L-DOPA explained

-DOPA, also known as -3,4-dihydroxyphenylalanine and used medically as levodopa, is made and used as part of the normal biology of some plants[1] and animals, including humans. Humans, as well as a portion of the other animals that utilize -DOPA, make it via biosynthesis from the amino acid -tyrosine.

-DOPA is the precursor to the neurotransmitters dopamine, norepinephrine (noradrenaline), and epinephrine (adrenaline), which are collectively known as catecholamines. Furthermore, -DOPA itself mediates neurotrophic factor release by the brain and CNS.[2] [3] In some plant families (of the order Caryophyllales), -DOPA is the central precursor of a biosynthetic pathway that produces a class of pigments called betalains.[4]

-DOPA can be manufactured and in its pure form is sold as a drug with the levodopa. Trade names include Sinemet, Pharmacopa, Atamet, and Stalevo. As a drug, it is used in the clinical treatment of Parkinson's disease and dopamine-responsive dystonia.

-DOPA has a counterpart with opposite chirality, -DOPA. As is true for many molecules, the human body produces only one of these isomers (the -DOPA form). The enantiomeric purity of -DOPA may be analyzed by determination of the optical rotation or by chiral thin-layer chromatography.[5]

Biological role

-DOPA is produced from the amino acid -tyrosine by the enzyme tyrosine hydroxylase. -DOPA can act as an -tyrosine mimetic and be incorporated into proteins by mammalian cells in place of -tyrosine, generating protease-resistant and aggregate-prone proteins in vitro and may contribute to neurotoxicity with chronic -DOPA administration.[6] It is also the precursor for the monoamine or catecholamine neurotransmitters dopamine, norepinephrine (noradrenaline), and epinephrine (adrenaline). Dopamine is formed by the decarboxylation of -DOPA by aromatic -amino acid decarboxylase (AADC).

-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 -DOPA administration in patients with Parkinson's disease or in the rare cases of patients with AADC enzyme deficiency.[7]

-Phenylalanine, -tyrosine, and -DOPA are all precursors to the biological pigment melanin. The enzyme tyrosinase catalyzes the oxidation of -DOPA to the reactive intermediate dopaquinone, which reacts further, eventually leading to melanin oligomers. In addition, tyrosinase can convert tyrosine directly to -DOPA in the presence of a reducing agent such as ascorbic acid.[8]

History

-dopa was first islolated from the seeds of the Vicia faba or broad bean plant in 1913 by Swiss biochemist Markus Guggenheim.[9]

The 2001 Nobel Prize in Chemistry was also related to -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 -DOPA.[10] [11] [12]

Other organisms

Marine adhesion

-DOPA is a key compound in the formation of marine adhesive proteins, such as those found in mussels.[13] [14] It is believed to be responsible for the water-resistance and rapid curing abilities of these proteins. -DOPA may also be used to prevent surfaces from fouling by bonding antifouling polymers to a susceptible substrate.[15] The versatile chemistry of -DOPA can be exploited in nanotechnology.[16] For example, DOPA-containing self-assembling peptides were found to form functional nanostructures, adhesives and gels.[17] [18] [19] [20]

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.[21] Its effect is strongly dependent on the pH and the reactivity of iron in the soil.[22]

Use as a medication and supplement

See main article: 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.

Notes and References

  1. Cohen PA, Avula B, Katragunta K, Khan I . Levodopa Content of Mucuna pruriens Supplements in the NIH Dietary Supplement Label Database . JAMA Neurology . 79 . 10 . 1085–1086 . October 2022 . 35939305 . 10.1001/jamaneurol.2022.2184 . 9361182 .
  2. Lopez VM, Decatur CL, Stamer WD, Lynch RM, McKay BS . L-DOPA is an endogenous ligand for OA1 . PLOS Biology . 6 . 9 . e236 . September 2008 . 18828673 . 2553842 . 10.1371/journal.pbio.0060236 . free .
  3. Hiroshima Y, Miyamoto H, Nakamura F, Masukawa D, Yamamoto T, Muraoka H, Kamiya M, Yamashita N, Suzuki T, Matsuzaki S, Endo I, Goshima Y . The protein Ocular albinism 1 is the orphan GPCR GPR143 and mediates depressor and bradycardic responses to DOPA in the nucleus tractus solitarii . British Journal of Pharmacology . 171 . 2 . 403–14 . January 2014 . 24117106 . 3904260 . 10.1111/bph.12459 .
  4. Polturak G, Breitel D, Grossman N, Sarrion-Perdigones A, Weithorn E, Pliner M, Orzaez D, Granell A, Rogachev I, Aharoni A . Elucidation of the first committed step in betalain biosynthesis enables the heterologous engineering of betalain pigments in plants . New Phytol . 210 . 1 . 269–283 . 2016 . 10.1111/nph.13796 . free . 26683006 .
  5. Martens J, Günther K, Schickedanz M . Resolution of Optical Isomers by Thin-Layer Chromatography: Enantiomeric Purity of Methyldopa . . 319 . 6 . 572–574 . 1986 . 10.1002/ardp.19863190618 . 97903386 .
  6. Rodgers KJ . Non-protein amino acids and neurodegeneration: the enemy within . Experimental Neurology . 253 . 192–196 . March 2014 . 24374297 . 10.1016/j.expneurol.2013.12.010 . 2288729 .
  7. Hyland K, Clayton PT . Aromatic L-amino acid decarboxylase deficiency: diagnostic methodology . Clinical Chemistry . 38 . 12 . 2405–10 . December 1992 . 1281049 . 10.1093/clinchem/38.12.2405. 16 October 2008 . https://web.archive.org/web/20110607122144/http://www.clinchem.org/cgi/reprint/38/12/2405.pdf . 7 June 2011 . dead . free .
  8. Ito S, Kato T, Shinpo K, Fujita K . Oxidation of tyrosine residues in proteins by tyrosinase. Formation of protein-bonded 3,4-dihydroxyphenylalanine and 5-S-cysteinyl-3,4-dihydroxyphenylalanine . The Biochemical Journal . 222 . 2 . 407–11 . September 1984 . 6433900 . 1144193 . 10.1042/bj2220407 .
  9. Ovallath S, Sulthana B . Levodopa: History and Therapeutic Applications . Annals of Indian Academy of Neurology . 20 . 3 . 185–189 . 2017 . 28904446 . 5586109 . 10.4103/aian.AIAN_241_17 . free .
  10. 10.1021/ar00087a006 . Asymmetric hydrogenation . 1983 . Knowles WS . Accounts of Chemical Research . 16 . 3 . 106–112.
  11. Web site: Synthetic scheme for total synthesis of DOPA, L- (Monsanto) . UW Madison, Department of Chemistry . 30 September 2013.
  12. Knowles WS . Application of organometallic catalysis to the commercial production of L-DOPA. Journal of Chemical Education. March 1986. 63. 3. 222. 10.1021/ed063p222. 1986JChEd..63..222K.
  13. Waite JH, Andersen NH, Jewhurst S, Sun C . Mussel Adhesion: Finding the Tricks Worth Mimicking . J Adhesion . 81 . 2005 . 1–21 . 10.1080/00218460590944602 . 3–4 . 136967853 .
  14. Web site: Study Reveals Details Of Mussels' Tenacious Bonds . Science Daily . 16 August 2006 . 30 September 2013.
  15. Web site: Mussel Adhesive Protein Mimetics . https://web.archive.org/web/20060529181142/http://biomaterials.bme.northwestern.edu/mussel.asp . 29 May 2006 .
  16. Giuri D, Ravarino P, Tomasini C . L-Dopa in small peptides: an amazing functionality to form supramolecular materials . Organic & Biomolecular Chemistry . 19 . 21 . 4622–4636 . June 2021 . 33978030 . 10.1039/D1OB00378J . 234474122 . 11585/840774 . free .
  17. Fichman G, Adler-Abramovich L, Manohar S, Mironi-Harpaz I, Guterman T, Seliktar D, Messersmith PB, Gazit E . 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 . July 2014 . 24936704 . 4108209 . 10.1021/nn502240r .
  18. Fichman G, Guterman T, Adler-Abramovich L, Gazit E . The Use of the Calcitonin Minimal Recognition Module for the Design of DOPA-Containing Fibrillar Assemblies . Nanomaterials . 4 . 3 . 726–740 . August 2014 . 28344244 . 5304689 . 10.3390/nano4030726 . free .
  19. Fichman G, Andrews C, Patel NL, Schneider JP . Antibacterial Gel Coatings Inspired by the Cryptic Function of a Mussel Byssal Peptide . Advanced Materials . 33 . 40 . e2103677 . October 2021 . 34423482 . 8492546 . 10.1002/adma.202103677 . 2021AdM....3303677F .
  20. Maity S, Nir S, Zada T, Reches M . Self-assembly of a tripeptide into a functional coating that resists fouling . Chemical Communications . 50 . 76 . 11154–11157 . October 2014 . 25110984 . 10.1039/C4CC03578J .
  21. Fujii Y, Shibuya T, Yasuda T. L-3,4-Dihydroxyphenylalanine as an Allelochemical Candidate from Mucuna pruriens (L.) DC. var. utilis . Agricultural and Biological Chemistry . 55 . 2 . 617–618 . 1991 . 10.1080/00021369.1991.10870627 .
  22. Hsieh EJ, Liao SW, Chang CY, Tseng CH, Wang SL, Grillet L. L-DOPA induces iron accumulation in roots of Ipomoea aquatica and Arabidopsis thaliana in a pH-dependent manner . Botanical Studies . 64 . 24 . 617–618 . 2023 . 37620733 . 10449704 . 10.1186/s40529-023-00396-7 . free . 2023BotSt..64...24H .

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