D-glutamine and D-glutamate metabolism

D-glutamine and D-glutamate metabolism refers to the biochemical pathway (KEGG map00471) responsible for the synthesis, interconversion, and utilization of the D-enantiomers of glutamine and glutamate. In bacteria, D-glutamate is an essential component of the peptidoglycan layer of the cell wall, providing the necessary cross-linking and resistance to most proteases [7, 10]. The primary therapeutic target within this pathway is glutamate racemase (MurI), an enzyme that catalyzes the cofactor-independent conversion of L-glutamate to D-glutamate [6, 11]. Because humans lack glutamate racemase and do not incorporate D-glutamate into their proteins, this pathway is a highly attractive target for the development of narrow- and broad-spectrum antibiotics, particularly for treating multi-drug resistant infections like tuberculosis [6, 12]. Beyond its role in infectious diseases, dysregulation of this pathway has been identified as a metabolic signature in several human conditions, including metabolic syndrome and various cancers, where it may serve as a biomarker for disease progression or a target for metabolic reprogramming [14, 16].

Other names

KEGG pathway map00471D-glutamate metabolismD-amino acid metabolismPeptidoglycan biosynthesis pathway

Inhibition of glutamate racemase (MurI), which prevents the conversion of L-glutamate to D-glutamate, an essential component of the bacterial peptidoglycan cell wall [6, 7].