Fungal enzyme l-lysine α-oxidase affects the amino acid metabolism in the brain and decreases the polyamine level

The fungal glycoprotein l-lysine α-oxidase (LO) catalyzes the oxidative deamination of l-lysine (l-lys). LO may be internalized in the intestine and shows antitumor, antibacterial, and antiviral effects in vivo. The main mechanisms of its effects have been shown to be depletion of the essential amino acid l-lys and action of reactive oxidative species produced by the reaction. Here, we report that LO penetrates into the brain and is retained there for up to 48 h after intravenous injection, which might be explained by specific pharmacokinetics. LO actively intervenes in amino acid metabolism in the brain. The most significant impact of LO was towards amino acids, which are directly exposed to its action (l-lys, l-orn, l-arg). In addition, the enzyme significantly affected the redistribution of amino acids directly associated with the tricarboxylic acid (TCA) cycle (l-asp and l-glu). We discovered that the depletion of l-orn, the precursor of polyamines (PA), led to a significant and long-term decrease in the concentration of polyamines, which are responsible for regulation of many processes including cell proliferation. Thus, LO may be used to reduce levels of l-lys and PA in the brain. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.

Авторы
Lukasheva E.V. 1 , Makletsova M.G. 2 , Lukashev A.N. 3 , Babayeva G. 1 , Arinbasarova A.Y.4 , Medentsev A.G. 4
Журнал
Издательство
MDPI AG
Номер выпуска
11
Язык
Английский
Страницы
1-13
Статус
Опубликовано
Номер
398
Том
13
Год
2020
Организации
  • 1 Department of Biochemistry, Peoples’ Friendship University of Russia (RUDN University), 6 Miklukho-Maklaya St., Moscow, 117198, Russian Federation
  • 2 Department of Biology and General Pathology, Don State Technical University, Gagarin Square 1, Rostov-on-Don, 344011, Russian Federation
  • 3 Martsinovsky Institute of Medical Parasitology, Tropical and Vector Borne Diseases, I.M. Sechenov First Moscow State Medical University (Sechenov University), 20 M. Pirogovskaya str., Moscow, 119435, Russian Federation
  • 4 G.K. Skryabin Institute of Biochemistry and Physiology of Microorganisms, Russian Academy of Sciences, PSCBR RAS, 5 Pr. Nauki, Moscow Region, Pushchino, 142290, Russian Federation
Ключевые слова
Brain; L-amino acid oxidase; L-lysine α-oxidase; Metabolism; Polyamines
Дата создания
20.04.2021
Дата изменения
20.04.2021
Постоянная ссылка
https://repository.rudn.ru/ru/records/article/record/72597/
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