L-glutamine

Glutamine structure confirmation

Record evidence identifying the glutamine structure and resolving plausible related compounds.

1. Which reference identity and analytical observations support assigning this material to L-glutamine? definition
2. Does the method distinguish glutamine from glutamate and other plausible components of this sample? measurement

L-configuration evidence

Keep evidence of handedness separate from evidence of chemical purity.

1. Which stereochemistry-sensitive measurement or traceable reference supports the L assignment? provenance
2. What D-glutamine fraction was measured or bounded, and what uncertainty remains? measurement

Free versus bound glutamine

Record whether the reported amount refers to free material or glutamine released or inferred from another substance.

1. Does the reported glutamine amount mean free L-glutamine, peptide-bound residues or glutamine equivalents? definition
2. Does the sample contain L-alanyl-L-glutamine, another derivative or a distinct salt form requiring a linked identity assessment? boundary

Matrix-qualified material state

Record presentation, matrix and homogeneity so measurements refer to the material actually handled.

1. Is the material a solid, a stock solution or a component of a mixture, and what solvent or matrix surrounds it? definition
2. Is the material fully dissolved or homogeneous at the point of sampling, and how was that established? measurement

Usable glutamine quantity

Record the quantity of free L-glutamine with its basis and uncertainty.

1. What free L-glutamine mass fraction or concentration was measured, by which method and at what time? measurement
2. Does the reported assay use an as-received, dry-mass or chromatographic-area basis, and what corrections are justified? definition

Application-relevant quality evidence

Attach relevant impurity and contamination results without treating a grade label as universal suitability.

1. Which related substances, residual constituents or contamination measures does the proposed use require, and what results are available? measurement
2. Which lot-specific specification supports the claimed grade, including sterility or endotoxin criteria when applicable? provenance

Stability evidence applicability

Determine whether available stability evidence matches this material and its handling history.

1. When was this lot dissolved or opened, and what temperature, pH and freeze-thaw history is documented? provenance
2. Does the cited storage or beyond-use limit cover this concentration, matrix, container and actual exposure history? boundary

Degradation status

Record remaining L-glutamine and relevant degradation measurements with uncertainty.

1. What are the current free L-glutamine, ammonia/ammonium and pyrrolidone carboxylic acid measurements? measurement
2. Could the matrix or biological activity explain the observed ammonia independently of storage degradation? boundary
3. Do the results support continued use, require retesting or exceed the named application's acceptance limits? action

Supported preparation operation

Record an authorised procedure, its required inputs and the evidence needed to assess the resulting preparation.

1. Which procedure governs dissolution, dilution, aliquoting or filtration for the intended use? action
2. What concentration, quality and stability checks must the resulting preparation satisfy before release? action

Glutamine-source substitution

Record what a proposed substitute supplies and route equivalence decisions to the relevant formulation or biological model.

1. Would the proposed replacement supply free L-glutamine directly or require conversion from another molecule? boundary
2. What application-specific evidence supports the replacement amount, availability and accompanying constituents? provenance
3. Which linked model or responsible authority decides whether this substitution is acceptable? action

Kinds and varieties

Reported by the breadth pass; each item needs checking against its source before it becomes normative.

• proteinogenic free L-glutamine (endogenous / dietary amino acid)
• USP/Ph. Eur. pharmaceutical-grade L-glutamine (oral or parenteral amino-acid component)
• food-supplement / sports-nutrition L-glutamine (powder, capsule)
• parenteral nutrition amino-acid mix component (often as L-alanyl-L-glutamine dipeptide, not free glutamine)
• cell-culture / bioprocess L-glutamine (media supplement; also as GlutaMAX-type dipeptide)
• isotopically labelled L-glutamine (13C/15N tracers)
• L-glutamine as a pharmacopeial reference standard
• conditionally essential / stress-state L-glutamine (clinical nutrition use, not a chemical isomer)

1. Which of these kinds and varieties hold for the sense of L-glutamine this model covers, and on what evidence? provenance

Identifiers and schemes

Reported by the breadth pass; each item needs checking against its source before it becomes normative.

• CAS Registry Number - 56-85-9 - L-glutamine (not the racemate or D-enantiomer)
• PubChem CID - 5961 - Compound record for L-glutamine
• IUPAC InChIKey - ZDXPYRJPNDTMRX-VKHMYHEASA-N - Stereospecific key; the racemate/D-form have different stereo layers
• UNII (FDA SRS) - 0RH81L854J - Preferred substance identifier for L-glutamine in US drug listings
• ChEBI - CHEBI:18050 - L-glutamine; parent glutamine is CHEBI:28300
• IUPAC name - (2S)-2,5-diamino-5-oxopentanoic acid - Also (2S)-2-amino-4-carbamoylbutanoic acid
• EC number (EINECS) - 200-292-1 - European inventory number for L-glutamine
• DrugBank - DB00130 - L-glutamine as an approved/nutraceutical substance
• ATC (WHO) - A16AA03 - Glutamine as an alimentary-tract / metabolic product (amino acids and derivatives)
• Wikidata - Q181619 - item for L-glutamine
• HS / trade - 2922.49 (amino-acids and their esters, other) - Typical customs heading for bulk amino acids; confirm with local tariff

1. Which of these identifiers and schemes hold for the sense of L-glutamine this model covers, and on what evidence? provenance

Standards and regulation

Reported by the breadth pass; each item needs checking against its source before it becomes normative.

• United States Pharmacopeia-National Formulary (USP-NF): Glutamine monograph (identity, assay, specific rotation, related compounds) - USP
• European Pharmacopoeia (Ph. Eur.): Glutamine / L-glutamine related monographs and parenteral amino-acid preparation requirements - EDQM / Council of Europe
• FCC (Food Chemicals Codex): L-Glutamine food-grade specification - USP (FCC)
• US FDA: L-glutamine oral powder approved to reduce acute complications of sickle cell disease (Endari, NDA 208587); also GRAS/food-use as an amino acid in conventional foods and supplements under DSHEA when labeled as a dietary ingredient - FDA
• EMA / national EU medicines agencies: glutamine for parenteral nutrition is typically authorised as L-alanyl-L-glutamine (e.g. Dipeptiven) because free glutamine is unstable in heat-sterilised aqueous PN solutions - EMA
• WHO ATC classification A16AA03 (glutamine) - WHO Collaborating Centre for Drug Statistics Methodology
• Codex / JECFA amino-acid food-additive and nutrient evaluations (as applicable to L-amino acids used in foods) - FAO/WHO
• EU food-supplement and novel-food framework: L-glutamine is a conventional amino-acid ingredient, not a novel food, but health-claim use is restricted (EFSA has not authorised glutamine sports/immune claims) - European Commission / EFSA

1. Which of these standards and regulation hold for the sense of L-glutamine this model covers, and on what evidence? provenance

Real-world use

Reported by the breadth pass; each item needs checking against its source before it becomes normative.

• Endogenous proteinogenic amino acid: incorporated into proteins; also the most abundant free amino acid in human plasma and skeletal muscle, used to shuttle nitrogen (as the amide) between tissues.
• Clinical medicine: oral L-glutamine powder (Endari) to reduce sickle-cell acute complications (pain crises, acute chest, hospitalisations) in patients ≥5 years.
• Clinical nutrition: supplied in parenteral nutrition almost always as the dipeptide L-alanyl-L-glutamine (not free L-glutamine) to support intestinal mucosa and immune cells in catabolic patients; also used in some enteral formulas.
• Dietary supplements / sports nutrition: bulk powder or capsules marketed for recovery, gut integrity, and immune support; evidence for healthy athletes is mixed and EU health claims are not authorised.
• Biopharmaceutical manufacturing and research: essential (or 'essential in culture') amino acid in mammalian cell-culture media (CHO, HEK); consumed rapidly and degrades to pyroglutamate and ammonia, so often replaced by alanyl-glutamine or glycyl-glutamine dipeptides.
• Chemical / diagnostic: chiral building block; 13C/15N-L-glutamine used as a metabolic tracer in cancer and immunology research (glutaminolysis).
• Food processing: minor direct food use as an amino acid; related enzyme glutaminase / glutamine transglutaminase uses are about other reagents, not bulk L-glutamine as the food itself.

1. Which of these real-world use hold for the sense of L-glutamine this model covers, and on what evidence? provenance

Typical measurements

Reported by the breadth pass; each item needs checking against its source before it becomes normative.

• Molecular mass (anhydrous) - 146.14 - g·mol⁻¹
• Specific optical rotation [α]D (pharmacopeial identity of the L-enantiomer) - about +6.3 to +7.3 (c = 4, in water; confirm monograph conditions) - ° (degrees)
• Aqueous solubility (20-25 °C) - roughly 25-45 - g·L⁻¹
• Human fasting plasma L-glutamine - about 500-800 (typically ~600) - µmol·L⁻¹
• Skeletal-muscle free glutamine (intracellular) - about 20 - mmol·kg⁻¹ wet weight (order of magnitude)
• Oral pharmaceutical dose (sickle cell, Endari) - 5-15 g twice daily, weight-banded (10-65 kg+) - g·day⁻¹ (as two divided doses)
• Supplement serving (sports/gut products) - 5-10 per serving; 5-30 total - g·day⁻¹
• Cell-culture media concentration (free L-glutamine) - 2-4 (often 2) - mmol·L⁻¹
• Assay (USP/FCC) - 98.0-101.0 (dried basis, typical amino-acid monograph window) - % w/w
• Isoelectric point (pI) - about 5.65 - pH units

1. Which of these typical measurements hold for the sense of L-glutamine this model covers, and on what evidence? provenance

Failure modes and hazards

Reported by the breadth pass; each item needs checking against its source before it becomes normative.

• Chemical instability in water: cyclises to pyroglutamic acid (5-oxoproline) and releases ammonia, especially with heat, time, and non-neutral pH - the reason free glutamine is omitted from heat-sterilised PN bags.
• Ammonia load: degradation in media or in vivo deamidation (glutaminase) produces NH3/NH4+, toxic to cells in culture and a concern in hepatic encephalopathy.
• Clinical inefficacy / over-claim: sports and 'immune booster' uses often fail to show benefit in well-fed athletes; marketing claims can outrun evidence.
• GI adverse effects at high oral doses: nausea, vomiting, abdominal pain, constipation or gas (seen in the Endari trials and in supplement use).
• Drug-disease caution: extra nitrogen/glutamate-glutamine flux is used carefully in severe hepatic disease; glutamine is a preferred fuel of some cancers (glutaminolysis), which complicates high-dose use in oncology (still investigational).
• Confusion with MSG / free glutamate: oral glutamine is not the same exposure as monosodium glutamate, but both sit on the glutamate-glutamine axis and are mixed up in public discussion.
• Powder handling: hygroscopic caking; microbial contamination of bulk amino-acid powders if poorly stored; not a high-potency toxin but pharmaceutical grades require endotoxin/bioburden control.
• D-glutamine or racemate substitution: wrong stereoisomer is not proteinogenic in humans and would fail pharmacopeial optical-rotation tests.

1. Which of these failure modes and hazards hold for the sense of L-glutamine this model covers, and on what evidence? provenance

Regional variation

Reported by the breadth pass; each item needs checking against its source before it becomes normative.

• United States: L-glutamine exists both as an FDA-approved drug (Endari for sickle cell) and as a widely sold dietary supplement; the same molecule, different legal pathways and labeling.
• European Union: no authorised EFSA health claims for glutamine in foods/supplements; parenteral glutamine is typically the dipeptide (Dipeptiven and generics), not free L-glutamine in the bag.
• Japan / East Asia: L-glutamine has a longer clinical-nutrition and GI-mucosal tradition (e.g. hospital enteral use, some OTCs); food-additive and pharma grades follow JP (Japanese Pharmacopoeia) as well as USP/Ph. Eur.
• Sports-nutrition markets (US, Brazil, UK): high visibility as a recovery powder; in the EU the same products cannot carry immune or muscle claims.
• Naming: 'glutamine' in clinical PN almost always means alanyl-glutamine dipeptide; in gym supplements it means free L-glutamine powder; in biochemistry it may mean the residue Gln/Q.
• Sickle-cell indication is a US (and some other) regulatory approval, not a universal standard of care worldwide.

1. Which of these regional variation hold for the sense of L-glutamine this model covers, and on what evidence? provenance

Neighbouring kinds and how to tell them apart

Reported by the breadth pass; each item needs checking against its source before it becomes normative.

• D-glutamine - Mirror-image enantiomer (CAS 5959-95-5). Separate by specific optical rotation (L is dextrorotatory under USP conditions) or chiral HPLC; only L is proteinogenic in animals.
• DL-glutamine (racemate) - Equimolar L+D (CAS 6899-04-3). Optical rotation ~0; pharmacopeial [α]D and chiral chromatography distinguish it from L.
• L-glutamic acid / glutamate (Glu, E) - Same carbon skeleton but a free γ-carboxylate instead of the carboxamide. Ninhydrin/HPLC amino-acid analysis, mass (147.13 vs 146.14), and side-chain pKa; glutamate is an excitatory neurotransmitter and the residue after glutaminase action.
• Monosodium glutamate (MSG) - Sodium salt of L-glutamic acid used as a flavour enhancer (E621), not the amide. Label, sodium content, and IR/NMR of carboxylate vs amide; MSG is not a glutamine supplement.
• L-alanyl-L-glutamine (and glycyl-L-glutamine) dipeptides - Heat-stable PN/media forms that release glutamine after hydrolysis. Different MW (217 vs 146), peptide bond in NMR/MS, and labeled as dipeptide APIs (e.g. Dipeptiven), not 'L-glutamine USP'.
• Pyroglutamic acid (5-oxoproline) - Cyclisation/degradation product of glutamine (and also of glutathione metabolism). No primary amine of an α-amino acid in the same way; appears as a related-substance peak in stability studies.
• Asparagine (L-Asn) - Homologous shorter amide (C4 vs C5). Amino-acid analyser retention time and mass (132.12 vs 146.14); both are amide amino acids but Asn is encoded by AAY and is not the main plasma nitrogen shuttle.
• Glutaminase / glutamine synthetase (enzymes) and gluten - Name-neighbours only. Enzymes are proteins that make or break glutamine; gluten is a wheat storage-protein mixture. Identity is by CAS/InChI of the small molecule versus protein/foodstuff class.

1. Which of these neighbouring kinds and how to tell them apart hold for the sense of L-glutamine this model covers, and on what evidence? provenance