перспективным направлением метаболической профилактики или коррекции ишемически-реперфузионных нарушений.

Background. One of the key components of energy metabolism is the pyruvate dehydrogenase complex (PDC), the activity of which can be targeted by some cytoprotectors. However, their role remains unclear. It is known that the activation of the PDC in tumor cells leads to an inversion of anaerobic glycolysis with an increase in the generation of free radicals in the respiratory chain and a decrease in viability. At the same time, there is evidence of increased resistance of normal cells to hypoxia and reperfusion.Objectives. Analysis of current information on the role of PDC in the development of pathologic biochemical changes in ischemic reperfusion syndrome and methods of metabolic correction using agents for regulating the activity of the considered multienzyme complex. Methods. The bibliographical search was carried out across the eLIBRARY and PubMed databases with a selection of articles published over the past 10 years in the English and Russian languages, as well as some parts of fundamental works in the selected field, published more than 10 years. To be selected for bibliographical review, the article can be of any design, reflecting the ideas about the role of PDC in the development of pathologic biochemical changes in ischemic-reperfusion lesions of various organs and tissues.Results. The bibliographical analysis indicates a decrease in the activity of PDC in myocardial tissue during a heart attack or heart failure, the activity of the enzyme in skeletal muscles decreases against the background of acute hypoxia. PDC activity also decreases under chronic stress and extensive muscular exercise. At the same time, the PDC activity remains at the normal level in the ischemic period, and the transition to the reperfusion period is accompanied by a sharp decrease in the activity of the multienzyme complex. The PDC inactivation occurring under these conditions can result from a damage by reactive oxygen species, as well as by regulatory control changes through phosphorylation/dephosphorylation. Assuming the key role of PDC in the development of energy exchange disorders against the ischemic-reperfusion injuries 2 main strategies might be offered for metabolic correction: 1) an increase in the activity of PDC (activator — sodium dichloroacetate) or compensation for its lack with substrates of the tricarboxylic acids (acetylcarnitine, β-ydroxybutyrate); 2) protection of PDC from damage (antioxidants).Conclusion. The basis of energy exchange disorders in the reperfusion period is a decrease in PDC activity, and modification of its activity is a promising direction for metabolic prevention or correction of ischemic-reperfusion injures.

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The authors declare that there are no conflicts of interest present.