{{short description|Chemical compound}} {{chembox | Name = Histidine | ImageFile1_Ref = {{chemboximage|correct|??}} | ImageFile1 = File:L-Histidin - L-Histidine.svg | ImageSize1 = 175 | ImageCaption1 = Structure of histidine | ImageFileL2 = Histidine-from-xtal-3D-bs-17.png | ImageSizeL2 = 125 | ImageCaptionL2 = Ball-and-stick model | ImageFileR2 = Histidine-from-xtal-3D-sf.png | ImageSizeR2 = 125 | ImageCaptionR2 = Space-filling model | IUPACName = Histidine | OtherNames = | SystematicName = 2-Amino-3-(1''H''-imidazol-4-yl)propanoic acid | Section1 = {{Chembox Identifiers | CASNo = 71-00-1 | CASNo_Ref = {{cascite|correct|CAS}} | Beilstein = 84088 | ChEMBL_Ref = {{ebicite|correct|EBI}} | ChEMBL = 17962 | ChEBI_Ref = {{ebicite|correct|EBI}} | ChEBI = 15971 | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID = 6038 | UNII_Ref = {{fdacite|correct|FDA}} | UNII = 4QD397987E | EINECS = 200-745-3 | Gmelin = 83042 | IUPHAR_ligand = 3310 | KEGG_Ref = {{keggcite|correct|kegg}} | KEGG = D00032 | SMILES = O=C([C@H](CC1=CNC=N1)N)O | SMILES1 = O=C([C@H](CC1=CNC=N1)[NH3+])[O-] | SMILES1_Comment = Zwitterion | SMILES2 = O=C([C@H](CC1=CNC=[NH1+]1)[NH3+])[O-] | SMILES2_Comment = Protonated zwitterion | StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI = 1S/C6H9N3O2/c7-5(6(10)11)1-4-2-8-3-9-4/h2-3,5H,1,7H2,(H,8,9)(H,10,11)/t5-/m0/s1 | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey = HNDVDQJCIGZPNO-YFKPBYRVSA-N | PubChem = 6274 | DrugBank_Ref = {{drugbankcite|correct|drugbank}} | DrugBank = DB00117 }} | Section2 = {{Chembox Properties | C=6 | H=9 | N=3 | O=2 | Appearance = | Density = | MeltingPt = | BoilingPt = | Solubility = 45.6mg/mL<ref>{{cite web |title=Histidine (HMDB0000177) |url=https://www.hmdb.ca/metabolites/HMDB0000177 |website=Human Metabolome Database |access-date=22 March 2025 |language=en}}</ref> }} | Section3 = {{Chembox Hazards | NFPA-H = 1 | NFPA-F = 1 | NFPA-R = 0 | MainHazards = | FlashPt = | AutoignitionPt = }} }} thumb|Histidine ball and stick model spinning '''Histidine''' or '''histidin'''<ref name="dict">{{cite web |url=https://www.dictionary.com/browse/histidine |title=Histidine |website=Dictionary.com |access-date=24 March 2026}}</ref> (symbol '''His''' or '''H''')<ref name=":7">{{cite web | url = http://www.chem.qmul.ac.uk/iupac/AminoAcid/AA1n2.html | title = Nomenclature and Symbolism for Amino Acids and Peptides | publisher = IUPAC-IUB Joint Commission on Biochemical Nomenclature | year = 1983 | access-date = 5 March 2018 | archive-url = https://web.archive.org/web/20081009023202/http://www.chem.qmul.ac.uk/iupac/AminoAcid/AA1n2.html | archive-date = 9 October 2008 }}</ref> is an essential amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated –NH<sub>3</sub><sup>+</sup> form under biological conditions), a carboxylic acid group (which is in the deprotonated –COO<sup>−</sup> form under biological conditions), and an imidazole side chain (which is partially protonated), classifying it as a positively charged amino acid at physiological pH. Initially thought essential only for infants, it has now been shown in longer-term studies to be essential for adults also.<ref>{{cite journal |doi=10.1172/JCI108016 |title=Evidence that histidine is an essential amino acid in normal and chronically uremic man |year=1975 |last1=Kopple |first1=Joel D |last2=Swendseid |first2=Marian E |journal=Journal of Clinical Investigation |volume=55 |issue=5 |pages=881–91 |pmid=1123426 |pmc=301830}}</ref> It is encoded by the codons CAU and CAC.

Histidine was first isolated by Albrecht Kossel and Sven Gustaf Hedin in 1896.<ref>{{Cite journal|last1=Vickery|first1=Hubert Bradford|last2=Leavenworth|first2=Charles S.|title=On the Separation of Histidine and Arginine|date=1928-08-01|url=http://www.jbc.org/content/78/3/627.full.pdf|journal=Journal of Biological Chemistry|language=en|volume=78|issue=3|pages=627–635|doi=10.1016/S0021-9258(18)83967-9|issn=0021-9258|doi-access=free}}</ref> The name stems from its discovery in tissue, from {{wikt-lang|grc|ἱστός}} ''histós'' "tissue".<ref name=":7" /> {{fv|date=April 2026}} It is also a precursor to histamine, a vital inflammatory agent in immune responses. The acyl radical is '''histidyl'''.

==Properties of the imidazole side chain==

At neutral or physiological pH, the imidazole side chain is neutral. The imidazole side chain in histidine has a p''K''<sub>a</sub> of approximately 6.0. Thus, below a pH of 6, the imidazole ring is mostly protonated and carries a positive +1 charge (as described by the Henderson–Hasselbalch equation). The resulting imidazolium ring bears two NH bonds and has a positive charge. The positive charge is equally distributed between both nitrogen atoms and can be represented with two equally important resonance structures. Sometimes, the symbol '''Hip''' is used for this protonated form instead of the usual His.<ref name="Kim2013" /><ref name=":5">{{Cite web |title=AMBER Histidine residues |url=http://ambermd.org/Questions/HIS.html |access-date=2022-05-12 |website=ambermd.org}}</ref><ref name="Dokainish2016">{{Cite journal |last1=Dokainish |first1=Hisham M. |last2=Kitao |first2=Akio |date=2016-08-05 |title=Computational Assignment of the Histidine Protonation State in (6-4) Photolyase Enzyme and Its Effect on the Protonation Step |journal=ACS Catalysis |language=en |volume=6 |issue=8 |pages=5500–5507 |doi=10.1021/acscatal.6b01094 |s2cid=88813605 |issn=2155-5435|doi-access=free }}</ref> Above pH 6, one of the two protons is lost. The remaining proton of the imidazole ring can reside on either nitrogen atom, giving rise to what are known as the N3-H or N1-H tautomers. In the N1-H tautomer, the NH group is nearer the backbone. These neutral tautomers, also referred to as N<sub>ε</sub> (or N<sub>τ</sub>, tau meaning ''tele'' — far) and N<sub>δ</sub> (or N<sub>π</sub>, pi meaning ''pros'' — near), are sometimes referred to with symbols '''Hie''' and '''Hid''', respectively.<ref>{{cite book |title=IUPAC Compendium of Chemical Terminology |date=2025 |publisher=International Union of Pure and Applied Chemistry |edition=5th |chapter-url=https://doi.org/10.1351/goldbook.P04890 |language=en |chapter=''pros''|doi=10.1351/goldbook.P04890 }}</ref><ref name="Kim2013">{{Cite journal |last1=Kim |first1=Meekyum Olivia |last2=Nichols |first2=Sara E. |last3=Wang |first3=Yi |last4=McCammon |first4=J. Andrew |date=March 2013 |title=Effects of histidine protonation and rotameric states on virtual screening of M. tuberculosis RmlC |journal=Journal of Computer-Aided Molecular Design |language=en |volume=27 |issue=3 |pages=235–246 |doi=10.1007/s10822-013-9643-9 |issn=0920-654X |pmc=3639364 |pmid=23579613|bibcode=2013JCAMD..27..235K }}</ref><ref name=":5" /><ref name="Dokainish2016" /> The imidazole/imidazolium ring of histidine is aromatic at all pH values.<ref>{{cite journal |doi=10.1016/S0022-2860(03)00282-5 |title=Five-membered heterocycles. Part III. Aromaticity of 1,3-imidazole in 5+n hetero-bicyclic molecules |year=2003 |last1=Mrozek |first1=Agnieszka |last2=Karolak-Wojciechowska |first2=Janina |last3=Kieć-Kononowicz |first3=Katarzyna |journal=Journal of Molecular Structure |volume=655 |issue=3 |pages=397–403 |bibcode=2003JMoSt.655..397M |url=https://ruj.uj.edu.pl/xmlui/handle/item/261742 }}</ref> Under certain conditions, all three ion-forming groups of histidine can be charged forming the histidinium cation.<ref>{{Cite journal |last1=Novikov |first1=Anton P. |last2=Safonov |first2=Alexey V. |last3=German |first3=Konstantin E. |last4=Grigoriev |first4=Mikhail S. |date=2023-12-01 |title=What kind of interactions we may get moving from zwitter to "dritter" ions: C–O⋯Re(O4) and Re–O⋯Re(O4) anion⋯anion interactions make structural difference between L-histidinium perrhenate and pertechnetate |url=https://pubs.rsc.org/en/content/articlelanding/2024/ce/d3ce01164j |journal=CrystEngComm |volume=26 |issue=1 |pages=61–69 |language=en |doi=10.1039/D3CE01164J |bibcode=2023CEG....26...61N |s2cid=265572280 |issn=1466-8033|url-access=subscription }}</ref>

The acid-base properties of the imidazole side chain are relevant to the catalytic mechanism of many enzymes.<ref name="Ingle2011">{{Cite journal|last=Ingle|first=Robert A.|title=Histidine Biosynthesis|journal=The Arabidopsis Book|volume=9|article-number=e0141|doi=10.1199/tab.0141|pmc=3266711|pmid=22303266|year=2011}}</ref> In catalytic triads, the basic nitrogen of histidine abstracts a proton from serine, threonine, or cysteine to activate it as a nucleophile. In a histidine proton shuttle, histidine is used to quickly shuttle protons. It can do this by abstracting a proton with its basic nitrogen to make a positively charged intermediate and then use another molecule, a buffer, to extract the proton from its acidic nitrogen. In carbonic anhydrases, a histidine proton shuttle is utilized to rapidly shuttle protons away from a zinc-bound water molecule to quickly regenerate the active form of the enzyme. In helices E and F of hemoglobin, histidine influences binding of dioxygen as well as carbon monoxide. This interaction enhances the affinity of Fe(II) for O<sub>2</sub> but destabilizes the binding of CO, which binds only 200 times stronger in hemoglobin, compared to 20,000 times stronger in free heme.

The tautomerism and acid-base properties of the imidazole side chain has been characterized by <sup>15</sup>N NMR spectroscopy. The two <sup>15</sup>N chemical shifts are similar (about 200 ppm, relative to nitric acid on the sigma scale, on which increased shielding corresponds to increased chemical shift). NMR spectral measurements shows that the chemical shift of N1-H drops slightly, whereas the chemical shift of N3-H drops considerably (about 190 vs. 145 ppm). This change indicates that the N1-H tautomer is preferred, possibly due to hydrogen bonding to the neighboring ammonium. The shielding at N3 is substantially reduced due to the second-order paramagnetic effect, which involves a symmetry-allowed interaction between the nitrogen lone pair and the excited π* states of the aromatic ring. At pH > 9, the chemical shifts of N1 and N3 are approximately 185 and 170 ppm.<ref>{{cite book|title=ABCs of FT-NMR|last=Roberts|first=John D.|publisher=University Science Books|year=2000|isbn=978-1-891389-18-4|location=Sausalito, CA|pages=258–9}}</ref>

===Ligand=== [[Image:Succinate Dehygrogenase 1YQ3 Haem group.png|thumb|left|The histidine-bound heme group of succinate dehydrogenase, an electron carrier in the mitochondrial electron transfer chain. The large semi-transparent sphere indicates the location of the iron ion. From {{PDB|1YQ3}}.|205x205px]] [[Image:Cu3Im8laccase.png|thumb|left|The tricopper site found in many laccases. Notice that each copper center is bound to the imidazole sidechains of histidine (color code: copper is brown, nitrogen is blue).]] Histidine forms complexes with many metal ions. The imidazole sidechain of the histidine residue commonly serves as a ligand in metalloproteins. One example is the axial base attached to Fe in myoglobin and hemoglobin. Poly-histidine tags (of six or more consecutive H residues) are utilized for protein purification by binding to columns with nickel or cobalt, with micromolar affinity.<ref>{{Cite book|last1=Bornhorst|first1=J. A.|last2=Falke|first2=J. J.|chapter=Purification of proteins using polyhistidine affinity tags |date=2000|title=Applications of Chimeric Genes and Hybrid Proteins Part A: Gene Expression and Protein Purification|series=Methods in Enzymology|volume=326|pages=245–254|doi=10.1016/s0076-6879(00)26058-8|issn=0076-6879|pmc=2909483|pmid=11036646|isbn=978-0-12-182227-9 }}</ref> Natural poly-histidine peptides, found in the venom of the viper ''Atheris squamigera'' have been shown to bind Zn(II), Ni(II) and Cu(II) and affect the function of venom metalloproteases.<ref>{{Cite journal|last1=Watly|first1=Joanna|last2=Simonovsky|first2=Eyal|last3=Barbosa|first3=Nuno|last4=Spodzieja|first4=Marta|last5=Wieczorek|first5=Robert|last6=Rodziewicz-Motowidlo|first6=Sylwia|last7=Miller|first7=Yifat|last8=Kozlowski|first8=Henryk|date=2015-08-17|title=African Viper Poly-His Tag Peptide Fragment Efficiently Binds Metal Ions and Is Folded into an α-Helical Structure|journal=Inorganic Chemistry|volume=54|issue=16|pages=7692–7702|doi=10.1021/acs.inorgchem.5b01029|issn=1520-510X|pmid=26214303}}</ref>

N-terminal histidines are known to function as bidentate ligands, with a metal (generally copper) bound to both the amine of the N-terminus and the N<sub>δ</sub> of the histidine; the N<sub>ε</sub> is often methylated.<ref name="Walton2023">{{Cite journal |last1=Walton |first1=Paul H. |last2=Davies |first2=Gideon J. |last3=Diaz |first3=Daniel E. |last4=Franco-Cairo |first4=João P. |date=2023 |title=The histidine brace: nature's copper alternative to haem? |journal=FEBS Letters |language=en |volume=597 |issue=4 |pages=485–494 |doi=10.1002/1873-3468.14579 |issn=1873-3468 |pmc=10952591 |pmid=36660911}}</ref> Although recently discovered,<ref>{{Cite journal |last1=Quinlan |first1=R. Jason |last2=Sweeney |first2=Matt D. |last3=Lo Leggio |first3=Leila |last4=Otten |first4=Harm |last5=Poulsen |first5=Jens-Christian N. |last6=Johansen |first6=Katja Salomon |last7=Krogh |first7=Kristian B. R. M. |last8=Jørgensen |first8=Christian Isak |last9=Tovborg |first9=Morten |last10=Anthonsen |first10=Annika |last11=Tryfona |first11=Theodora |last12=Walter |first12=Clive P. |last13=Dupree |first13=Paul |last14=Xu |first14=Feng |last15=Davies |first15=Gideon J. |date=2011-09-13 |title=Insights into the oxidative degradation of cellulose by a copper metalloenzyme that exploits biomass components |journal=Proceedings of the National Academy of Sciences |volume=108 |issue=37 |pages=15079–15084 |doi=10.1073/pnas.1105776108 |doi-access=free |pmc=3174640 |pmid=21876164 |bibcode=2011PNAS..10815079Q }}</ref> this "histidine brace" motif is critical in biogeochemical cycles: it functions as the active site of lytic polysaccharide monooxygenases (LPMOs), which break down unreactive polysaccharides such as cellulose.<ref>{{Cite journal |last1=Munzone |first1=Alessia |last2=Eijsink |first2=Vincent G. H. |last3=Berrin |first3=Jean-Guy |last4=Bissaro |first4=Bastien |date=February 2024 |title=Expanding the catalytic landscape of metalloenzymes with lytic polysaccharide monooxygenases |url=https://www.nature.com/articles/s41570-023-00565-z |journal=Nature Reviews Chemistry |language=en |volume=8 |issue=2 |pages=106–119 |doi=10.1038/s41570-023-00565-z |pmid=38200220 |issn=2397-3358|url-access=subscription }}</ref> It is proposed that the evolution of these enzymes in fungi corresponds to the first widespread ability to decompose woody plant mass, leading to the end of the Carboniferous era and its mass accumulation of coal deposits.<ref name="Walton2023" />

==Metabolism==

=== Biosynthesis === thumb|775x775px|'''Histidine Biosynthesis Pathway''' Eight different enzymes can catalyze ten reactions. In this image, His4 catalyzes four different reactions in the pathway. {{sm|l}}-Histidine is an essential amino acid that is not synthesized ''de novo'' in humans.<ref>{{cite journal |last1=Moro |first1=Joanna |last2=Tomé |first2=Daniel |last3=Schmidely |first3=Philippe |last4=Demersay |first4=Tristan-Chalvon |last5=Azzout-Marniche |first5=Dalila |title=Histidine: A Systematic Review on Metabolism and Physiological Effects in Human and Different Animal Species |journal=Nutrients |date=14 May 2020 |volume=12 |issue=5 |page=1414 |doi=10.3390/nu12051414 |doi-access=free|pmid=32423010 |pmc=7284872 }}</ref> Humans and other animals must ingest histidine or histidine-containing proteins. The biosynthesis of histidine has been widely studied in prokaryotes such as ''E. coli''. Histidine synthesis in ''E.&nbsp;coli'' involves eight gene products (His1, 2, 3, 4, 5, 6, 7, and 8) and it occurs in ten steps. This is possible because a single gene product has the ability to catalyze more than one reaction. For example, as shown in the pathway, His4 catalyzes four different steps in the pathway.<ref name="Alifano1996">{{Cite journal|last1=Alifano|first1=P|last2=Fani|first2=R|last3=Liò|first3=P|last4=Lazcano|first4=A|last5=Bazzicalupo|first5=M|last6=Carlomagno|first6=M S|last7=Bruni|first7=C B|date=1996-03-01|title=Histidine biosynthetic pathway and genes: structure, regulation, and evolution.|journal=Microbiological Reviews|volume=60|issue=1|pages=44–69|issn=0146-0749|pmc=239417|pmid=8852895|doi=10.1128/MMBR.60.1.44-69.1996}}</ref>

Histidine is synthesized from phosphoribosyl pyrophosphate (PRPP), which is made from ribose-5-phosphate by ribose-phosphate diphosphokinase in the pentose phosphate pathway. The first reaction of histidine biosynthesis is the condensation of PRPP and adenosine triphosphate (ATP) by the enzyme ATP-phosphoribosyl transferase. ATP-phosphoribosyl transferase is indicated by His1 in the image.<ref name="Alifano1996" /> His4 gene product then hydrolyzes the product of the condensation, phosphoribosyl-ATP, producing phosphoribosyl-AMP (PRAMP), which is an irreversible step. His4 then catalyzes the formation of phosphoribosylformiminoAICAR-phosphate, which is then converted to phosphoribulosylformimino-AICAR-P by the His6 gene product.<ref name="Kulis-Horn2014">{{Cite journal|last1=Kulis-Horn|first1=Robert K|last2=Persicke|first2=Marcus|last3=Kalinowski|first3=Jörn|date=2014-01-01|title=Histidine biosynthesis, its regulation and biotechnological application in Corynebacterium glutamicum|journal=Microbial Biotechnology|volume=7|issue=1|pages=5–25|doi=10.1111/1751-7915.12055|issn=1751-7915|pmc=3896937|pmid=23617600}}</ref> His7 splits phosphoribulosylformimino-AICAR-P to form {{sm|d}}-erythro-imidazole-glycerol-phosphate. After, His3 forms imidazole acetol-phosphate releasing water. His5 then makes {{sm|l}}-histidinol-phosphate, which is then hydrolyzed by His2 making histidinol. His4 catalyzes the oxidation of {{sm|l}}-histidinol to form {{sm|l}}-histidinal, an amino aldehyde. In the last step, {{sm|l}}-histidinal is converted to {{sm|l}}-histidine.<ref name="Kulis-Horn2014" /><ref>{{Cite journal|last=Adams|first=E.|date=1955-11-01|title=L-Histidinal, a biosynthetic precursor of histidine|journal=The Journal of Biological Chemistry|volume=217|issue=1|pages=325–344|doi=10.1016/S0021-9258(19)57184-8|issn=0021-9258|pmid=13271397|doi-access=free}}</ref>

The histidine biosynthesis pathway has been studied in the fungus ''Neurospora crassa'', and a gene (''His-3'') encoding a multienzyme complex was found that was similar to the ''His4'' gene of the bacterium ''E.&nbsp;coli''.<ref name="Ahmed1968">Ahmed A. Organization of the histidine-3 region of Neurospora. Mol Gen Genet. 1968;103(2):185-93. doi: 10.1007/BF00427145. PMID 4306011</ref> A genetic study of ''N.&nbsp;crassa'' histidine mutants indicated that the individual activities of the multienzyme complex occur in discrete, contiguous sections of the ''His-3'' genetic map, suggesting that the different activities of the multienzyme complex are encoded separately from each other.<ref name = Ahmed1968/> However, mutants were also found that lacked all three activities simultaneously, suggesting that some mutations cause loss of function of the complex as a whole.

Like animals and microorganisms, plants need histidine for their growth and development.<ref name="Ingle2011" /> But unlike animals, microorganisms and plants can synthesize histidine.<ref>{{cite web |last=DeNofrio |first=Jan |url=https://www.thetech.org/ask-a-geneticist/articles/2011/ask396/ |title=How come plants can make essential amino acids but people can't? |website=The Tech Interactive |series=Ask a Geneticist |date=2011-02-08 |access-date=2024-08-04}}</ref> Both synthesize histidine from the biochemical intermediate phosphoribosyl pyrophosphate. In general, the histidine biosynthesis is very similar in plants and microorganisms.<ref>{{Cite journal|last1=Stepansky|first1=A.|last2=Leustek|first2=T.|date=2006-03-01|title=Histidine biosynthesis in plants|journal=Amino Acids|volume=30|issue=2|pages=127–142|doi=10.1007/s00726-005-0247-0|issn=0939-4451|pmid=16547652|s2cid=23733445}}</ref>

==== Regulation of biosynthesis ==== This pathway requires energy in order to occur; therefore, the presence of ATP activates the first enzyme of the pathway, ATP-phosphoribosyl transferase (shown as His1 in the image on the right). ATP-phosphoribosyl transferase is the rate determining enzyme, which is regulated through feedback inhibition, meaning that it is inhibited in the presence of the product, histidine.<ref>{{Cite journal|last1=Cheng|first1=Yongsong|last2=Zhou|first2=Yunjiao|last3=Yang|first3=Lei|last4=Zhang|first4=Chenglin|last5=Xu|first5=Qingyang|last6=Xie|first6=Xixian|last7=Chen|first7=Ning|date=2013-05-01|title=Modification of histidine biosynthesis pathway genes and the impact on production of L-histidine in ''Corynebacterium glutamicum''|journal=Biotechnology Letters|volume=35|issue=5|pages=735–741|doi=10.1007/s10529-013-1138-1|issn=1573-6776|pmid=23355034|s2cid=18380727}}</ref>

=== Degradation === Histidine can be metabolized into glutamate, which is readily metabolized into AKG (alpha-ketoglutarate), making histidine one of the amino acids whose metabolites can become citric acid cycle intermediates.<ref name="Swanson2010">{{cite book |last1=Swanson |first1=Todd A. |last2=Kim |first2=Sandra I. |last3=Glucksman |first3=Marc J. |last4=Lieberman |first4=Michael |last5=Swanson |first5=Todd A. |title=Biochemistry, molecular biology, and genetics |date=2010 |publisher=Wolters Kluwer Health/Lippincott Williams & Wilkins |location=Philadelphia |isbn=978-0-7817-9875-4 |edition=5th}}{{Page needed|date=March 2025}}</ref> The process requires several steps. In prokaryotes, histidine first undergoes deamination, the removal of its amino group by the emzyme histidase. This step produces ammonia and urocanic acid (urocanate).<ref>{{Cite journal|last1=Mehler|first1=A. H.|last2=Tabor|first2=H.|date=1953-04-01|title=Deamination of histidine to form urocanic acid in liver|journal=The Journal of Biological Chemistry|volume=201|issue=2|pages=775–784|doi=10.1016/S0021-9258(18)66234-9|issn=0021-9258|pmid=13061415|doi-access=free}}</ref> The enzyme urocanase then converts urocanic acid into imidazolonepropionate (4-imidazolone-5-propionate). The enzyme imidazolonepropionase then converts imidazolonepropionate into formiminoglutamate (FIGLU).<ref>{{Cite journal|last1=Coote|first1=J. G.|last2=Hassall|first2=H.|date=1973-03-01|title=The degradation of l-histidine, imidazolyl-l-lactate and imidazolylpropionate by Pseudomonas testosteroni|journal=Biochemical Journal|volume=132|issue=3|pages=409–422|issn=0264-6021|pmc=1177604|pmid=4146796|doi=10.1042/bj1320409}}</ref> The enzyme formimidoyltransferase cyclodeaminase removes the formimino group (which is transferred to tetrahydrofolate), leaving behind a glutamate molecule.<ref name="Swanson2010" /> Glutamate can then be deaminated by glutamate dehydrogenase or transaminated to form α-ketoglutarate.<ref name="Swanson2010" />

=== Conversion to other biologically active amines === * The histidine amino acid is a precursor for histamine, an amine produced in the body necessary for inflammation.<ref>{{Cite journal|last1=Andersen|first1=Hjalte H.|last2=Elberling|first2=Jesper|author-link3=Lars Arendt-Nielsen|last3=Arendt-Nielsen|first3=Lars|date=2015-09-01|title=Human surrogate models of histaminergic and non-histaminergic itch|journal=Acta Dermato-Venereologica|volume=95|issue=7|pages=771–777|doi=10.2340/00015555-2146|issn=1651-2057|pmid=26015312|url=http://vbn.aau.dk/files/219083590/4442_9.pdf|doi-access=free}}</ref> * The enzyme histidine ammonia-lyase converts histidine into ammonia and urocanic acid. A deficiency in this enzyme is present in the rare metabolic disorder histidinemia, producing urocanic aciduria as a key diagnostic finding. * Histidine can be converted to 3-methylhistidine, which serves as a biomarker for skeletal muscle damage, by certain methyltransferase enzymes.<ref name="HMDB 3-Methylhistidine">{{cite web | title=3-Methylhistidine | url=http://www.hmdb.ca/metabolites/HMDB00479 | work=HMDB Version&nbsp;4.0 | publisher=Human Metabolome Database | access-date=25 December 2017 | date=20 December 2017 }}</ref> * Histidine is also a precursor for carnosine biosynthesis, which is a dipeptide found in skeletal muscle.<ref>{{Cite journal|last1=Derave|first1=Wim|last2=Everaert|first2=Inge|last3=Beeckman|first3=Sam|last4=Baguet|first4=Audrey|date=2010-03-01|title=Muscle carnosine metabolism and beta-alanine supplementation in relation to exercise and training|journal=Sports Medicine|volume=40|issue=3|pages=247–263|doi=10.2165/11530310-000000000-00000|issn=1179-2035|pmid=20199122|hdl=1854/LU-897781|s2cid=7661250|url=https://biblio.ugent.be/publication/897781|hdl-access=free}}</ref> * In Actinomycetota and filamentous fungi, such as ''Neurospora crassa'', histidine can be converted into the antioxidant ergothioneine.<ref name="Fahey">{{cite journal |doi=10.1146/annurev.micro.55.1.333 |title=Novelthiols Ofprokaryotes |year=2001 |last1=Fahey |first1=Robert C. |journal=Annual Review of Microbiology |volume=55 |pages=333–56 |pmid=11544359}}</ref> [[File:Histidine decarboxylase.svg|thumb|center|400px|Conversion of histidine to histamine by histidine decarboxylase]]

==Requirements== The Food and Nutrition Board (FNB) of the U.S. Institute of Medicine set Recommended Dietary Allowances (RDAs) for essential amino acids in 2002. For histidine, for adults 19 years and older, 14&nbsp;mg/kg body weight/day.<ref name="DRItext">{{cite book | last1 = Institute of Medicine | title = Dietary Reference Intakes for Energy, Carbohydrates, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids | chapter = Protein and Amino Acids | publisher = The National Academies Press | year = 2002 | location = Washington, DC | pages = 589–768 | doi = 10.17226/10490 | bibcode = 2002nap..book10490I | isbn = 978-0-309-08525-0 | chapter-url = https://www.nap.edu/read/10490/chapter/12| author1-link = Institute of Medicine }}</ref> Supplemental histidine is being investigated for use in a variety of different conditions, including neurological disorders, atopic dermatitis, metabolic syndrome, diabetes, uraemic anaemia, ulcers, inflammatory bowel diseases, malignancies, and muscle performance during strenuous exercise.<ref>{{Cite journal |last=Holeček |first=Milan |date=2020-03-22 |title=Histidine in Health and Disease: Metabolism, Physiological Importance, and Use as a Supplement |journal=Nutrients |volume=12 |issue=3 |page=848 |doi=10.3390/nu12030848 |issn=2072-6643 |pmc=7146355 |pmid=32235743|doi-access=free }}</ref>

== Medical uses == Histidine’s role in skin health has attracted research interest because the amino acid is a precursor to filaggrin, a structural protein that helps maintain the integrity of the skin’s outer barrier. Filaggrin is rich in histidine and, when broken down, contributes to the natural moisturizing factor that helps retain moisture and supports barrier function. Clinical studies suggest that oral L-histidine supplementation can increase filaggrin processing and improve skin barrier function, with corresponding reductions in the severity of atopic dermatitis (eczema) compared with placebo, potentially offering a safe, nonsteroidal adjunct to traditional therapies.<ref>{{Cite journal |last1=Tan |first1=Siao Pei |last2=Brown |first2=Simon B. |last3=Griffiths |first3=Christopher Em |last4=Weller |first4=Richard B. |last5=Gibbs |first5=Neil K. |date=2017 |title=Feeding filaggrin: effects of l-histidine supplementation in atopic dermatitis |journal=Clinical, Cosmetic and Investigational Dermatology |volume=10 |pages=403–411 |doi=10.2147/CCID.S146760 |doi-access=free |issn=1178-7015 |pmc=5634381 |pmid=29042806}}</ref>

In the skincare industry, biotechnology companies such as Codex Labs<ref>{{Cite journal |last=Gibbs |first=Neil K. |date=2020-10-01 |title=l-Histidine Supplementation in Adults and Young Children with Atopic Dermatitis (Eczema) |journal=The Journal of Nutrition |volume=150 |issue=Suppl 1 |pages=2576S–2579S |doi=10.1093/jn/nxaa200 |issn=1541-6100 |pmid=33000160}}</ref>— a dermatology and firm developing skin-gut-brain-biome solutions for conditions including eczema — have incorporated histidine-containing formulations into products and supplements aimed at strengthening the skin barrier and supporting sensitive skin, reflecting growing interest in histidine’s functional importance beyond its canonical metabolic roles.<ref>{{Cite journal |last1=Nong |first1=Yvonne |last2=Gahoonia |first2=Nimrit |last3=Rizzo |first3=Julianne |last4=Burney |first4=Waqas |last5=Sivamani |first5=Raja K. |last6=Maloh |first6=Jessica |date=2023-02-13 |title=Prospective Evaluation of a Topical Botanical Skin Care Regimen on Mild to Moderate Facial and Truncal Acne and Mood |journal=Journal of Clinical Medicine |volume=12 |issue=4 |pages=1484 |doi=10.3390/jcm12041484 |doi-access=free |issn=2077-0383 |pmc=9966061 |pmid=36836020}}</ref><ref>{{Cite news |date=October 2, 2025 |title=Codex Labs Introduces the BIA Skin Barrier Support Supplement for Eczema-Prone Infants, Toddlers and Kids under 12 |url=https://finance.yahoo.com/news/codex-labs-introduces-bia-skin-150000242.html?guce_referrer=aHR0cHM6Ly93d3cuZ29vZ2xlLmNvbS8&guce_referrer_sig=AQAAAGGO77221Hjb3U92dRo83TvmIaGxaLn0Fmqg1D9rEMVx1zYZ6Od5mVyixw0Dglbbp19-pGztWVAUK1pWxBgRCKK8GxqFVtvensGiccdPmeJISqoLCKZq2uLsvM4jw2PZk3YnsfNmW0wpmrA17PLSzu1nbP-POOMLRJYbJTR7CAcd&guccounter=2 |access-date=2025-12-18}}</ref>

== See also == * Carnosinemia * Beta-Alanine * Diphthamide * Imidazole propionate * Pauly reaction

== References == {{reflist}}

== External links == *[http://gmd.mpimp-golm.mpg.de/Spectrums/a4fc4f0c-0812-4f61-94fd-a79c61419670.aspx Histidine MS Spectrum]

{{Amino acids}} {{Amino acid metabolism intermediates}} {{Histaminergics}}

{{commons category}}

{{Authority control}}

Category:Proteinogenic amino acids Category:Alpha-Amino acids Category:Basic amino acids Category:Essential amino acids Category:Imidazoles Category:Carbonic anhydrase activators <!--https://www.ncbi.nlm.nih.gov/pubmed/29478330--> Category:Aromatic amino acids