L-DOPA

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Template:Sm-DOPA, also known as Template:Sm-3,4-dihydroxyphenylalanine and used medically as levodopa, is made and used as part of the normal biology of some plants<ref name="JAMANeuro">Template:Cite journal</ref> and animals, including humans. Humans, as well as a portion of the other animals that utilize Template:Sm-DOPA, make it via biosynthesis from the amino acid [[L-tyrosine|Template:Sm-tyrosine]].

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

Template:Sm-DOPA can be manufactured and in its pure form is sold as a drug with the Template:Abbrlink levodopa. As a drug, it is used in the treatment of Parkinson's disease and dopamine-responsive dystonia, as well as restless leg syndrome.<ref>Template:Cite journal</ref>

Template:Sm-DOPA has a counterpart with opposite chirality, [[D-DOPA|Template:Sm-DOPA]]. As is true for many molecules, the human body produces only one of these isomers (the Template:Sm-DOPA form). The enantiomeric purity of Template:Sm-DOPA may be analyzed by determination of the optical rotation or by chiral thin-layer chromatography.<ref>Template:Cite journal</ref>

Biological role

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

Template:Sm-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 Template:Sm-DOPA administration in patients with Parkinson's disease or in the rare cases of patients with AADC enzyme deficiency.<ref name="pmid1281049">Template:Cite journal</ref>

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

History

Template:Sm-DOPA was first isolated from the seeds of the Vicia faba (broad bean) plant in 1913 by Swiss biochemist Markus Guggenheim.<ref>Template:Cite journal</ref>

The 2001 Nobel Prize in Chemistry was also related to Template:Sm-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 Template:Sm-DOPA.<ref>Template:Cite journal</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref>Template:Cite journal</ref>

File:L-dopaSyn.svg

Synthesis of Template:Sm-DOPA via hydrogenation with C₂-symmetric diphosphine.

Other organisms

Marine adhesion

Template:Sm-DOPA is a key compound in the formation of marine adhesive proteins, such as those found in mussels.<ref>Template:Cite journal</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> It is believed to be responsible for the water-resistance and rapid curing abilities of these proteins. Template:Sm-DOPA may also be used to prevent surfaces from fouling by bonding antifouling polymers to a susceptible substrate.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> The versatile chemistry of Template:Sm-DOPA can be exploited in nanotechnology.<ref>Template:Cite journal</ref> For example, DOPA-containing self-assembling peptides were found to form functional nanostructures, adhesives and gels.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref><ref>Template:Cite journal</ref><ref>Template:Cite journal</ref>

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.<ref>Template:Cite journal</ref> Its effect is strongly dependent on the pH and the reactivity of iron in the soil.<ref>Template:Cite journal</ref> L-DOPA can also be found in cephalopod ink.<ref>Template:Cite journal</ref>

Use as a medication and supplement

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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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