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Glyoxalase activity in human erythrocytes and mouse lymphoma, liver and brain probed with hyperpolarized 13C-methylglyoxal.

Published version
Peer-reviewed

Type

Article

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Authors

Kuchel, Philip W 
Hesketh, Richard L 

Abstract

Methylglyoxal is a faulty metabolite. It is a ubiquitous by-product of glucose and amino acid metabolism that spontaneously reacts with proximal amino groups in proteins and nucleic acids, leading to impairment of their function. The glyoxalase pathway evolved early in phylogeny to bring about rapid catabolism of methylglyoxal, and an understanding of the role of methylglyoxal and the glyoxalases in many diseases is beginning to emerge. Metabolic processing of methylglyoxal is very rapid in vivo and thus notoriously difficult to detect and quantify. Here we show that 13C nuclei in labeled methylglyoxal can be hyperpolarized using dynamic nuclear polarization, providing 13C nuclear magnetic resonance signal enhancements in the solution state close to 5,000-fold. We demonstrate the applications of this probe of metabolism for kinetic characterization of the glyoxalase system in isolated cells as well as mouse brain, liver and lymphoma in vivo.

Description

Keywords

0601 Biochemistry and Cell Biology, Biomedical, Clinical Medicine and Science, Rare Diseases, Liver Disease, Digestive Diseases, 2.1 Biological and endogenous factors

Journal Title

Commun Biol

Conference Name

Journal ISSN

2399-3642
2399-3642

Volume Title

1

Publisher

Springer Science and Business Media LLC
Sponsorship
European Commission Horizon 2020 (H2020) Marie Sk?odowska-Curie actions (642773)
Cancer Research Uk (None)
Cancer Research UK (17242)