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Impaired transmethylation potential in Parkinson's disease patients treated with L-Dopa.
Neurosci Lett. 2010 Jan 14; 468(3):287-91.NL

Abstract

Hyperhomocysteinaemia was reported in patients with Parkinson's disease (PD) treated with l-Dopa. The increase in plasma concentration of this sulfur compound arises from the massive methylation of the drug operated by the enzyme catechol-O-methyltransferase (COMT), which acts as a powerful sink of methyl groups. The contemporary occurrence of C677T polymorphism in homozygosity, leading to a temperature-labile variant of the MTHFR enzyme, induces an even more marked increase in tHcy. Here we show that l-Dopa administration in hyperhomocysteinemic PD patients is able to lower intracellular concentration of S-Adenosylmethionine (AdoMet) in erythrocytes (RBC), while the occurrence of hyperhomocysteinaemia causes a significant increase in S-Adenosylhomocysteine (AdoHcy) level. In patients with PD treated with l-Dopa and hyperhomocysteinemic, the remarkable decrease in AdoMet and the concurrent increase in AdoHcy concentration both contribute to significantly lower the transmethylation potential ([AdoMet]/[AdoHcy]), a useful index of the effectiveness of methyl group transfer by methyltransferases. This decrease could indeed contribute to partly attenuate, through a self-limiting kinetic mechanism, the tendency of developing drug resistance, partly mediated in these patients by COMT upregulation. Our results also support the conclusion that COMT inhibitors (entacapone or tolcapone), when administered in PD patients treated with l-Dopa, may potentiate the endogenous AdoHcy-dependent COMT inhibition mechanism already operative in a variable fashion.

Authors+Show Affiliations

Department of Biochemistry and Biophysics, Second University of Naples, Italy.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19909787

Citation

De Bonis, Maria Luigia, et al. "Impaired Transmethylation Potential in Parkinson's Disease Patients Treated With L-Dopa." Neuroscience Letters, vol. 468, no. 3, 2010, pp. 287-91.
De Bonis ML, Tessitore A, Pellecchia MT, et al. Impaired transmethylation potential in Parkinson's disease patients treated with L-Dopa. Neurosci Lett. 2010;468(3):287-91.
De Bonis, M. L., Tessitore, A., Pellecchia, M. T., Longo, K., Salvatore, A., Russo, A., Ingrosso, D., Zappia, V., Barone, P., Galletti, P., & Tedeschi, G. (2010). Impaired transmethylation potential in Parkinson's disease patients treated with L-Dopa. Neuroscience Letters, 468(3), 287-91. https://doi.org/10.1016/j.neulet.2009.11.014
De Bonis ML, et al. Impaired Transmethylation Potential in Parkinson's Disease Patients Treated With L-Dopa. Neurosci Lett. 2010 Jan 14;468(3):287-91. PubMed PMID: 19909787.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Impaired transmethylation potential in Parkinson's disease patients treated with L-Dopa. AU - De Bonis,Maria Luigia, AU - Tessitore,Alessandro, AU - Pellecchia,Maria Teresa, AU - Longo,Katia, AU - Salvatore,Anna, AU - Russo,Antonio, AU - Ingrosso,Diego, AU - Zappia,Vincenzo, AU - Barone,Paolo, AU - Galletti,Patrizia, AU - Tedeschi,Gioacchino, Y1 - 2009/11/10/ PY - 2009/07/25/received PY - 2009/11/04/revised PY - 2009/11/05/accepted PY - 2009/11/14/entrez PY - 2009/11/17/pubmed PY - 2010/4/7/medline SP - 287 EP - 91 JF - Neuroscience letters JO - Neurosci Lett VL - 468 IS - 3 N2 - Hyperhomocysteinaemia was reported in patients with Parkinson's disease (PD) treated with l-Dopa. The increase in plasma concentration of this sulfur compound arises from the massive methylation of the drug operated by the enzyme catechol-O-methyltransferase (COMT), which acts as a powerful sink of methyl groups. The contemporary occurrence of C677T polymorphism in homozygosity, leading to a temperature-labile variant of the MTHFR enzyme, induces an even more marked increase in tHcy. Here we show that l-Dopa administration in hyperhomocysteinemic PD patients is able to lower intracellular concentration of S-Adenosylmethionine (AdoMet) in erythrocytes (RBC), while the occurrence of hyperhomocysteinaemia causes a significant increase in S-Adenosylhomocysteine (AdoHcy) level. In patients with PD treated with l-Dopa and hyperhomocysteinemic, the remarkable decrease in AdoMet and the concurrent increase in AdoHcy concentration both contribute to significantly lower the transmethylation potential ([AdoMet]/[AdoHcy]), a useful index of the effectiveness of methyl group transfer by methyltransferases. This decrease could indeed contribute to partly attenuate, through a self-limiting kinetic mechanism, the tendency of developing drug resistance, partly mediated in these patients by COMT upregulation. Our results also support the conclusion that COMT inhibitors (entacapone or tolcapone), when administered in PD patients treated with l-Dopa, may potentiate the endogenous AdoHcy-dependent COMT inhibition mechanism already operative in a variable fashion. SN - 1872-7972 UR - https://www.unboundmedicine.com/medline/citation/19909787/Impaired_transmethylation_potential_in_Parkinson's_disease_patients_treated_with_L_Dopa_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0304-3940(09)01480-3 DB - PRIME DP - Unbound Medicine ER -