'''{{sm|l}}-DOPA''', also known as '''{{sm|l}}-3,4-dihydroxyphenylalanine''' and used medically as '''levodopa''', is made and used as part of the normal [[biology]] of some plants<ref name="JAMANeuro">{{cite journal | vauthors = Cohen PA, Avula B, Katragunta K, Khan I | title = Levodopa Content of Mucuna pruriens Supplements in the NIH Dietary Supplement Label Database | journal = JAMA Neurology | volume = 79 | issue = 10 | pages = 1085–1086 | date = October 2022 | pmid = 35939305 | doi = 10.1001/jamaneurol.2022.2184 | pmc = 9361182 }}</ref> and animals, including humans. Humans, as well as a portion of the other animals that utilize {{sm|l}}-DOPA, make it via [[biosynthesis]] from the [[amino acid]] [[L-tyrosine|{{sm|l}}-tyrosine]].
'''{{sm|l}}-DOPA''', also known as '''{{sm|l}}-3,4-dihydroxyphenylalanine''' and used medically as '''levodopa''', is made and used as part of the normal [[biology]] of some plants<ref name="JAMANeuro">{{cite journal | vauthors = Cohen PA, Avula B, Katragunta K, Khan I | title = Levodopa Content of Mucuna pruriens Supplements in the NIH Dietary Supplement Label Database | journal = JAMA Neurology | volume = 79 | issue = 10 | pages = 1085–1086 | date = October 2022 | pmid = 35939305 | doi = 10.1001/jamaneurol.2022.2184 | pmc = 9361182 }}</ref> and animals, including humans. Humans, as well as a portion of the other animals that utilize {{sm|l}}-DOPA, make it via [[biosynthesis]] from the [[amino acid]] [[L-tyrosine|{{sm|l}}-tyrosine]].
{{sm|l}}-DOPA is the [[precursor (chemistry)|precursor]] to the [[neurotransmitter]]s [[dopamine]], [[norepinephrine]] (noradrenaline), and [[epinephrine]] (adrenaline), which are collectively known as [[catecholamine]]s. Furthermore, {{sm|l}}-DOPA itself mediates [[Neurotrophic factors|neurotrophic factor]] release by the brain and [[central nervous system]].<ref>{{cite journal | vauthors = Lopez VM, Decatur CL, Stamer WD, Lynch RM, McKay BS | title = L-DOPA is an endogenous ligand for OA1 | journal = PLOS Biology | volume = 6 | issue = 9 | pages = e236 | date = September 2008 | pmid = 18828673 | pmc = 2553842 | doi = 10.1371/journal.pbio.0060236 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Hiroshima Y, Miyamoto H, Nakamura F, Masukawa D, Yamamoto T, Muraoka H, Kamiya M, Yamashita N, Suzuki T, Matsuzaki S, Endo I, Goshima Y | title = The protein Ocular albinism 1 is the orphan GPCR GPR143 and mediates depressor and bradycardic responses to DOPA in the nucleus tractus solitarii | journal = British Journal of Pharmacology | volume = 171 | issue = 2 | pages = 403–14 | date = January 2014 | pmid = 24117106 | pmc = 3904260 | doi = 10.1111/bph.12459 }}</ref> In some plant families (of the order [[Caryophyllales]]), {{sm|l}}-DOPA is the central precursor of a biosynthetic pathway that produces a class of pigments called [[betalain]]s.<ref>{{cite journal |vauthors= Polturak G, Breitel D, Grossman N, Sarrion-Perdigones A, Weithorn E, Pliner M, Orzaez D, Granell A, Rogachev I, Aharoni A |title=Elucidation of the first committed step in betalain biosynthesis enables the heterologous engineering of betalain pigments in plants |journal= New Phytol |volume=210 |issue=1 |pages= 269–283 |year=2016 |doi=10.1111/nph.13796 |doi-access=free |pmid=26683006 |bibcode=2016NewPh.210..269P }}</ref>
{{sm|l}}-DOPA is the [[precursor (chemistry)|precursor]] to the [[neurotransmitter]]s [[dopamine]], [[norepinephrine]] (noradrenaline), and [[epinephrine]] (adrenaline), which are collectively known as [[catecholamine]]s. Furthermore, {{sm|l}}-DOPA itself mediates [[Neurotrophic factors|neurotrophic factor]] release by the brain and [[central nervous system]].<ref>{{cite journal | vauthors = Lopez VM, Decatur CL, Stamer WD, Lynch RM, McKay BS | title = L-DOPA is an endogenous ligand for OA1 | journal = PLOS Biology | volume = 6 | issue = 9 | pages = e236 | date = September 2008 | pmid = 18828673 | pmc = 2553842 | doi = 10.1371/journal.pbio.0060236 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Hiroshima Y, Miyamoto H, Nakamura F, Masukawa D, Yamamoto T, Muraoka H, Kamiya M, Yamashita N, Suzuki T, Matsuzaki S, Endo I, Goshima Y | title = The protein Ocular albinism 1 is the orphan GPCR GPR143 and mediates depressor and bradycardic responses to DOPA in the nucleus tractus solitarii | journal = British Journal of Pharmacology | volume = 171 | issue = 2 | pages = 403–14 | date = January 2014 | pmid = 24117106 | pmc = 3904260 | doi = 10.1111/bph.12459 }}</ref> In some plant families (of the order [[Caryophyllales]]), {{sm|l}}-DOPA is the central precursor of a biosynthetic pathway that produces a class of pigments called [[betalain]]s.<ref>{{cite journal |vauthors= Polturak G, Breitel D, Grossman N, Sarrion-Perdigones A, Weithorn E, Pliner M, Orzaez D, Granell A, Rogachev I, Aharoni A |title=Elucidation of the first committed step in betalain biosynthesis enables the heterologous engineering of betalain pigments in plants |journal= New Phytol |volume=210 |issue=1 |pages= 269–283 |year=2016 |doi=10.1111/nph.13796 |doi-access=free |pmid=26683006 |bibcode=2016NewPh.210..269P |hdl=10251/87415 |hdl-access=free }}</ref>
{{sm|l}}-DOPA can be manufactured and in its pure form is sold as a [[drug]] with the {{Abbrlink|INN|International Nonproprietary Name}} ''[[levodopa]]''. As a drug, it is used in the [[therapy|treatment]] of [[Parkinson's disease]] and [[dopamine-responsive dystonia]], as well as [[restless leg syndrome]].<ref>{{cite journal |last1=Scholz |first1=Hanna |last2=Trenkwalder |first2=Claudia |last3=Kohnen |first3=Ralf |last4=Kriston |first4=Levente |last5=Riemann |first5=Dieter |last6=Hornyak |first6=Magdolna |title=Levodopa for the treatment of restless legs syndrome |journal=Cochrane Database of Systematic Reviews |date=15 February 2011 |volume=2011 |issue=5 |pages=CD005504 |doi=10.1002/14651858.CD005504.pub2 |pmid=21328278 |s2cid=196338172 |pmc=8889887 }}</ref>
{{sm|l}}-DOPA can be manufactured and in its pure form is sold as a [[drug]] with the {{Abbrlink|INN|International Nonproprietary Name}} ''[[levodopa]]''. As a drug, it is used in the [[therapy|treatment]] of [[Parkinson's disease]] and [[dopamine-responsive dystonia]], as well as [[restless leg syndrome]].<ref>{{cite journal |last1=Scholz |first1=Hanna |last2=Trenkwalder |first2=Claudia |last3=Kohnen |first3=Ralf |last4=Kriston |first4=Levente |last5=Riemann |first5=Dieter |last6=Hornyak |first6=Magdolna |title=Levodopa for the treatment of restless legs syndrome |journal=Cochrane Database of Systematic Reviews |date=15 February 2011 |volume=2011 |issue=5 |pages=CD005504 |doi=10.1002/14651858.CD005504.pub2 |pmid=21328278 |s2cid=196338172 |pmc=8889887 }}</ref>
<templatestyles src="smallcaps/styles.css"/>l-DOPA, also known as <templatestyles src="smallcaps/styles.css"/>l-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 <templatestyles src="smallcaps/styles.css"/>l-DOPA, make it via biosynthesis from the amino acid<templatestyles src="smallcaps/styles.css"/>l-tyrosine.
<templatestyles src="smallcaps/styles.css"/>l-DOPA has a counterpart with opposite chirality, <templatestyles src="smallcaps/styles.css"/>d-DOPA. As is true for many molecules, the human body produces only one of these isomers (the <templatestyles src="smallcaps/styles.css"/>l-DOPA form). The enantiomeric purity of <templatestyles src="smallcaps/styles.css"/>l-DOPA may be analyzed by determination of the optical rotation or by chiral thin-layer chromatography.[6]
Template:Phenylalanine biosynthesis
<templatestyles src="smallcaps/styles.css"/>l-DOPA is produced from the amino acid <templatestyles src="smallcaps/styles.css"/>l-tyrosine by the enzyme tyrosine hydroxylase. <templatestyles src="smallcaps/styles.css"/>l-DOPA can act as an <templatestyles src="smallcaps/styles.css"/>l-tyrosine mimetic and be incorporated into proteins by mammalian cells in place of <templatestyles src="smallcaps/styles.css"/>l-tyrosine, generating protease-resistant and aggregate-prone proteinsin vitro and may contribute to neurotoxicity with chronic <templatestyles src="smallcaps/styles.css"/>l-DOPA administration.[7]
It is also the precursor for the monoamine or catecholamine neurotransmitters dopamine, norepinephrine (noradrenaline), and epinephrine (adrenaline). Dopamine is formed by the decarboxylation of <templatestyles src="smallcaps/styles.css"/>l-DOPA by aromatic <templatestyles src="smallcaps/styles.css"/>l-amino acid decarboxylase (AADC).
<templatestyles src="smallcaps/styles.css"/>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 <templatestyles src="smallcaps/styles.css"/>l-DOPA administration in patients with Parkinson's disease or in the rare cases of patients with AADC enzyme deficiency.[8]
<templatestyles src="smallcaps/styles.css"/>l-Phenylalanine, <templatestyles src="smallcaps/styles.css"/>l-tyrosine, and <templatestyles src="smallcaps/styles.css"/>l-DOPA are all precursors to the biological pigmentmelanin. The enzyme tyrosinasecatalyzes the oxidation of <templatestyles src="smallcaps/styles.css"/>l-DOPA to the reactive intermediate dopaquinone, which reacts further, eventually leading to melanin oligomers. In addition, tyrosinase can convert tyrosine directly to <templatestyles src="smallcaps/styles.css"/>l-DOPA in the presence of a reducing agent such as ascorbic acid.[9]
History
<templatestyles src="smallcaps/styles.css"/>l-DOPA was first isolated from the seeds of the Vicia faba (broad bean) plant in 1913 by Swiss biochemist Markus Guggenheim.[10]
The 2001 Nobel Prize in Chemistry was also related to <templatestyles src="smallcaps/styles.css"/>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 <templatestyles src="smallcaps/styles.css"/>l-DOPA.[11][12][13]
File:L-dopaSyn.svgSynthesis of <templatestyles src="smallcaps/styles.css"/>l-DOPA via hydrogenation with C2-symmetric diphosphine.
Other organisms
Marine adhesion
<templatestyles src="smallcaps/styles.css"/>l-DOPA is a key compound in the formation of marine adhesive proteins, such as those found in mussels.[14][15] It is believed to be responsible for the water-resistance and rapid curing abilities of these proteins. <templatestyles src="smallcaps/styles.css"/>l-DOPA may also be used to prevent surfaces from fouling by bonding antifouling polymers to a susceptible substrate.[16] The versatile chemistry of <templatestyles src="smallcaps/styles.css"/>l-DOPA can be exploited in nanotechnology.[17] For example, DOPA-containing self-assembling peptides were found to form functional nanostructures, adhesives and gels.[18][19][20][21]
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.[22] Its effect is strongly dependent on the pH and the reactivity of iron in the soil.[23] L-DOPA can also be found in cephalopod ink.[24]
Use as a medication and supplement
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