cysteinylglycine and Parkinson-Disease

Exposure to free radicals influences synthesis, degradation and function of proteins, such as repulsive guidance molecule A. Decay of this protein is essential for neuronal maintenance and recovery. Levodopa elevates oxidative stress. Therefore levodopa may impact repulsive guidance molecule A metabolism. Objectives were to investigate plasma concentrations of repulsive guidance molecule A, levodopa, cysteine and cysteinyl-glycine before and 1 h after levodopa application in patients with Parkinson's disease. Cysteine and cysteinyl-glycine as biomarkers for oxidative stress exposure decreased, repulsive guidance molecule A and levodopa rose. Repulsive guidance molecule A remained unchanged in levodopa naïve patients, but particularly went up in patients on a prior chronic levodopa regimen. Decay of cysteine specifically cysteinyl-glycine results from an elevated glutathione generation with rising cysteine consumption respectively from the alternative glutathione transformation to its oxidized form glutathione disulfide after free radical scavenging. Repulsive guidance molecule A rise may inhibit physiologic mechanisms for neuronal survival.

Topics: Aged; Antiparkinson Agents; Carbidopa; Chromatography, High Pressure Liquid; Cysteine; Dipeptides; Drug Combinations; Female; GPI-Linked Proteins; Humans; Levodopa; Male; Middle Aged; Nerve Tissue Proteins; Oxidative Stress; Parkinson Disease; Pilot Projects

Homocysteine increase and glutathione derivative cysteinyl-glycine fall are indirect biomarkers for oxidative stress, for instance due to dopamine D. To investigate the influence of the D. Patients received 100 mg levodopa, 4 mg rotigotine or placebo. Cysteinyl-glycine and homocysteine were measured every 30 min over three hours.. Homocysteine rose during levodopa- and placebo administration. Rotigotine had no effect. Cysteine-glycine only increased after placebo- but not after levodopa- or rotigotine.. Homocysteine elevation results from hepatic and gastrointestinal methylation processes. Transdermal rotigotine circumvents these methylation locations. Turnover of segregated alkyl residuals from rotigotine serves as methyl group donors, which counteract homocysteine increment. The placebo-related cysteinyl-glycine increase results from reduced free radical exposure. Low levodopa dosing and antioxidants in the rotigotine patch matrix prevented cysteinyl-glycine fall.

Topics: Aged; Analysis of Variance; Chromatography, High Pressure Liquid; Dihydroxyphenylalanine; Dipeptides; Dopamine Agents; Electrochemical Techniques; Female; Homocysteine; Humans; Levodopa; Male; Middle Aged; Oxidative Stress; Parkinson Disease; Tetrahydronaphthalenes; Thiophenes; Time Factors; Tyrosine

Oxidative stress is influenced by the thiol homeostasis, which regulates the redox milieu via glutathione. Components of glutathione metabolism are cysteine and cysteinyl-glycine. Both substrates decay following levodopa application or dopamine-related oxidative stress. Objective was to investigate the impact of an acute levodopa application with and without catechol-O-methyltransferase inhibitor on cysteine- and cysteinyl-glycine plasma levels. On two investigation days, 13 patients with Parkinson's disease took one retarded release 200-mg levodopa/50 mg carbidopa-containing tablet or one 150-mg levodopa/50-mg carbidopa/200-mg entacapone formulation under standardized conditions. Levodopa, 3-O-methyldopa, cysteine and cysteinyl-glycine were measured at baseline, 80 and 140 min following levodopa administration. Cysteine and cysteinyl-glycine similarly decreased, levodopa was nearly equal during both conditions. Entacapone lowered 3-O-methyldopa. Cysteine decay may be due to an elevated glutathione generation, which consumes cysteine. Cysteinyl-glycine decrease results from the alternative glutathione transformation to its oxidized form glutathione dissulfide after free radical scavenging.

Topics: Aged; Analysis of Variance; Antiparkinson Agents; Carbidopa; Catechol O-Methyltransferase; Catechols; Chromatography, Reverse-Phase; Cysteine; Dipeptides; Drug Delivery Systems; Female; Humans; Levodopa; Male; Methyldopa; Middle Aged; Nitriles; Parkinson Disease; Time Factors

Oxidative stress is influenced by the thiol homeostasis, which determines the redox milieu. One of its components is Cysteinyl-glycine (Cys-Gly) generation, as its metabolic precursor is the free radicals scavenging glutathione. Levodopa is under suspicion to promote oxidative stress via the turnover of its metabolite dopamine in abundant mitochondria. Objective was to investigate the impact of levodopa on Cys-Gly plasma metabolism. Fifteen patients with Parkinson's disease orally took one 200-mg levodopa/50-mg carbidopa (CD) containing tablet. Levodopa, its derivative 3-O-methyldopa (3-OMD), and free Cys-Gly were measured at baseline, 60 and 120 min following levodopa/CD administration. Cys-gly concentrations decreased, levodopa and 3-OMD levels increased. Inverse relationships appeared between computed differences of Cys-gly and 3-OMD bioavailability. We conclude that Cys-Gly decline is related to levodopa metabolism to 3-OMD. Cys-Gly decay may result from the alternative transformation of glutathione to its oxidized form glutathione dissulfide as consequence of free radical scavenging.

Topics: Analysis of Variance; Antiparkinson Agents; Carbidopa; Dipeptides; Female; Humans; Levodopa; Male; Oxidative Stress; Parkinson Disease; Tyrosine

Significantly elevated plasma levels of homocysteine, but not cysteine and cysteinylglycine, were found in treated parkinsonian patients compared to controls. Elevated levels of homocysteine may be either caused by an unknown endogenous metabolic disturbance or by antiparkinsonian treatment, because no association to severity or duration of disease was found. Based on the results of this study one may speculate that homocysteine may be an independent risk factor for vascular disease in Parkinson's disease.

Topics: Aged; Aged, 80 and over; Case-Control Studies; Cysteine; Dipeptides; Female; Homocysteine; Humans; Male; Middle Aged; Parkinson Disease; Risk Factors