L-DOPA#Marine adhesion

{{Phenylalanine biosynthesis|align=right}}

{{sm|l}}-DOPA is produced from the amino acid {{sm|l}}-tyrosine by the enzyme tyrosine hydroxylase. {{sm|l}}-DOPA can act as an {{sm|l}}-tyrosine mimetic and be incorporated into proteins by mammalian cells in place of {{sm|l}}-tyrosine, generating protease-resistant and aggregate-prone proteins in vitro and may contribute to neurotoxicity with chronic {{sm|l}}-DOPA administration.{{cite journal | vauthors = Rodgers KJ | title = Non-protein amino acids and neurodegeneration: the enemy within | journal = Experimental Neurology | volume = 253 | pages = 192–196 | date = March 2014 | pmid = 24374297 | doi = 10.1016/j.expneurol.2013.12.010 | s2cid = 2288729 }}

It is also the precursor for the monoamine or catecholamine neurotransmitters dopamine, norepinephrine (noradrenaline), and epinephrine (adrenaline). Dopamine is formed by the decarboxylation of {{sm|l}}-DOPA by aromatic L-amino acid decarboxylase (AADC).

{{sm|l}}-DOPA can be directly metabolized by catechol-O-methyl transferase to 3-O-methyldopa, and then further to vanillactic acid. This metabolic pathway is nonexistent in the healthy body, but becomes important after peripheral {{sm|l}}-DOPA administration in patients with Parkinson's disease or in the rare cases of patients with AADC enzyme deficiency.{{cite journal | vauthors = Hyland K, Clayton PT | title = Aromatic L-amino acid decarboxylase deficiency: diagnostic methodology | journal = Clinical Chemistry | volume = 38 | issue = 12 | pages = 2405–10 | date = December 1992 | pmid = 1281049 | doi = 10.1093/clinchem/38.12.2405| url = http://www.clinchem.org/cgi/reprint/38/12/2405.pdf | access-date = 16 October 2008 | archive-url = https://web.archive.org/web/20110607122144/http://www.clinchem.org/cgi/reprint/38/12/2405.pdf | archive-date = 7 June 2011 | url-status = dead | doi-access = free }}

{{sm|l}}-Phenylalanine, {{sm|l}}-tyrosine, and {{sm|l}}-DOPA are all precursors to the biological pigment melanin. The enzyme tyrosinase catalyzes the oxidation of {{sm|l}}-DOPA to the reactive intermediate dopaquinone, which reacts further, eventually leading to melanin oligomers. In addition, tyrosinase can convert tyrosine directly to {{sm|l}}-DOPA in the presence of a reducing agent such as ascorbic acid.{{cite journal | vauthors = Ito S, Kato T, Shinpo K, Fujita K | title = Oxidation of tyrosine residues in proteins by tyrosinase. Formation of protein-bonded 3,4-dihydroxyphenylalanine and 5-S-cysteinyl-3,4-dihydroxyphenylalanine | journal = The Biochemical Journal | volume = 222 | issue = 2 | pages = 407–11 | date = September 1984 | pmid = 6433900 | pmc = 1144193 | doi = 10.1042/bj2220407 }}

{{sm|l}}-DOPA was first isolated from the seeds of the Vicia faba (broad bean) plant in 1913 by Swiss biochemist Markus Guggenheim.{{cite journal | vauthors = Ovallath S, Sulthana B | title = Levodopa: History and Therapeutic Applications | journal = Annals of Indian Academy of Neurology | volume = 20 | issue = 3 | pages = 185–189 | date = 2017 | pmid = 28904446 | pmc = 5586109 | doi = 10.4103/aian.AIAN_241_17 | doi-access = free }}

The 2001 Nobel Prize in Chemistry was also related to {{sm|l}}-DOPA: the Nobel Committee awarded one-quarter of the prize to William S. Knowles for his work on chirally catalysed hydrogenation reactions, the most noted example of which was used for the synthesis of {{sm|l}}-DOPA.{{cite journal | doi = 10.1021/ar00087a006 | title = Asymmetric hydrogenation | year = 1983 | vauthors = Knowles WS | journal = Accounts of Chemical Research | volume = 16 | issue = 3 | pages = 106–112}}{{cite web | url = http://www.chem.wisc.edu/areas/reich/syntheses/dopa-monsanto-knowles.htm | title = Synthetic scheme for total synthesis of DOPA, L- (Monsanto) | publisher = UW Madison, Department of Chemistry | access-date = 30 September 2013}}{{cite journal| vauthors = Knowles WS |title=Application of organometallic catalysis to the commercial production of L-DOPA|journal=Journal of Chemical Education|date=March 1986|volume=63|issue=3|pages=222|doi=10.1021/ed063p222|bibcode=1986JChEd..63..222K}}

: File:L-dopaSyn.svg

{{sm|l}}-DOPA is a key compound in the formation of marine adhesive proteins, such as those found in mussels.{{cite journal | vauthors = Waite JH, Andersen NH, Jewhurst S, Sun C | title=Mussel Adhesion: Finding the Tricks Worth Mimicking | journal=J Adhesion | volume=81 | year=2005 | pages=1–21 | doi=10.1080/00218460590944602 | issue=3–4 | s2cid=136967853 }}{{cite web | url = https://www.sciencedaily.com/releases/2006/08/060816024159.htm | title = Study Reveals Details Of Mussels' Tenacious Bonds | publisher = Science Daily | date = 16 August 2006 | access-date = 30 September 2013}} It is believed to be responsible for the water-resistance and rapid curing abilities of these proteins. {{sm|l}}-DOPA may also be used to prevent surfaces from fouling by bonding antifouling polymers to a susceptible substrate.{{cite web | url = http://biomaterials.bme.northwestern.edu/mussel.asp | title = Mussel Adhesive Protein Mimetics | archive-url = https://web.archive.org/web/20060529181142/http://biomaterials.bme.northwestern.edu/mussel.asp | archive-date=29 May 2006 }} The versatile chemistry of {{sm|l}}-DOPA can be exploited in nanotechnology.{{cite journal | vauthors = Giuri D, Ravarino P, Tomasini C | title = L-Dopa in small peptides: an amazing functionality to form supramolecular materials | journal = Organic & Biomolecular Chemistry | volume = 19 | issue = 21 | pages = 4622–4636 | date = June 2021 | pmid = 33978030 | doi = 10.1039/D1OB00378J | s2cid = 234474122 | hdl = 11585/840774 | hdl-access = free }} For example, DOPA-containing self-assembling peptides were found to form functional nanostructures, adhesives and gels.{{cite journal | vauthors = Fichman G, Adler-Abramovich L, Manohar S, Mironi-Harpaz I, Guterman T, Seliktar D, Messersmith PB, Gazit E | title = Seamless metallic coating and surface adhesion of self-assembled bioinspired nanostructures based on di-(3,4-dihydroxy-L-phenylalanine) peptide motif | journal = ACS Nano | volume = 8 | issue = 7 | pages = 7220–7228 | date = July 2014 | pmid = 24936704 | pmc = 4108209 | doi = 10.1021/nn502240r }}{{cite journal | vauthors = Fichman G, Guterman T, Adler-Abramovich L, Gazit E | title = The Use of the Calcitonin Minimal Recognition Module for the Design of DOPA-Containing Fibrillar Assemblies | journal = Nanomaterials | volume = 4 | issue = 3 | pages = 726–740 | date = August 2014 | pmid = 28344244 | pmc = 5304689 | doi = 10.3390/nano4030726 | doi-access = free }}{{cite journal | vauthors = Fichman G, Andrews C, Patel NL, Schneider JP | title = Antibacterial Gel Coatings Inspired by the Cryptic Function of a Mussel Byssal Peptide | journal = Advanced Materials | volume = 33 | issue = 40 | pages = e2103677 | date = October 2021 | pmid = 34423482 | pmc = 8492546 | doi = 10.1002/adma.202103677 | bibcode = 2021AdM....3303677F }}{{cite journal | vauthors = Maity S, Nir S, Zada T, Reches M | title = Self-assembly of a tripeptide into a functional coating that resists fouling | journal = Chemical Communications | volume = 50 | issue = 76 | pages = 11154–11157 | date = October 2014 | pmid = 25110984 | doi = 10.1039/C4CC03578J }}

In plants, L-DOPA functions as an allelochemical which inhibits the growth of certain species, and is produced and secreted by a few legume species such as the broad bean Vicia faba and the velvet bean Mucuna pruriens.{{cite journal | vauthors = Fujii Y, Shibuya T, Yasuda T| title = L-3,4-Dihydroxyphenylalanine as an Allelochemical Candidate from Mucuna pruriens (L.) DC. var. utilis | journal = Agricultural and Biological Chemistry | volume = 55 | issue = 2 | pages = 617–618 | date = 1991 | doi = 10.1080/00021369.1991.10870627 }} Its effect is strongly dependent on the pH and the reactivity of iron in the soil.{{cite journal | vauthors = Hsieh EJ, Liao SW, Chang CY, Tseng CH, Wang SL, Grillet L| title = L-DOPA induces iron accumulation in roots of Ipomoea aquatica and Arabidopsis thaliana in a pH-dependent manner | journal = Botanical Studies | volume = 64 | issue = 24 | pages = 617–618 | date = 2023 | pmid = 37620733 | pmc = 10449704 | doi = 10.1186/s40529-023-00396-7 | doi-access = free | bibcode = 2023BotSt..64...24H }} L-DOPA can also be found in cephalopod ink.{{Cite journal |last=Lucero |first=M. T. |last2=Farrington |first2=H. |last3=Gilly |first3=W. F. |date=August 1994 |title=Quantification of L-Dopa and Dopamine in Squid Ink: Implications for Chemoreception |url=https://pubmed.ncbi.nlm.nih.gov/29281314 |journal=The Biological Bulletin |volume=187 |issue=1 |pages=55–63 |doi=10.2307/1542165 |issn=1939-8697 |pmid=29281314}}

{{Main|Levodopa}}

L-DOPA is used medically under the name levodopa in the treatment of Parkinson's disease and certain other medical conditions. It is usually used in combination with a peripherally selective aromatic L-amino acid decarboxylase (AAAD) inhibitor such as carbidopa or benserazide. These agents increase the strength and duration of levodopa. Combination formulations include levodopa/carbidopa and levodopa/benserazide, as well as levodopa/carbidopa/entacapone.

L-DOPA is found in high amounts in Mucuna pruriens (velvet bean) and is available and used over-the-counter as a supplement.

{{Reflist}}

{{Supplements}}

{{Amino acids}}

{{Amino acid metabolism enzymes}}

{{Neurotransmitter metabolism intermediates}}

{{Dopamine receptor modulators}}

{{Phenethylamines}}

{{DEFAULTSORT:DOPA, L-}}

Category:Alpha-Amino acids

Category:Aromatic amino acids

Category:Carbonic anhydrase activators

Category:Catecholamines

Category:Dopamine agonists

Category:Monoamine precursors