Modeling of Ex Vivo Internalization Method of Water- Soluble Anticancer Drugs in Small Intestine Using Chemiluminescence

Трещалина, Е. М.; Черкасова, Ж Р; Andronova, N. A.; Лукашева, Е. В.; Бабаева, Г.; Клинский, Е. Ю.; Трещалин, М. И.; Цуркан, С А

doi:10.21294/1814-4861-2019-18-6-75-81

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“…l -Orn is a precursor of the polyamines (PA) putrescine, spermine, and spermidine, which show diverse regulatory effects in the body. Recently, it was shown that LO can be internalized in the gastrointestinal tract [ 15 ]. As LO cleaves aliphatic positively charged AAs and can penetrate cells, we reasoned that it might be able to affect the metabolism of AAs and derive PA in the brain.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2020

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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.

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Section: Introductionmentioning

confidence: 99%