l-DOPA, also known asl-3,4-dihydroxyphenylalanine and used medically aslevodopa, is made and used as part of the normalbiology of some plants[2] and animals, including humans. Humans, as well as a portion of the other animals that utilizel-DOPA, make it viabiosynthesis from theamino acidl-tyrosine.
l-DOPA has a counterpart with oppositechirality,d-DOPA. As is true for many molecules, the human body produces only one of theseisomers (thel-DOPA form). Theenantiomeric purity ofl-DOPA may be analyzed by determination of the optical rotation or by chiralthin-layer chromatography.[7]
l-DOPA is produced from the amino acidl-tyrosine by the enzymetyrosine hydroxylase.l-DOPA can act as anl-tyrosine mimetic and be incorporated into proteins by mammalian cells in place ofl-tyrosine, generatingprotease-resistant andaggregate-prone proteinsin vitro and may contribute toneurotoxicity with chronicl-DOPA administration.[11]It is also the precursor for themonoamine orcatecholamine neurotransmitters dopamine, norepinephrine (noradrenaline), and epinephrine (adrenaline). Dopamine is formed by the decarboxylation ofl-DOPA byaromaticl-amino acid decarboxylase (AADC).
l-DOPA can be directly metabolized bycatechol-O-methyl transferase to3-O-methyldopa, and then further tovanillactic acid. This metabolic pathway is nonexistent in the healthy body, but becomes important after peripherall-DOPA administration in patients with Parkinson's disease or in the rare cases of patients with AADC enzyme deficiency.[12]
l-Phenylalanine,l-tyrosine, andl-DOPA are all precursors to the biologicalpigmentmelanin. The enzymetyrosinasecatalyzes theoxidation ofl-DOPA to the reactive intermediatedopaquinone, which reacts further, eventually leading to melaninoligomers. In addition,tyrosinase can convert tyrosine directly tol-DOPA in the presence of a reducing agent such asascorbic acid.[13]
l-DOPA was first isolated from the seeds of theVicia faba (broad bean) plant in 1913 by Swiss biochemist Markus Guggenheim.[14]
The 2001Nobel Prize in Chemistry was also related tol-DOPA: the Nobel Committee awarded one-quarter of the prize toWilliam S. Knowles for his work on chirally catalysedhydrogenation reactions, the most noted example of which was used for the synthesis ofl-DOPA.[15][16][17]
l-DOPA is a keycompound in the formation ofmarine adhesive proteins, such as those found inmussels.[18][19] 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 susceptiblesubstrate.[20] The versatile chemistry ofl-DOPA can be exploited in nanotechnology.[21] For example, DOPA-containing self-assembling peptides were found to form functional nanostructures, adhesives and gels.[22][23][24][25]
In plants,L-DOPA functions as anallelochemical which inhibits the growth of certain species, and is produced and secreted by a few legume species such as the broad beanVicia faba and the velvet beanMucuna pruriens.[26] Its effect is strongly dependent on the pH and the reactivity of iron in the soil.[27]L-DOPA can also be found incephalopod ink.[28]
^Martens J, Günther K, Schickedanz M (1986). "Resolution of Optical Isomers by Thin-Layer Chromatography: Enantiomeric Purity of Methyldopa".Arch. Pharm.319 (6):572–574.doi:10.1002/ardp.19863190618.S2CID97903386.
^Lindemann L, Hoener MC (May 2005). "A renaissance in trace amines inspired by a novel GPCR family".Trends in Pharmacological Sciences.26 (5):274–281.doi:10.1016/j.tips.2005.03.007.PMID15860375.
^Wang X, Li J, Dong G, Yue J (February 2014). "The endogenous substrates of brain CYP2D".European Journal of Pharmacology.724:211–218.doi:10.1016/j.ejphar.2013.12.025.PMID24374199.
^Knowles WS (March 1986). "Application of organometallic catalysis to the commercial production of L-DOPA".Journal of Chemical Education.63 (3): 222.Bibcode:1986JChEd..63..222K.doi:10.1021/ed063p222.
^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.S2CID136967853.
^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.PMID25110984.
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