L-histidine
Enable an AI agent to identify L-histidine, assess the condition and suitability of a material containing it, and determine which handling or use actions are supported by evidence.
Research draft, second pass
A second pass drafted this model: the structure a model of this thing needs, and what is known about it in the world. The line under this one says how the second half was obtained - researched against sources, or recalled without web access, in which case nothing here was read anywhere and every claim is a lead to verify. Unreviewed either way.
Researched by: Codex + Grok
Purpose and description
Enable an AI agent to identify L-histidine, assess the condition and suitability of a material containing it, and determine which handling or use actions are supported by evidence.
L-histidine is the genetically encoded S-2-amino-3-(1H-imidazol-4-yl)propanoic acid whose side-chain imidazole (pKa ≈ 6) supplies proteins with pH-dependent acid-base catalysis and metal coordination, and which humans must obtain from the diet as the precursor of histamine, carnosine and urocanate.
It can be Compare identity and chiral-analysis evidence with the L-histidine reference identity.; Calculate a preparation quantity from assay, water content and supplied-form composition.; Assess whether a specified solvent, concentration and pH support the intended dissolved state.; Evaluate measured buffering or metal-association behaviour for a named formulation.; Assign a lot to a specified use, quarantine it or request further testing against documented criteria.; Track dissolution, pH adjustment and covalent transformation while preserving links between starting material and resulting species..
Distinguishing features
Match molecular connectivity to the histidine alpha-amino-acid structure with an imidazole side chain; formula C6H9N3O2 alone does not establish identity. [PubChem L-Histidine](https://pubchem.ncbi.nlm.nih.gov/compound/L-Histidine)
Establish the L configuration, corresponding to the 2S stereocentre, using stereospecific evidence; an achiral identity assay cannot distinguish the D enantiomer. [PubChem L-Histidine](https://pubchem.ncbi.nlm.nih.gov/compound/L-Histidine)
Check counterions and water content before treating a supplied histidine salt or hydrate as the parent material for mass calculations.
Resolve free L-histidine from peptide-bound histidine and covalently modified derivatives; a result obtained after hydrolysis does not establish the original free fraction.
Verify the amino-acid carboxyl group and overall connectivity when excluding histamine or other imidazole-containing compounds.
Scope
+ Identification of free L-histidine and verification of its stereochemistry
+ L-histidine content and impurities in identified material lots or samples
+ Solid, dissolved and protonation states under recorded conditions
+ Relationships to salt forms, hydrates and metal-associated species
+ Evidence supporting storage, preparation and suitability for a specified use
- D-histidine and DL-histidine as independently identified substances
- Histamine and other covalent transformation products
- Histidine residues within peptides, proteins and affinity tags
- Complete formulations, culture media and finished supplements
- Organism-level histidine metabolism, nutritional requirements and clinical treatment
- Manufacturing equipment and laboratory procedures as independently managed things
Characteristics
- Identity evidence
- Sample linked to reference structure, reference material, method and identification result A histidine label or identifier alone does not demonstrate that the sampled material is L-histidine.
- Enantiomeric composition
- L and D mole fractions or enantiomeric excess in %, with method and quantitation limits Separates stereochemical purity from total histidine assay.
- Supplied chemical form
- Parent L-histidine; identified salt or hydrate; mixture; unresolved Controls identity boundaries and conversion between supplied mass and L-histidine amount.
- L-histidine assay
- % by mass or mg/g, specifying as-is, dry or parent-equivalent basis Supports preparation calculations without confusing assay basis, water content and counterion mass.
- Water content
- % by mass, with analytical method Affects mass-based preparation and interpretation of a claimed hydrate or dry-basis assay.
- Physical presentation
- Solid; fully dissolved; partially dissolved; suspension; precipitated; unknown Determines whether sampling and transfer can deliver a representative amount.
- Solution environment
- Linked solvent composition, pH, temperature in °C and ionic composition Makes observations of protonation, dissolution and buffering interpretable.
- Dissolved L-histidine concentration
- mol/L or g/L, with volume temperature and chemical-form basis Distinguishes the dissolved amount from material merely added to a preparation.
- Protonation assignment
- Assigned ionic species or distribution; measured, calculated or unresolved Supports interpretation of acid-base behaviour without changing the underlying L-histidine identity.
- Impurity profile
- Analyte-specific mg/kg, mol%, or relevant biological count, with detection limits Makes suitability depend on impurities relevant to the intended application.
- Use disposition
- Unassessed; accepted for named use; restricted; quarantined; rejected Prevents an analytical-grade or high-assay material from being assumed suitable for every application.
Where this came from
wikidata · CC0 1.0
Drafted structure
Bundle to layer to finding to question, as the second pass will find it: 6 bundles · 12 layers · 19 findings · 30 questions.
Histidine identity Evidence that the material has the intended molecular structure and L stereochemistry.
Histidine names and non-chiral assays can conceal differences that change whether this registry entry applies.
Molecular connectivity
Recognition of the free histidine molecule.
Free histidine identification
Record evidence distinguishing free histidine from imidazole-containing neighbours and covalently bound residues.
- Which structural reference and analytical observations identify the sample as free histidine? definition
- Was histidine measured directly or released from another substance during sample preparation? boundary
L stereochemistry
Verification of configuration and enantiomeric composition.
Enantiomer verification
Record stereospecific evidence separately from total histidine content.
- Which method and reference establish the L configuration and quantify any D-histidine? measurement
- What enantiomeric acceptance criterion applies to the intended use, and is the method sensitive enough to evaluate it? action
Material form and amount The supplied form and the amount of L-histidine that it represents.
Counterions, water and assay conventions can make equal weighed masses deliver different amounts of L-histidine.
Parent and associated forms
Classification of parent material, salts, hydrates and mixtures.
Supplied form resolution
Record the actual supplied form and its relationship to the parent registry identity.
- Is the material parent L-histidine, an identified salt or hydrate, or a mixture containing it? boundary
- What measurements or supplier evidence establish counterion identity, stoichiometry and water content? provenance
Assay and equivalents
Interpretation of assay values and preparation quantities.
Available histidine amount
Express the amount of L-histidine on an explicit and reproducible basis.
- Does the reported assay measure L-histidine specifically or total histidine, and on what mass basis? measurement
- What supplied mass provides the required L-histidine amount after accounting for assay, chemical form and water without double correction? action
Solution and acid-base state Dissolution and ionic-state evidence under specified preparation conditions.
A named concentration or pH is insufficient unless the material is dissolved and its chemical environment is recorded.
Dissolution state
The distinction between added, dissolved and precipitated L-histidine.
Dissolved fraction
Record whether the intended amount is present in the sampled liquid phase.
- At the recorded solvent composition, temperature and pH, what evidence establishes complete dissolution or a remaining solid fraction? measurement
- Could dilution, cooling or pH adjustment change the dissolved fraction before the planned use? action
Protonation and buffering
Condition-dependent acid-base behaviour of the histidine functional groups.
Ionic state evidence
Record measured or inferred protonation behaviour without assigning universal values to every environment.
- Which pH measurement and condition-specific acid-base evidence support the assigned protonation distribution? measurement
- If buffering is intended, what measured capacity and acceptable pH interval support the proposed formulation? action
Interactions and transformations Interactions and reactions that affect available L-histidine or produce a different substance.
Association, incorporation and conversion must not be mistaken for an unchanged amount of free L-histidine.
Metal and matrix association
Assessment of associated and analytically available fractions in the actual matrix.
Association-dependent availability
Record evidence for interactions relevant to the intended measurement or use.
- Which metals or matrix components are present, and what evidence establishes an associated L-histidine fraction under these conditions? measurement
- Does the intended use require total dissolved histidine or a specifically unassociated fraction? boundary
Covalent change
Recognition of reactions that cross the free L-histidine identity boundary.
Reaction product boundary
Track consumption of L-histidine and link products to their own identities.
- What analytical evidence indicates conversion to histamine, a covalent derivative or a peptide-bound residue? measurement
- Which resulting species require separate model links, and how much free L-histidine remains? boundary
Lot quality and use readiness Lot-specific evidence supporting a defined handling, preparation or application decision.
L-histidine identity and bulk assay do not establish impurity acceptability, storage validity or suitability for a particular use.
Quality evidence
Traceable analytical results and application-specific acceptance criteria.
Lot acceptance basis
Connect the sampled lot to evidence for the attributes relevant to its proposed application.
- Which lot-linked certificate and test results establish identity, enantiomeric composition, assay and relevant impurities? provenance
- Which acceptance criteria for the named use address related amino acids, residual process materials, metals or microbial quality where relevant? action
Storage and preparation history
History that can alter the reliability of recorded composition and state.
Condition validity
Record whether storage and preparation history support continued reliance on previous measurements.
- What documented conditions and retest period apply to this L-histidine form or prepared solution? provenance
- Have moisture exposure, heating, pH adjustment, precipitation or suspected contamination created a need for reassessment? action
Permitted use decision
A bounded decision about what may be done with the particular material.
Application release
Tie release, restriction or quarantine to the named application and supporting evidence.
- For which specific application do the form, concentration, impurity profile and quality documentation establish suitability? action
- Which handling instructions and unresolved evidence gaps constrain preparation, transfer or release of this material? action
Evidence and external alignment What the world already says about this thing, gathered so the model can be checked against it.
A model that cannot be lined up against existing standards, identifiers and practice cannot be adopted by anyone who already uses them.
Reported evidence
Findings from the breadth pass, kept separate from the structural claims.
Kinds and varieties
Reported by the breadth pass; each item needs checking against its source before it becomes normative.
- crystalline L-histidine free base
- L-histidine monohydrochloride monohydrate (principal commercial salt)
- pharmacopoeial / parenteral-nutrition grade
- food-chemical and feed-additive grades from fermentation
- protein-bound histidine residues (catalytic, heme-axial, zinc-site)
- oligohistidine affinity tags (His6 and variants)
- N-acetyl-L-histidine (dominant free imidazole pool in teleost lens and brain)
- stable-isotope-labelled L-histidine (13C/15N) for flux and NMR work
- Which of these kinds and varieties hold for the sense of L-histidine 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 - 71-00-1 - Free-base L-histidine; the monohydrochloride monohydrate is 5934-29-2
- Wikidata - Q485277 - Item for L-histidine; the broader histidine class is Q188017
- PubChem CID - 6274 - L-histidine
- ChEBI - CHEBI:15971 - L-histidine; generic histidine is CHEBI:27570
- UNII - 4QD397987E - FDA Substance Registration System for L-histidine
- InChIKey - HNDVDQJCIGZPNO-YFKPBYRVSA-N - Stereospecific key; the YFKPBYRV infix marks the L (S) enantiomer
- EC / EINECS - 200-745-3 - Inventory listing for L-histidine
- IUBMB residue codes - His / H - Three-letter and one-letter amino-acid codes
- KEGG Compound - C00135 - L-Histidine in metabolic maps
- HMDB - HMDB0000177 - Human metabolome entry for L-histidine
- Which of these identifiers and schemes hold for the sense of L-histidine 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 - Histidine and Histidine Hydrochloride Monohydrate monographs (USP-NF, U.S. Pharmacopeial Convention)
- European Pharmacopoeia - Histidine (0910) and Histidine hydrochloride monohydrate (0911) (EDQM, Council of Europe)
- Japanese Pharmacopoeia - Histidine / Histidine Hydrochloride Hydrate (PMDA / MHLW)
- Food Chemicals Codex - L-Histidine (U.S. Pharmacopeial Convention)
- 21 CFR 172.320 Amino acids - permits listed L-amino acids, including L-histidine, as nutrients in food (U.S. FDA)
- Regulation (EC) No 1831/2003 on additives for use in animal nutrition, plus implementing regulations authorising L-histidine monohydrochloride monohydrate from named fermentation strains (European Commission)
- Codex Alimentarius CXS 72-1981 Standard for Infant Formula - sets a minimum histidine content in the amino-acid profile (Codex Alimentarius Commission, FAO/WHO)
- Commission Delegated Regulation (EU) 2016/127 - infant-formula composition, including indispensable amino acids (European Commission)
- WHO/FAO/UNU 2007 amino-acid scoring pattern - histidine treated as indispensable at 10 mg/kg/day and 15 mg/g protein (WHO, FAO, UNU)
- Directive 2002/46/EC on food supplements - amino acids allowed in supplements subject to national positive lists (European Parliament and Council)
- Which of these standards and regulation hold for the sense of L-histidine 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.
- Indispensable amino acid in mixed diets, medical foods and crystalline amino-acid parenteral-nutrition solutions, especially for infants
- pH ~6 buffering excipient in monoclonal-antibody and other biologic drug products
- Hexahistidine tags for immobilised-metal affinity chromatography (Ni/Co IMAC) of recombinant proteins
- Metabolic precursor of histamine (histidine decarboxylase), carnosine/anserine and trans-urocanate (histidine ammonia-lyase)
- Fortification of infant formula and some animal feeds (poultry, pigs, salmonids) as a fermentation product
- Coordination of heme iron in hemoglobin and myoglobin (proximal and distal histidine) and of zinc in zinc-finger and catalytic sites
- Free histidine in scombroid fish muscle as the substrate that spoilage bacteria convert to histamine
- Research reagent and internal standard in amino-acid analysis, metabolomics and 13C/15N tracer studies
- Which of these real-world use hold for the sense of L-histidine 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 (free base) - 155.15 (monoisotopic 155.0695) - g·mol−1
- imidazole side-chain pKa - 5.9-6.1 - pKa
- isoelectric point - 7.47-7.59 - pH
- specific optical rotation [α]D in 6 M HCl - +11.5 to +13.5 - deg·mL·g−1·dm−1
- aqueous solubility at 25 °C - 38-46 - g·L−1
- adult dietary requirement (WHO/FAO/UNU 2007) - ~10 - mg·kg−1·day−1
- fasting plasma free histidine (adults) - 70-120 - µmol·L−1
- nitrogen mass fraction (C6H9N3O2) - 27.1 - % w/w
- Which of these typical measurements hold for the sense of L-histidine 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.
- Bacterial decarboxylation of free histidine in tuna, mackerel and related fish to histamine (scombroid/histamine fish poisoning)
- Photo-oxidation and metal-catalysed oxidation of protein histidine to 2-oxo-histidine in stressed biologics
- Histidinemia from histidine ammonia-lyase (HAL) deficiency, usually a benign hyperaminoacidemia
- High-dose free histidine can chelate zinc and copper and disturb trace-metal balance
- Omission or under-dosing in infant parenteral nutrition, where histidine is strictly indispensable
- Alkaline or thermal racemisation to D-histidine during harsh hydrolysis or processing
- pH drift, buffer crystallisation or freeze-thaw instability in histidine-buffered antibody formulations
- Nickel leaching and residual His-tag immunogenicity from IMAC purification
- Which of these failure modes and hazards hold for the sense of L-histidine 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.
- Older U.S. nutrition texts often called histidine 'semi-essential' in adults; WHO/FAO/UNU 2007 lists it as indispensable at 10 mg/kg/day
- EU authorises named fermentation organisms as feed additives under 1831/2003; the U.S. treats food use under 21 CFR 172.320 and feed use largely via AAFCO ingredient definitions
- Japan sells histidine-rich skipjack (katsuo) extracts as anti-fatigue Foods with Function Claims; that food-use framing is uncommon in the EU or U.S.
- Infant-formula histidine minima differ in detail among Codex CXS 72, EU 2016/127 and U.S. 21 CFR 107
- Ph. Eur., USP and JP all split the free base from the hydrochloride monohydrate; commercial Asian feed product is almost always the monohydrate salt
- Which of these regional variation hold for the sense of L-histidine 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-histidine - Opposite specific rotation and opposite elution on chiral HPLC or ligand-exchange chromatography; same elemental formula
- L-histidine monohydrochloride monohydrate - Chloride assay, water of crystallisation (~8-9% w/w), and a more acidic aqueous pH than the free base
- histamine - Decarboxylation product (C5H9N3 vs C6H9N3O2); LC-MS [M+H]+ 112 versus 156, and a positive fluorometric o-phthalaldehyde test without an α-carboxyl
- L-arginine - Guanidino side chain gives a positive Sakaguchi test; histidine's imidazole gives a Pauly (diazotised sulphanilic acid) colour and a pKa near 6 rather than ~12.5
- L-lysine - Primary-amine side chain, no imidazole; does not give the Pauly reaction and elutes differently on cation-exchange amino-acid analysis
- trans-urocanic acid - HAL deamination product; lacks the α-amino group, absorbs near 277 nm, and is ninhydrin-negative
- carnosine (β-alanyl-L-histidine) - Dipeptide mass and a second ninhydrin-reactive residue; acid hydrolysis liberates β-alanine plus histidine
- 3-methyl-L-histidine - Extra ring methyl (marker of actin/myosin turnover); separated by ion-exchange or LC-MS, not by a bulk ninhydrin assay
- Which of these neighbouring kinds and how to tell them apart hold for the sense of L-histidine this model covers, and on what evidence? provenance
Sources
- PubChem Compound Summary for CID 6274, L-Histidine - CAS, UNII, InChIKey, molecular formula/mass, and the free-base identity of L-histidine
- ChEBI: L-histidine (CHEBI:15971) - ChEBI identifier, stereochemical definition, and links to the generic histidine class versus the L-enantiomer
- Protein and amino acid requirements in human nutrition. Report of a Joint FAO/WHO/UNU Expert Consultation - Adult essentiality, the 10 mg/kg/day requirement, and the 15 mg/g protein scoring pattern for histidine
- European Pharmacopoeia monographs Histidine and Histidine hydrochloride monohydrate - Pharmacopoeial distinction of free base versus hydrochloride monohydrate, specific-rotation and identification tests
- 21 CFR 172.320 Amino acids - U.S. food-additive listing of amino acids, including L-histidine, as nutrients
- Nomenclature and symbolism for amino acids and peptides (IUPAC-IUB Joint Commission on Biochemical Nomenclature recommendations 1983) - Three-letter His / one-letter H codes and the S / L stereochemical designation
What the second pass must settle
- Does the registry already provide authoritative models for L-histidine salts, hydrates or ionic species, and where should this entry link to them?
- Which validated analytical methods and acceptance limits should establish identity, D-histidine content and related impurities for each intended grade?
- Which measured solubility, acid-base and buffering data cover the solvents, temperatures and ionic compositions relevant to actual uses?
- What stability evidence supports storage and retest limits for the supplied solid forms and prepared solutions?
- Under which application conditions do metal association or conversion products materially change the amount of usable free L-histidine?