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Pathway Description
Levodopa Metabolism Pathway
Homo sapiens
Metabolic Pathway
Created: 2022-04-26
Last Updated: 2023-10-25
Levodopa is an oral drug used in the management of Parkinson's disease, often in combination with carbidopa, as well as other conditions associated with parkinsonism.
It is a dopamine precursor and is used to synthesize dopamine in dopaminergic neurons. This supplemental dopamine performs the role that endogenous dopamine cannot due to a decrease of natural concentrations in Parkinson’s.
Levodopa is either converted to dopamine by aromatic-L-amino-acid decarboxylase or O-methylated to 3-O-methyldopa by catechol-O-methyltransferase. 3-O-methyldopa cannot be metabolized to dopamine. Once levodopa is converted to dopamine, it is converted to sulfated or glucuronidated metabolites, epinephrine E, or homovanillic acid through various metabolic processes. The primary metabolites are 3,4-dihydroxyphenylacetic acid (13-47%) and homovanillic acid (23-39%).
After 48 hours, 0.17% of an orally administered dose is recovered in stool, 0.28% is exhaled, and 78.4% is recovered in urine.
The common adverse effects of Levodopa treatment are nausea, dizziness, headache, and somnolence.
References
Levodopa Metabolism Pathway References
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Pubmed: 25073474
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Pubmed: 28018168
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Lundstrom K, Salminen M, Jalanko A, Savolainen R, Ulmanen I: Cloning and characterization of human placental catechol-O-methyltransferase cDNA. DNA Cell Biol. 1991 Apr;10(3):181-9. doi: 10.1089/dna.1991.10.181.
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Bertocci B, Miggiano V, Da Prada M, Dembic Z, Lahm HW, Malherbe P: Human catechol-O-methyltransferase: cloning and expression of the membrane-associated form. Proc Natl Acad Sci U S A. 1991 Feb 15;88(4):1416-20. doi: 10.1073/pnas.88.4.1416.
Pubmed: 1847521
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Ichinose H, Kurosawa Y, Titani K, Fujita K, Nagatsu T: Isolation and characterization of a cDNA clone encoding human aromatic L-amino acid decarboxylase. Biochem Biophys Res Commun. 1989 Nov 15;164(3):1024-30. doi: 10.1016/0006-291x(89)91772-5.
Pubmed: 2590185
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Pubmed: 1540578
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Pubmed: 3418353
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Pubmed: 3387449
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Pubmed: 8493892
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Pubmed: 14702039
Williams HJ, Bray N, Murphy KC, Cardno AG, Jones LA, Owen MJ: No evidence for allelic association between schizophrenia and a functional variant of the human dopamine beta-hydroxylase gene (DBH). Am J Med Genet. 1999 Oct 15;88(5):557-9.
Pubmed: 10490716
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Lamouroux A, Vigny A, Faucon Biguet N, Darmon MC, Franck R, Henry JP, Mallet J: The primary structure of human dopamine-beta-hydroxylase: insights into the relationship between the soluble and the membrane-bound forms of the enzyme. EMBO J. 1987 Dec 20;6(13):3931-7.
Pubmed: 3443096
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