S-methylation of captopril. Demonstration of captopril thiol methyltransferase activity in human erythrocytes and enzyme distribution in rat tissues.
The presence of a methyltransferase enzyme in human red blood cells (RBCs) capable of S-methylation of captopril is described. The apparent Michaelis-Menten (Km) constant for captopril was 0.5 mM and the maximum velocity (Vmax) was 0.391 pmoles S-methylcaptopril (mg protein)-1 min-1. There is some evidence presented to show that S-methylcaptopril inhibited its own formation with a ki value of 5.81 mM. Captopril thiol methyltransferase activity was also examined in rat tissues and was found to be present in all tissue studied. Subcellular localisation studies in rat liver suggest that the enzyme was microsomal in origin. The order of activity was liver greater than heart greater than spleen greater than lung greater than kidney much greater than RBC (rat). This tissue distribution was quite different from previous studies using other thiol substrates and is consistent with more than one form of thiol methyltransferase enzyme in tissues.
D000818:Animals; D002216:Captopril / Q000378:metabolism*; D002855:Chromatography, Thin Layer; D004912:Erythrocytes / Q000201:enzymology*; D005260:Female; D006801:Humans; D008297:Male; D008745:Methylation; D008780:Methyltransferases / Q000378:metabolism*; D011392:Proline / Q000031:analogs & derivatives*; D051381:Rats; D011919:Rats, Inbred Strains; D013347:Subcellular Fractions / Q000201:enzymology; D014018:Tissue Distribution
D011392:Proline; D002216:Captopril; D008780:Methyltransferases; C022742:thiol S-methyltransferase