Fungal Enzyme <span style="font-variant: small-caps">l</span>-Lysine α-Oxidase Affects the Amino Acid Metabolism in the Brain and Decreases the Polyamine Level

• Main Authors: Elena V. Lukasheva, Marina G. Makletsova, Alexander N. Lukashev, Gulalek Babayeva, Anna Yu. Arinbasarova, Alexander G. Medentsev
• Format: Article
• Language: English
• Published: MDPI AG 2020-11-01
• Series: Pharmaceuticals
• Subjects: metabolism; brain; <span style="font-variant: small-caps">l</span>-lysine α-oxidase; <span style="font-variant: small-caps">l</span>-amino acid oxidase; polyamines
• Online Access: https://www.mdpi.com/1424-8247/13/11/398

The fungal glycoprotein <span style="font-variant: small-caps;">l</span>-lysine α-oxidase (LO) catalyzes the oxidative deamination of <span style="font-variant: small-caps;">l</span>-lysine (<span style="font-variant: small-caps;">l</span>-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 <span style="font-variant: small-caps;">l</span>-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 (<span style="font-variant: small-caps;">l</span>-lys, <span style="font-variant: small-caps;">l</span>-orn, <span style="font-variant: small-caps;">l</span>-arg). In addition, the enzyme significantly affected the redistribution of amino acids directly associated with the tricarboxylic acid (TCA) cycle (<span style="font-variant: small-caps;">l</span>-asp and <span style="font-variant: small-caps;">l</span>-glu). We discovered that the depletion of <span style="font-variant: small-caps;">l</span>-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 <span style="font-variant: small-caps;">l</span>-lys and PA in the brain.