| Revision as of 13:01, 15 February 2012 editBeetstra (talk | contribs)Edit filter managers, Administrators172,031 edits Saving copy of the {{drugbox}} taken from revid 474700256 of page Aminolevulinic_acid for the Chem/Drugbox validation project (updated: 'DrugBank'). |
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{{Short description|Endogenous non-proteinogenic amino acid}} |
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{{ambox | text = This page contains a copy of the infobox ({{tl|drugbox}}) taken from revid of page ] with values updated to verified values.}} |
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{{Use dmy dates|date=March 2024}} |
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{{drugbox |
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{{cs1 config|name-list-style=vanc|display-authors=6}} |
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{{Infobox drug |
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| verifiedrevid = 456688550 |
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| Watchedfields = changed |
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| IUPAC_name = 5-amino-4-oxo-pentanoic acid |
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| verifiedrevid = 476997949 |
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| drug_name = δ-Aminolevulinic acid |
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| image = Aminolevulinic acid.svg |
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| image = Aminolevulinic acid.svg |
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| alt = |
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| imagename = δ-Aminolevulinic acid |
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<!--Clinical data--> |
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<!-- Clinical data --> |
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| pregnancy_category = |
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| pronounce = |
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| tradename = Levulan, NatuALA, Ameluz, others |
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| legal_status = |
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| Drugs.com = {{drugs.com|monograph|aminolevulinic-acid}} |
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| routes_of_administration = |
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| MedlinePlus = a607062 |
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| DailyMedID = Aminolevulinic acid |
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| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X --> |
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| pregnancy_AU_comment = |
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| pregnancy_category= |
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| routes_of_administration = ], ] |
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| ATC_prefix = L01 |
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| ATC_suffix = XD04 |
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| ATC_supplemental = |
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| legal_CA = Rx-only |
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| legal_CA_comment = <ref>{{cite web | title=Levulan Kerastick Product information | website=Health Canada | date=25 April 2012 | url=https://health-products.canada.ca/dpd-bdpp/info.do?lang=en&code=67875 | access-date=4 June 2022}}</ref><ref>{{cite web | title=Gleolan Product information | website=Health Canada | date=25 April 2012 | url=https://health-products.canada.ca/dpd-bdpp/info.do?lang=en&code=99429 | access-date=4 June 2022}}</ref> |
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| legal_US = Rx-only |
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| legal_EU = Rx-only |
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| legal_status = Rx-only |
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<!--Pharmacokinetic data--> |
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<!-- Pharmacokinetic data --> |
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| bioavailability = |
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| bioavailability = |
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| protein_bound = |
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| protein_bound = |
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| elimination_half-life = |
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| elimination_half-life = |
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<!--Identifiers--> |
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<!-- Identifiers --> |
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| IUPHAR_ligand = 4784 |
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| CASNo_Ref = {{cascite|correct|CAS}} |
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| CAS_number_Ref = {{cascite|correct|??}} |
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| CAS_number_Ref = {{cascite|correct|??}} |
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| CAS_number = 106-60-5 |
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| CAS_number = 106-60-5 |
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| ATC_prefix = L01 |
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| ATC_suffix = XD04 |
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| ATC_supplemental = |
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| PubChem = 137 |
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| PubChem = 137 |
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| DrugBank_Ref = {{drugbankcite|changed|drugbank}} |
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| DrugBank_Ref = {{drugbankcite|correct|drugbank}} |
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| DrugBank = DB00855 |
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| DrugBank = DB00855 |
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| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} |
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| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} |
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| ChEMBL_Ref = {{ebicite|correct|EBI}} |
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| ChEMBL_Ref = {{ebicite|correct|EBI}} |
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| ChEMBL = 601 |
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| ChEMBL = 601 |
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| synonyms = 5-aminolevulinic acid |
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<!--Chemical data--> |
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<!-- Chemical data --> |
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| IUPAC_name = 5-Amino-4-oxo-pentanoic acid |
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| C=5 | H=9 | N=1 | O=3 |
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| C=5 | H=9 | N=1 | O=3 |
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| molecular_weight = 131.13 g/mol |
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| smiles = O=C(CN)CCC(=O)O |
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| smiles = O=C(CN)CCC(=O)O |
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| InChI = 1/C5H9NO3/c6-3-4(7)1-2-5(8)9/h1-3,6H2,(H,8,9) |
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| InChIKey = ZGXJTSGNIOSYLO-UHFFFAOYAL |
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| StdInChI_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChI_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChI = 1S/C5H9NO3/c6-3-4(7)1-2-5(8)9/h1-3,6H2,(H,8,9) |
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| StdInChI = 1S/C5H9NO3/c6-3-4(7)1-2-5(8)9/h1-3,6H2,(H,8,9) |
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| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChIKey = ZGXJTSGNIOSYLO-UHFFFAOYSA-N |
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| StdInChIKey = ZGXJTSGNIOSYLO-UHFFFAOYSA-N |
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| melting_point= 118 |
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}} |
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}} |
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'''δ-Aminolevulinic acid''' (also '''dALA''', '''δ-ALA''', '''5ALA''' or '''5-aminolevulinic acid'''), an endogenous ], is the first compound in the ] synthesis pathway, the pathway that leads to ]<ref name=Gardener1988>{{cite journal | vauthors = Gardener LC, Cox TM | year = 1988 | title = Biosynthesis of heme in immature erythroid cells | journal = The Journal of Biological Chemistry | volume = 263 | pages = 6676–6682 | doi = 10.1016/S0021-9258(18)68695-8 | doi-access = free }}</ref> in mammals, as well as ]<ref name=Wettstein1995>{{cite journal | vauthors = Von Wettstein D, Gough S, Kannangara CG | title = Chlorophyll Biosynthesis | journal = The Plant Cell | volume = 7 | issue = 7 | pages = 1039–1057 | date = July 1995 | pmid = 12242396 | pmc = 160907 | doi = 10.1105/tpc.7.7.1039 }}</ref> in plants. |
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5ALA is used in photodynamic detection and surgery of cancer.<ref name="Wagnières2014">Wagnières, G.., Jichlinski, P., Lange, N., Kucera, P., Van den Bergh, H. (2014). Detection of Bladder Cancer by Fluorescence Cystoscopy: From Bench to Bedside - the Hexvix Story. Handbook of Photomedicine, 411-426.</ref><ref name="Eyüpoglu2013">{{cite journal | vauthors = Eyüpoglu IY, Buchfelder M, Savaskan NE | title = Surgical resection of malignant gliomas-role in optimizing patient outcome | journal = Nature Reviews. Neurology | volume = 9 | issue = 3 | pages = 141–151 | date = March 2013 | pmid = 23358480 | doi = 10.1038/nrneurol.2012.279 | s2cid = 20352840 }}</ref><ref name=StummerW2006>{{cite journal | vauthors = Stummer W, Pichlmeier U, Meinel T, Wiestler OD, Zanella F, Reulen HJ | title = Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: a randomised controlled multicentre phase III trial | journal = The Lancet. Oncology | volume = 7 | issue = 5 | pages = 392–401 | date = May 2006 | pmid = 16648043 | doi = 10.1016/s1470-2045(06)70665-9 }}</ref><ref name="Eyüpoglu2012">{{cite journal | vauthors = Eyüpoglu IY, Hore N, Savaskan NE, Grummich P, Roessler K, Buchfelder M, Ganslandt O | title = Improving the extent of malignant glioma resection by dual intraoperative visualization approach | journal = PLOS ONE | volume = 7 | issue = 9 | pages = e44885 | year = 2012 | pmid = 23049761 | pmc = 3458892 | doi = 10.1371/journal.pone.0044885 | bibcode = 2012PLoSO...744885E | doi-access = free }}</ref> |
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==Medical uses== |
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As a precursor of a photosensitizer, 5ALA is also used as an add-on agent for ].<ref>{{cite journal | vauthors = Yew YW, Lai YC, Lim YL, Chong WS, Theng C | title = Photodynamic Therapy With Topical 5% 5-Aminolevulinic Acid for the Treatment of Truncal Acne in Asian Patients | journal = Journal of Drugs in Dermatology | volume = 15 | issue = 6 | pages = 727–732 | date = June 2016 | pmid = 27272080 }}</ref> In contrast to larger photosensitizer molecules, it is predicted by computer simulations to be able to penetrate tumor cell membranes.<ref>{{cite journal | vauthors = Erdtman E |title=Modelling the behavior of 5-aminolevulinic acid and its alkyl esters in a lipid bilayer |journal=Chemical Physics Letters |volume=463 |issue=1–3 |page=178 |doi=10.1016/j.cplett.2008.08.021|year=2008 |bibcode=2008CPL...463..178E }}</ref> |
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===Cancer diagnosis=== |
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Photodynamic detection is the use of photosensitive drugs with a light source of the right wavelength for the detection of cancer, using fluorescence of the drug.<ref name="Wagnières2014"/> 5ALA, or derivatives thereof, can be used to visualize bladder cancer by fluorescence imaging.<ref name="Wagnières2014"/> |
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===Cancer treatment=== |
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Aminolevulinic acid is being studied for ] (PDT) in a number of types of cancer.<ref>{{cite journal | vauthors = Inoue K | title = 5-Aminolevulinic acid-mediated photodynamic therapy for bladder cancer | journal = International Journal of Urology | volume = 24 | issue = 2 | pages = 97–101 | date = February 2017 | pmid = 28191719 | doi = 10.1111/iju.13291 | doi-access = free }}</ref> It is not currently a first line treatment for ].<ref name=Qum2013>{{cite journal | vauthors = Qumseya BJ, David W, Wolfsen HC | title = Photodynamic Therapy for Barrett's Esophagus and Esophageal Carcinoma | journal = Clinical Endoscopy | volume = 46 | issue = 1 | pages = 30–37 | date = January 2013 | pmid = 23423151 | pmc = 3572348 | doi = 10.5946/ce.2013.46.1.30 }}</ref> Its use in ] is currently experimental.<ref name=Tet2014>{{cite journal | vauthors = Tetard MC, Vermandel M, Mordon S, Lejeune JP, Reyns N | title = Experimental use of photodynamic therapy in high grade gliomas: a review focused on 5-aminolevulinic acid | journal = Photodiagnosis and Photodynamic Therapy | volume = 11 | issue = 3 | pages = 319–330 | date = September 2014 | pmid = 24905843 | doi = 10.1016/j.pdpdt.2014.04.004 | s2cid = 38534019 | url = https://hal.archives-ouvertes.fr/hal-01181357/file/Tetard-Vermandel-Mordon-Lejeune-Reyns.pdf }}</ref> It has been studied in a number of gynecological cancers.<ref>{{cite journal | vauthors = Shishkova N, Kuznetsova O, Berezov T | title = Photodynamic therapy for gynecological diseases and breast cancer | journal = Cancer Biology & Medicine | volume = 9 | issue = 1 | pages = 9–17 | date = March 2012 | pmid = 23691448 | pmc = 3643637 | doi = 10.3969/j.issn.2095-3941.2012.01.002 }}</ref> |
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Aminolevulinic acid is indicated in adults for visualization of malignant tissue during surgery for malignant glioma (World Health Organization grade III and IV).<ref>{{cite web | title=Gliolan EPAR | website=] (EMA) | date=17 September 2018 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/gliolan | access-date=6 January 2021}}</ref> It is used to visualise tumorous tissue in ] procedures.<ref name="Eyüpoglu2013"/> Studies since 2006 have shown that the intraoperative use of this guiding method may reduce the tumour residual volume and prolong ] in people with ]s.<ref name=StummerW2006 /><ref name="Eyüpoglu2012"/> The ] approved aminolevulinic acid hydrochloride (ALA HCL) for this use in 2017.<ref>FDA Approves Fluorescing Agent for Glioma Surgery.June 2017</ref> |
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=== Intra-operative Cancer Delineation === |
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Aminolevulinic acid utilization is promising in the field of cancer delineation, particularly in the context of ]. This compound is utilized to enhance the visualization of ] tissues during surgical procedures. When administered to patients, 5-ALA is metabolized to ] preferentially in cancer cells, leading to their ] under specific ].<ref>{{cite journal | vauthors = Hadjipanayis CG, Widhalm G, Stummer W | title = What is the Surgical Benefit of Utilizing 5-Aminolevulinic Acid for Fluorescence-Guided Surgery of Malignant Gliomas? | journal = Neurosurgery | volume = 77 | issue = 5 | pages = 663–673 | date = November 2015 | pmid = 26308630 | pmc = 4615466 | doi = 10.1227/NEU.0000000000000929 }}</ref> This fluorescence aids surgeons in real-time identification and precise removal of cancerous tissue, reducing the likelihood of leaving residual tumor cells behind. This innovative approach has shown success in various cancer types, including ] and spine ], ], and ].<ref>{{cite journal | vauthors = Maragkos GA, Schüpper AJ, Lakomkin N, Sideras P, Price G, Baron R, Hamilton T, Haider S, Lee IY, Hadjipanayis CG, Robin AM | title = Fluorescence-Guided High-Grade Glioma Surgery More Than Four Hours After 5-Aminolevulinic Acid Administration | journal = Frontiers in Neurology | volume = 12 | pages = 644804 | date = 2021 | pmid = 33767664 | pmc = 7985355 | doi = 10.3389/fneur.2021.644804 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Albalkhi I, Shafqat A, Bin-Alamer O, Abou Al-Shaar AR, Mallela AN, Fernández-de Thomas RJ, Zinn PO, Gerszten PC, Hadjipanayis CG, Abou-Al-Shaar H | title = Fluorescence-guided resection of intradural spinal tumors: a systematic review and meta-analysis | journal = Neurosurgical Review | volume = 47 | issue = 1 | pages = 10 | date = December 2023 | pmid = 38085385 | doi = 10.1007/s10143-023-02230-x | s2cid = 266164983 }}</ref><ref>{{cite journal | vauthors = Filip P, Lerner DK, Kominsky E, Schupper A, Liu K, Khan NM, Roof S, Hadjipanayis C, Genden E, Iloreta AM | title = 5-Aminolevulinic Acid Fluorescence-Guided Surgery in Head and Neck Squamous Cell Carcinoma | journal = The Laryngoscope | volume = 134 | issue = 2 | pages = 741–748 | date = February 2024 | pmid = 37540051 | doi = 10.1002/lary.30910 | s2cid = 260485667 }}</ref> |
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==Side effects== |
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Side effects may include ] and ].<ref name=Qum2013/> ] may also occur.<ref name=Tet2014/> Deaths have also resulted.<ref name=Qum2013/> |
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==Biosynthesis== |
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In non-photosynthetic eukaryotes such as animals, fungi, and protozoa, as well as the class ] of bacteria, it is produced by the enzyme ], from ] and ]. This reaction is known as the Shemin pathway, which occurs in mitochondria.<ref>Ajioka, James; Soldati, Dominique, eds. (13 September 2007). "22". Toxoplasma: Molecular and Cellular Biology (1 ed.). Taylor & Francis. p. 415. {{ISBN|9781904933342}}</ref> |
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In plants, algae, bacteria (except for the class Alphaproteobacteria) and archaea, it is produced from glutamic acid via glutamyl-tRNA and glutamate-1-semialdehyde. The enzymes involved in this pathway are glutamyl-tRNA synthetase, ], and ]. This pathway is known as the C5 or Beale pathway.<ref>{{cite journal | vauthors = Beale SI | title = Biosynthesis of the Tetrapyrrole Pigment Precursor, delta-Aminolevulinic Acid, from Glutamate | journal = Plant Physiology | volume = 93 | issue = 4 | pages = 1273–1279 | date = August 1990 | pmid = 16667613 | pmc = 1062668 | doi = 10.1104/pp.93.4.1273 }}</ref><ref>Willows, R.D. (2004). "Chlorophylls". In Goodman, Robert M. Encyclopaedia of Plant and Crop Science. Marcel Dekker. pp. 258–262. {{ISBN|0-8247-4268-0}}</ref> In most plastid-containing species, glutamyl-tRNA is encoded by a plastid gene, and the transcription, as well as the following steps of C5 pathway, take place in plastids.<ref>Biswal, Basanti; Krupinska, Karin; Biswal, Udaya, eds. (2013). Plastid Development in Leaves during Growth and Senescence (Advances in Photosynthesis and Respiration). Dordrecht: Springer. p. 508. {{ISBN|9789400757233}}</ref> |
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==Importance in humans== |
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===Activation of mitochondria=== |
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In humans, 5ALA is a precursor to ].<ref name=Gardener1988 /> Biosynthesized, 5ALA goes through a series of transformations in the ] and finally gets converted to ] IX inside the ].<ref name=Malik1979>{{cite journal | vauthors = Malik Z, Djaldetti M | title = 5-Aminolevulinic acid stimulation of porphyrin and hemoglobin synthesis by uninduced Friend erythroleukemic cells | journal = Cell Differentiation | volume = 8 | issue = 3 | pages = 223–233 | date = June 1979 | pmid = 288514 | doi = 10.1016/0045-6039(79)90049-6 }}</ref><ref name=Olivo2011>{{cite journal | vauthors = Olivo M, Bhuvaneswari R, Keogh I | title = Advances in bio-optical imaging for the diagnosis of early oral cancer | journal = Pharmaceutics | volume = 3 | issue = 3 | pages = 354–378 | date = July 2011 | pmid = 24310585 | pmc = 3857071 | doi = 10.3390/pharmaceutics3030354 | doi-access = free }}</ref> This protoporphyrin molecule chelates with iron in presence of enzyme ] to produce ].<ref name=Malik1979 /><ref name=Olivo2011 /> |
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Heme increases the mitochondrial activity thereby helping in activation of respiratory system ] and ]<ref name=Ogura2011>{{cite journal | vauthors = Ogura S, Maruyama K, Hagiya Y, Sugiyama Y, Tsuchiya K, Takahashi K, Abe F, Tabata K, Okura I, Nakajima M, Tanaka T | title = The effect of 5-aminolevulinic acid on cytochrome c oxidase activity in mouse liver | journal = BMC Research Notes | volume = 4 | issue = 4 | pages = 66 | date = March 2011 | pmid = 21414200 | pmc = 3068109 | doi = 10.1186/1756-0500-4-66 | doi-access = free }}</ref> leading to formation of ] (ATP) for adequate supply of energy to the body.<ref name=Ogura2011 /> |
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===Accumulation of Protoporphyrin IX=== |
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Cancer cells lack or have reduced ferrochelatase activity and this results in accumulation of ] IX, a fluorescent substance that can easily be visualized.<ref name="Wagnières2014"/> |
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===Induction of Heme Oxygenase-1 (HO-1)=== |
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Excess heme is converted in macrophages to ] and ferrous ions by the enzyme HO-1. ] formed further gets converted to ] and ].<ref name=Loboda2016>{{cite journal | vauthors = Loboda A, Damulewicz M, Pyza E, Jozkowicz A, Dulak J | title = Role of Nrf2/HO-1 system in development, oxidative stress response and diseases: an evolutionarily conserved mechanism | journal = Cellular and Molecular Life Sciences | volume = 73 | issue = 17 | pages = 3221–3247 | date = September 2016 | pmid = 27100828 | pmc = 4967105 | doi = 10.1007/s00018-016-2223-0 }}</ref> Biliverdin and Bilirubin are potent anti oxidants and regulate important biological processes like ], ], ], ] and ].<ref name=Loboda2016 /> |
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==Plants== |
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In plants, production of 5-ALA is the step on which the speed of synthesis of ] is regulated.<ref name=Wettstein1995 /> Plants that are fed by external 5-ALA accumulate toxic amounts of chlorophyll precursor, ], indicating that the synthesis of this intermediate is not suppressed anywhere downwards in the chain of reaction. ] is a strong photosensitizer in plants.<ref>{{cite journal | vauthors = Kotzabasis K, Senger H | year = 1990 | title = The influence of 5-aminolevulinic acid on protochlorophyllide and protochlorophyll accumulation in dark-grown Scenedesmus | journal = Z. Naturforsch. | volume = 45 | issue = 1–2 | pages = 71–73 | doi = 10.1515/znc-1990-1-212 | s2cid = 42965243 | doi-access = free }}</ref> Controlled spraying of 5-ALA at lower doses (up to 150 mg/L) can however help protect plants from stress and encourage growth.<ref>{{cite journal | vauthors = Kosar F, Akram NA, Ashraf M |title=Exogenously-applied 5-aminolevulinic acid modulates some key physiological characteristics and antioxidative defense system in spring wheat (Triticum aestivum L.) seedlings under water stress |journal=South African Journal of Botany |date=January 2015 |volume=96 |pages=71–77 |doi=10.1016/j.sajb.2014.10.015|doi-access=free }}</ref> |
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== References == |
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{{reflist}} |
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{{Chemotherapeutic agents}} |
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{{Heme metabolism intermediates}} |
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{{Non-proteinogenic amino acids}} |
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{{Portal bar | Medicine}} |
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{{DEFAULTSORT:Aminolevulinic Acid}} |
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