Can Macromolecular Crowding Help Regulate Glutamate Dehydrogenase Activity?

Document Type

Article

Publication Date

10-31-2025

Publication Title

ACS Omega

Abstract

Glutamate dehydrogenase (GDH) is an important mitochondrial enzyme that is positioned at the intersection of several central metabolic pathways. Since this enzyme influences the flux of crucial metabolites, GDH activity is tightly controlled by a complex network of allosteric effectors, and disruption of this regulation has been correlated with a growing list of diseases. To better understand how the crowded environment and pH fluctuations of the mitochondrial matrix contribute to the fine-tuning of GDH regulation, Michaelis-Menten kinetics were measured in the presence of both synthetic and protein crowding agents. The results show a pH-dependent decrease in the GDH activity regardless of crowder identity. Specifically, macromolecular crowding favors the closed GDH conformation, thereby slowing product release. In addition, the presence of dextran increases the p

Volume

10

Issue

44

First Page

53060

Last Page

53073

DOI

10.1021/acsomega.5c07618

ISSN

2470-1343

PubMed ID

41244384

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