The effect of D-penicillamine on protein-bound homocyst(e)ine in homocystinurics.
There is considerable evidence that homocystine has a direct damaging effect on vascular endothelium and other tissues. The demonstration of the existence of protein-bound homocyst(e)ine has strengthened this hypothesis. In an attempt to remove bound homocyst(e)ine, D-penicillamine was given to three patients with pyridoxine-nonresponsive homocystinuria. Before the clinical trial, it had been demonstrated that 0.1 mumole per ml concentration of D-penicillamine or cysteamine released approximately 50% of the homocyst(e)ine bound to plasma proteins in vitro. Oral D-penicillamine effectively reduced both free and plasma protein-bound homocyst(e)ine in homocystinurics from the second day of treatment. The homocystine excreted in the urine was mainly in the form of homocysteine-penicillamine disulfide. No mixed disulfide was detectable in the plasma, indicating an extremely high renal clearance. These observations suggested that oral D-penicillamine removed a considerable quantity of the bound homocyst(e)ine accumulated in the tissue proteins.
D000293:Adolescent; D000328:Adult; D001798:Blood Proteins / Q000378:metabolism; D005260:Female; D006710:Homocysteine / Q000097:blood*; D006711:Homocystine / Q000097:blood*; D006712:Homocystinuria / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D008297:Male; D010396:Penicillamine / Q000627:therapeutic use*; D011485:Protein Binding; D011736:Pyridoxine / Q000627:therapeutic use
D001798:Blood Proteins; D006710:Homocysteine; D006711:Homocystine; D010396:Penicillamine; D011736:Pyridoxine