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. 2020 Nov 17;13(11):398.
doi: 10.3390/ph13110398.

Fungal Enzyme l-Lysine α-Oxidase Affects the Amino Acid Metabolism in the Brain and Decreases the Polyamine Level

Elena V Lukasheva  1 , Marina G Makletsova  2 , Alexander N Lukashev  3 , Gulalek Babayeva  1 , Anna Yu Arinbasarova  4 , Alexander G Medentsev  4
Affiliations

Fungal Enzyme l-Lysine α-Oxidase Affects the Amino Acid Metabolism in the Brain and Decreases the Polyamine Level

Elena V Lukasheva et al. Pharmaceuticals (Basel). .

Abstract

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.

Keywords: brain; l-amino acid oxidase; l-lysine α-oxidase; metabolism; polyamines.

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Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Figure 1
Figure 1
(a) l-lysine α-oxidase concentration (▲, left OX axis) and activity (•, right OX axis) in plasma after single i.v. administration at a dose of 1.5 mg/kg. (b) l-lysine α-oxidase concentration in the brain tissue after single i.v. administration at a dose of 1.5 mg/kg. Number of animals n = 5 at each time point. The values shown are mean of three determinations. Results are presented as mean ± SEM.
Figure 2
Figure 2
The resistance of l-lysine α-oxidase (LO) to proteolysis. LO (0.17 μM) incubation at 37 °C in 0.2 M Tris-HCl buffer (pH 7.8) in the presence of 21.7 μM chymotrypsin (▲), 20 μM trypsin (○), without additives—control (□).
Figure 3
Figure 3
Dynamics of l-lysine structural analogs concentrations in the brain after a single l-lysine α-oxidase injection i.v. at a dose of 1 mg/kg. The results are presented as mean ± SEM, as a ratio to the control group. Difference between experimental and control groups was assessed using one-way ANOVA. Statistically significant difference designated as ** for p < 0.05 or * for p < 0.01.
Figure 4
Figure 4
Dynamics of amino acid concentrations in the brain after a single l-lysine α-oxidase injection i.v. at a dose of 1 mg/kg. The results are presented as mean ± SEM, as a ratio to the control group. Difference between experimental and control groups was assessed using one-way ANOVA. Statistically significant difference designated as ** for p < 0.05 or * for p < 0.01.
Figure 5
Figure 5
Dynamics of PA concentrations in the brain after a single l-lysine α-oxidase injection i.v. at a dose of 1 mg/kg. The results are presented as mean ± SEM, as a ratio to the control group. Difference between experimental and control groups was assessed using one-way ANOVA. Statistically significant difference designated as ** for p < 0.05 or * for p < 0.01.
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