Glutamine (systematic name: 2-amino-4-carbamoylbutanoic acid; one-letter code Q, three-letter code Gln) is a polar, uncharged α-amino acid with a molecular weight of 146.15 g/mol. Its side chain terminates in an amide group rather than the carboxylic acid found in glutamic acid, distinguishing the two structurally similar residues and giving glutamine its characteristic chemical neutrality at physiological pH.
In protein chemistry, glutamine residues appear frequently at positions that require hydrogen-bond donors or acceptors without introducing ionic charge. They also participate in post-translational modifications: transglutaminase enzymes cross-link glutamine side chains to lysine residues, forming isopeptide bonds that stabilise extracellular matrix proteins and fibrin clots. Within peptide synthesis, Gln is one of the residues most prone to deamidation , conversion to glutamic acid , a degradation pathway of particular concern in formulation science and during solid-phase peptide synthesis.
Metabolically, glutamine occupies a central position as a nitrogen donor for purine and pyrimidine biosynthesis and as a carbon source feeding into the tricarboxylic acid (TCA) cycle via glutamate and α-ketoglutarate. It is the primary vehicle by which ammonia is transported non-toxically between tissues in the bloodstream, released principally by skeletal muscle and taken up by the liver, kidneys, and rapidly dividing cells. The kidney uses glutamine catabolism to generate ammonium ions (NH₄⁺) for urinary acid–base regulation.
Glutamine is classified as "conditionally essential": healthy adults synthesise sufficient quantities (predominantly in skeletal muscle) under ordinary circumstances, but endogenous production may be insufficient to meet demand during severe physiological stress such as major surgery, serious burns, or critical illness. Its classification and nutritional status are described in standard amino acid reference frameworks, including those published by the Food and Agriculture Organization of the United Nations and the World Health Organization.
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