Lukasheva Elena V, Makletsova Marina G, Lukashev Alexander N, Babayeva Gulalek, Arinbasarova Anna Yu, Medentsev Alexander G
Department of Biochemistry, Peoples' Friendship University of Russia (RUDN University), 6 Miklukho-Maklaya St., Moscow 117198, Russia.
Department of Biology and General Pathology, Don State Technical University, Gagarin Square 1, Rostov-on-Don 344011, Russia.
Pharmaceuticals (Basel). 2020 Nov 17;13(11):398. doi: 10.3390/ph13110398.
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.
真菌糖蛋白L-赖氨酸α-氧化酶(LO)催化L-赖氨酸(L-lys)的氧化脱氨反应。LO可能在肠道内被内化,并在体内表现出抗肿瘤、抗菌和抗病毒作用。其作用的主要机制已被证明是必需氨基酸L-lys的消耗以及该反应产生的活性氧化物质的作用。在此,我们报告LO可穿透进入大脑,并在静脉注射后在大脑中保留长达48小时,这可能由特定的药代动力学来解释。LO积极干预大脑中的氨基酸代谢。LO对氨基酸的影响最为显著,这些氨基酸直接暴露于其作用之下(L-lys、L-orn、L-arg)。此外,该酶显著影响与三羧酸(TCA)循环直接相关的氨基酸的重新分布(L-asp和L-glu)。我们发现,多胺(PA)的前体L-orn的消耗导致多胺浓度显著且长期降低,而多胺负责调节包括细胞增殖在内的许多过程。因此,LO可用于降低大脑中L-lys和PA的水平。