Decrease of methionine and S-adenosylmethionine and increase of homocysteine in treated patients with Parkinson's disease.
Levodopa is administered with dopa decarboxylase inhibitors (DDI) to prevent its peripheral degradation. This increases conversion of levodopa to 3-O-methyldopa (3-OMD) by catechol-O-methyltransferase (COMT). S-adenosylmethionine (SAM), which is synthesized from adenosine triphosphate and methionine (MET), serves as methyl donor for this O-metabolisation of levodopa with resulting conversion of SAM to total homocysteine (tHcy) via S-adenosylhomocysteine (SAH). Previous studies showed augmented plasma levels of tHcy in long-term levodopa/DDI-treated patients with Parkinson's disease (PP). Objective of this study was to compare MET, SAM, levodopa, 3-OMD, tHcy and SAH in plasma of 20 levodopa/DDI treated PP and corresponding controls. A significant decrease of MET respectively SAM and an increase of tHcy appeared in PP. SAH with its short half-life did not differ. Levodopa/DDI long-term treatment contributes to altered levels of substrates of the O-methylation cycle in PP.
Müller
T
T
Department of Neurology, St. Josef Hospital, Ruhr University Bochum, Gudrunstrasse 56, D-44791, Bochum, Germany. thomas.mueller@ruhr-uni-bochum.de
Woitalla
D
D
Hauptmann
B
B
Fowler
B
B
Kuhn
W
W
D000368:Aged; D000369:Aged, 80 and over; D000978:Antiparkinson Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D002318:Cardiovascular Diseases / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology; D004296:Dopa Decarboxylase / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D004347:Drug Interactions / Q000502:physiology; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D007980:Levodopa / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D008297:Male; D008715:Methionine / Q000097:blood*; D008875:Middle Aged; D010300:Parkinson Disease / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D012436:S-Adenosylmethionine / Q000097:blood*; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D000978:Antiparkinson Agents; D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D004791:Enzyme Inhibitors; D006710:Homocysteine; D007980:Levodopa; D012436:S-Adenosylmethionine; D008715:Methionine; D004296:Dopa Decarboxylase