A Comprehensive Monograph on D-Glutamine: From Molecular Identity to Emerging Therapeutic Potential

Executive Summary

D-Glutamine, the dextrorotatory enantiomer of the ubiquitous amino acid glutamine, has long been relegated to the periphery of biochemical research, often labeled as an "unnatural" isomer with limited biological significance in mammals. This report provides a comprehensive examination of D-Glutamine (DrugBank ID: DB02174), synthesizing data from chemical databases, metabolic studies, and emerging therapeutic research to construct a nuanced and detailed profile. While its isomer, L-Glutamine, is a cornerstone of mammalian metabolism—serving as a proteinogenic building block, a primary nitrogen shuttle, and a critical fuel for rapidly dividing cells—D-Glutamine follows a starkly different path. It is not incorporated into proteins and does not participate in the canonical glutaminolysis pathway that is vital for many cells, particularly in oncology.

Instead, the biological activity and potential pharmacology of D-Glutamine are almost exclusively dictated by a single enzyme: D-amino acid oxidase (DAAO). This flavoenzyme, primarily located in the kidney, liver, and specific regions of the brain, catalyzes the oxidative deamination of D-Glutamine, producing 2-oxoglutaramate, ammonia, and the reactive oxygen species hydrogen peroxide. This metabolic fate positions D-Glutamine not as a nutrient, but as a potential prodrug whose effects are spatially restricted to tissues expressing DAAO. This mechanism presents a therapeutic paradox: whereas L-Glutamine supplementation is often used for its protective, antioxidant-precursor roles, D-Glutamine administration holds potential for targeted, pro-oxidant cytotoxicity.