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

brain l-amino acid oxidase l-lysine α-oxidase metabolism polyamines

Journal

Pharmaceuticals (Basel, Switzerland)
ISSN: 1424-8247
Titre abrégé: Pharmaceuticals (Basel)
Pays: Switzerland
ID NLM: 101238453

Informations de publication

Date de publication:
17 Nov 2020
Historique:
received: 27 09 2020
revised: 08 11 2020
accepted: 14 11 2020
entrez: 20 11 2020
pubmed: 21 11 2020
medline: 21 11 2020
Statut: epublish

Résumé

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.

Identifiants

pubmed: 33212812
pii: ph13110398
doi: 10.3390/ph13110398
pmc: PMC7698073
pii:
doi:

Types de publication

Journal Article

Langues

eng

Subventions

Organisme : RUDN University
ID : Program 5-100

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Auteurs

Elena V Lukasheva (EV)

Department of Biochemistry, Peoples' Friendship University of Russia (RUDN University), 6 Miklukho-Maklaya St., Moscow 117198, Russia.

Marina G Makletsova (MG)

Department of Biology and General Pathology, Don State Technical University, Gagarin Square 1, Rostov-on-Don 344011, Russia.

Alexander N Lukashev (AN)

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, Russia.

Gulalek Babayeva (G)

Department of Biochemistry, Peoples' Friendship University of Russia (RUDN University), 6 Miklukho-Maklaya St., Moscow 117198, Russia.

Anna Yu Arinbasarova (AY)

G.K. Skryabin Institute of Biochemistry and Physiology of Microorganisms, Russian Academy of Sciences, PSCBR RAS, 5 Pr. Nauki, Pushchino, Moscow Region 142290, Russia.

Alexander G Medentsev (AG)

G.K. Skryabin Institute of Biochemistry and Physiology of Microorganisms, Russian Academy of Sciences, PSCBR RAS, 5 Pr. Nauki, Pushchino, Moscow Region 142290, Russia.

Classifications MeSH