D-penicillamine metabolism in neurodegenerative diseases: an in vivo/in vitro sulphydryl methylation study.
1. D-Penicillamine (125 mg) was administered orally to control (healthy volunteers), Parkinson's and Motor Neurone Disease patients following an overnight fast. 2. Blood was collected at 08:00 h for the preparation of red blood cell membranes used in the in vitro S-methylation studies. Urine was collected from 08:00 to 16:00 h and analysed for D-penicillamine and its metabolites. 3. Metabolism occurred via S-methylation, N-acetylation and disulphide formation. Both the Parkinson's and Motor Neurone Disease patients excreted significantly higher median levels of S-methyl-D-penicillamine in the urine than the controls (177 and 209% more for the Parkinson's and Motor Neurone Disease patients respectively). 4. The in vitro and in vivo production of S-methyl-D-pencillamine was highly correlated in the control (rs = 0.936), Parkinson's (0.986) and Motor Neurone Disease (0.752) populations.
Peters
L
L
Faculty of Applied Sciences, University of the West of England, Bristol, UK.
Steventon
G B
GB
Green
S
S
Sturman
S
S
Waring
R H
RH
Williams
A C
AC
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004910:Erythrocyte Membrane / Q000201:enzymology; D005260:Female; D006801:Humans; D008297:Male; D008745:Methylation; D008780:Methyltransferases / Q000097:blood; D008875:Middle Aged; D016472:Motor Neuron Disease / Q000378:metabolism*; D010300:Parkinson Disease / Q000378:metabolism*; D010396:Penicillamine / Q000378:metabolism*; D013438:Sulfhydryl Compounds / Q000378:metabolism*
D013438:Sulfhydryl Compounds; D008780:Methyltransferases; C022742:thiol S-methyltransferase; D010396:Penicillamine