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.

Authors
Lukasheva E.V. 1 , Makletsova M.G. 2 , Lukashev A.N. 3 , Babayeva G. 1 , Arinbasarova A.Y.4 , Medentsev A.G. 4
Journal
Publisher
MDPI AG
Number of issue
11
Language
English
Pages
1-13
Status
Published
Number
398
Volume
13
Year
2020
Organizations
  • 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
Keywords
Brain; L-amino acid oxidase; L-lysine α-oxidase; Metabolism; Polyamines
Date of creation
20.04.2021
Date of change
20.04.2021
Short link
https://repository.rudn.ru/en/records/article/record/72597/
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