L-DOPA

L-DOPA
Ball-and-stick model of the zwitterionic form of L-DOPA found in the crystal structure
Names
IUPAC name
(S)-2-Amino-3-(3,4-dihydroxyphenyl)propanoic acid
Other names
l-3,4-Dihydroxyphenylalanine; Levodopa
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
DrugBank
ECHA InfoCard 100.000.405 Edit this at Wikidata
EC Number
  • 200-445-2
KEGG
UNII
  • InChI=1S/C9H11NO4/c10-6(9(13)14)3-5-1-2-7(11)8(12)4-5/h1-2,4,6,11-12H,3,10H2,(H,13,14)/t6-/m0/s1
    Key: WTDRDQBEARUVNC-LURJTMIESA-N
  • C1=CC(=C(C=C1C[C@@H](C(=O)O)N)O)O
Properties
C9H11NO4
Molar mass 197.19 g/mol
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

l-DOPA, also known as l-3,4-dihydroxyphenylalanine and used medically as levodopa, is made and used as part of the normal biology of some plants and animals, including humans. Humans, as well as a portion of the other animals that utilize l-DOPA, make it via biosynthesis from the amino acid l-tyrosine.

l-DOPA is the precursor to the neurotransmitters dopamine, norepinephrine (noradrenaline), and epinephrine (adrenaline), which are collectively known as catecholamines. Furthermore, l-DOPA itself mediates neurotrophic factor release by the brain and central nervous system. In some plant families (of the order Caryophyllales), l-DOPA is the central precursor of a biosynthetic pathway that produces a class of pigments called betalains.

l-DOPA can be manufactured and in its pure form is sold as a drug with the INNTooltip International Nonproprietary Name levodopa. As a drug, it is used in the treatment of Parkinson's disease and dopamine-responsive dystonia, as well as restless leg syndrome.

l-DOPA has a counterpart with opposite chirality, d-DOPA. As is true for many molecules, the human body produces only one of these isomers (the l-DOPA form). The enantiomeric purity of l-DOPA may be analyzed by determination of the optical rotation or by chiral thin-layer chromatography.

Biological role

Biosynthetic pathways for catecholamines and trace amines in the human brain
Graphic of catecholamine and trace amine biosynthesis
The image above contains clickable links
In humans, catecholamines and phenethylaminergic trace amines are derived from the amino acid L-phenylalanine.

l-DOPA is produced from the amino acid l-tyrosine by the enzyme tyrosine hydroxylase. l-DOPA can act as an l-tyrosine mimetic and be incorporated into proteins by mammalian cells in place of l-tyrosine, generating protease-resistant and aggregate-prone proteins in vitro and may contribute to neurotoxicity with chronic l-DOPA administration. It is also the precursor for the monoamine or catecholamine neurotransmitters dopamine, norepinephrine (noradrenaline), and epinephrine (adrenaline). Dopamine is formed by the decarboxylation of l-DOPA by aromatic l-amino acid decarboxylase (AADC).

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 l-DOPA administration in patients with Parkinson's disease or in the rare cases of patients with AADC enzyme deficiency.

l-Phenylalanine, l-tyrosine, and l-DOPA are all precursors to the biological pigment melanin. The enzyme tyrosinase catalyzes the oxidation of l-DOPA to the reactive intermediate dopaquinone, which reacts further, eventually leading to melanin oligomers. In addition, tyrosinase can convert tyrosine directly to l-DOPA in the presence of a reducing agent such as ascorbic acid.

Chemistry

L-DOPA, also known as L-3,4-dihydroxyphenylalanine or L-3-hydroxytyrosine, is an aromatic amino acid derived from L-phenylalanine and L-tyrosine. It is a phenethylamine, monoamine, and catecholamine, and is a biological precursor of the neurotransmitters dopamine (3,4-dihydroxyphenethylamine), norepinephrine (3,4,β-trihydroxyphenethylamine), and epinephrine (3,4,β-trihydroxy-N-methylphenethylamine).

Synthesis

Synthesis of l-DOPA via hydrogenation with C2-symmetric diphosphine.

History

l-DOPA was first isolated from the seeds of the Vicia faba (broad bean) plant in 1913 by Swiss biochemist Markus Guggenheim.

The 2001 Nobel Prize in Chemistry was also related to 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 l-DOPA.

Other organisms

Marine adhesion

l-DOPA is a key compound in the formation of marine adhesive proteins, such as those found in mussels. It is believed to be responsible for the water-resistance and rapid curing abilities of these proteins. l-DOPA may also be used to prevent surfaces from fouling by bonding antifouling polymers to a susceptible substrate. The versatile chemistry of l-DOPA can be exploited in nanotechnology. For example, DOPA-containing self-assembling peptides were found to form functional nanostructures, adhesives and gels.

In plants and in the environment

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. Its effect is strongly dependent on the pH and the reactivity of iron in the soil. A 2025 study reported that exogenous L-DOPA triggers a rapid iron-deficiency response in plants, independent of their iron nutritional status. L-DOPA was also suggested to protect Arabidopsis plants against cadmium toxicity.

L-DOPA can also be found in cephalopod ink.

Use as a medication and supplement

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.

References

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  15. ↑ Knowles WS (1983). "Asymmetric hydrogenation". Accounts of Chemical Research. 16 (3): 106–112. doi:10.1021/ar00087a006.
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  18. ↑ Waite JH, Andersen NH, Jewhurst S, Sun C (2005). "Mussel Adhesion: Finding the Tricks Worth Mimicking". J Adhesion. 81 (3–4): 1–21. doi:10.1080/00218460590944602. S2CID 136967853.
  19. ↑ "Study Reveals Details Of Mussels' Tenacious Bonds". Science Daily. 16 August 2006. Retrieved 30 September 2013.
  20. ↑ "Mussel Adhesive Protein Mimetics". Archived from the original on 29 May 2006.
  21. ↑ Giuri D, Ravarino P, Tomasini C (June 2021). "L-Dopa in small peptides: an amazing functionality to form supramolecular materials". Organic & Biomolecular Chemistry. 19 (21): 4622–4636. doi:10.1039/D1OB00378J. hdl:11585/840774. PMID 33978030. S2CID 234474122.
  22. ↑ Fichman G, Adler-Abramovich L, Manohar S, Mironi-Harpaz I, Guterman T, Seliktar D, et al. (July 2014). "Seamless metallic coating and surface adhesion of self-assembled bioinspired nanostructures based on di-(3,4-dihydroxy-L-phenylalanine) peptide motif". ACS Nano. 8 (7): 7220–7228. Bibcode:2014ACSNa...8.7220F. doi:10.1021/nn502240r. PMC 4108209. PMID 24936704.
  23. ↑ Fichman G, Guterman T, Adler-Abramovich L, Gazit E (August 2014). "The Use of the Calcitonin Minimal Recognition Module for the Design of DOPA-Containing Fibrillar Assemblies". Nanomaterials. 4 (3): 726–740. doi:10.3390/nano4030726. PMC 5304689. PMID 28344244.
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  25. ↑ Maity S, Nir S, Zada T, Reches M (October 2014). "Self-assembly of a tripeptide into a functional coating that resists fouling". Chemical Communications. 50 (76): 11154–11157. doi:10.1039/C4CC03578J. PMID 25110984.
  26. ↑ Fujii Y, Shibuya T, Yasuda T (1991). "L-3,4-Dihydroxyphenylalanine as an Allelochemical Candidate from Mucuna pruriens (L.) DC. var. utilis". Agricultural and Biological Chemistry. 55 (2): 617–618. doi:10.1080/00021369.1991.10870627.
  27. ↑ Hsieh EJ, Liao SW, Chang CY, Tseng CH, Wang SL, Grillet L (2023). "L-DOPA induces iron accumulation in roots of Ipomoea aquatica and Arabidopsis thaliana in a pH-dependent manner". Botanical Studies. 64 (24) 24: 617–618. Bibcode:2023BotSt..64...24H. doi:10.1186/s40529-023-00396-7. PMC 10449704. PMID 37620733.
  28. ↑ Hsieh EJ, Rusli MH, Liao SW, Tseng CH, Chang CY, Wang SL, et al. (2025). "L-DOPA elicits iron deficiency response through root-to-shoot signaling and independently of the canonical regulatory pathway". New Phytologist nph.70823. doi:10.1111/nph.70823. PMID 41408918.
  29. ↑ Chang CY, Hsieh EJ, Wang SL, Grillet L (2025). "L-DOPA promotes cadmium tolerance and modulates iron deficiency genes in Arabidopsis thaliana". Physiologia Plantarum. 177 (1) e70024. Bibcode:2025PPlan.177E0024C. doi:10.1111/ppl.70024. PMID 39727040.
  30. ↑ Lucero MT, Farrington H, Gilly WF (August 1994). "Quantification of L-Dopa and Dopamine in Squid Ink: Implications for Chemoreception". The Biological Bulletin. 187 (1): 55–63. Bibcode:1994BiolB.187...55L. doi:10.2307/1542165. ISSN 1939-8697. JSTOR 1542165. PMID 29281314.