Cargando…

Preparative Biocatalytic Synthesis of α-Ketoglutaramate

α-Ketoglutaramate (KGM) is an underexamined metabolite of L-glutamine in the metabolic pathway of glutaminase II of α-ketoglutarate formation. Presumably, KGM may be a biomarker of hepatic encephalopathy and other hyperammonemic diseases. This metabolite is a substrate for the ω-amidase enzyme and i...

Descripción completa

Detalles Bibliográficos
Autores principales: Nikulin, Maksim, Drobot, Viktor, Švedas, Vytas, Krasnikov, Boris F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8657959/
https://www.ncbi.nlm.nih.gov/pubmed/34884551
http://dx.doi.org/10.3390/ijms222312748
_version_ 1784612620607684608
author Nikulin, Maksim
Drobot, Viktor
Švedas, Vytas
Krasnikov, Boris F.
author_facet Nikulin, Maksim
Drobot, Viktor
Švedas, Vytas
Krasnikov, Boris F.
author_sort Nikulin, Maksim
collection PubMed
description α-Ketoglutaramate (KGM) is an underexamined metabolite of L-glutamine in the metabolic pathway of glutaminase II of α-ketoglutarate formation. Presumably, KGM may be a biomarker of hepatic encephalopathy and other hyperammonemic diseases. This metabolite is a substrate for the ω-amidase enzyme and is used to determine its activity in the study of the biochemistry of various types of cancer. However, the commercial unavailability of KGM hinders its widespread use. Methods for the preparative synthesis of KGM are known, but they either do not provide the proper yield or proper purity of the target product. In this work, a detailed description of the procedures is given that allows the production of KGM with a purity above 97% and a yield of the target product above 75% using L-amino acid oxidase from C. adamanteus as a catalyst of L-glutamine conversion. KGM can be obtained both in the form of a highly concentrated aqueous solution and in the form of crystals of sodium salt. The developed methods can be used both for scaling up the synthesis of KGM and for creating economical biocatalytic technologies for the production of other highly purified preparations.
format Online
Article
Text
id pubmed-8657959
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-86579592021-12-10 Preparative Biocatalytic Synthesis of α-Ketoglutaramate Nikulin, Maksim Drobot, Viktor Švedas, Vytas Krasnikov, Boris F. Int J Mol Sci Article α-Ketoglutaramate (KGM) is an underexamined metabolite of L-glutamine in the metabolic pathway of glutaminase II of α-ketoglutarate formation. Presumably, KGM may be a biomarker of hepatic encephalopathy and other hyperammonemic diseases. This metabolite is a substrate for the ω-amidase enzyme and is used to determine its activity in the study of the biochemistry of various types of cancer. However, the commercial unavailability of KGM hinders its widespread use. Methods for the preparative synthesis of KGM are known, but they either do not provide the proper yield or proper purity of the target product. In this work, a detailed description of the procedures is given that allows the production of KGM with a purity above 97% and a yield of the target product above 75% using L-amino acid oxidase from C. adamanteus as a catalyst of L-glutamine conversion. KGM can be obtained both in the form of a highly concentrated aqueous solution and in the form of crystals of sodium salt. The developed methods can be used both for scaling up the synthesis of KGM and for creating economical biocatalytic technologies for the production of other highly purified preparations. MDPI 2021-11-25 /pmc/articles/PMC8657959/ /pubmed/34884551 http://dx.doi.org/10.3390/ijms222312748 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Nikulin, Maksim
Drobot, Viktor
Švedas, Vytas
Krasnikov, Boris F.
Preparative Biocatalytic Synthesis of α-Ketoglutaramate
title Preparative Biocatalytic Synthesis of α-Ketoglutaramate
title_full Preparative Biocatalytic Synthesis of α-Ketoglutaramate
title_fullStr Preparative Biocatalytic Synthesis of α-Ketoglutaramate
title_full_unstemmed Preparative Biocatalytic Synthesis of α-Ketoglutaramate
title_short Preparative Biocatalytic Synthesis of α-Ketoglutaramate
title_sort preparative biocatalytic synthesis of α-ketoglutaramate
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8657959/
https://www.ncbi.nlm.nih.gov/pubmed/34884551
http://dx.doi.org/10.3390/ijms222312748
work_keys_str_mv AT nikulinmaksim preparativebiocatalyticsynthesisofaketoglutaramate
AT drobotviktor preparativebiocatalyticsynthesisofaketoglutaramate
AT svedasvytas preparativebiocatalyticsynthesisofaketoglutaramate
AT krasnikovborisf preparativebiocatalyticsynthesisofaketoglutaramate