Inhibition of protein carboxyl methylation by S-adenosyl-L-homocysteine in intact erythrocytes. Physiological consequences.
S-Adenosyl-L-homocysteine was used to inhibit the methylation of carboxylic acid residues of membrane proteins in intact human erythrocytes. Incubation of erythrocytes for 24 h with 5 mM each of adenosine and L-homocysteine resulted in the intracellular accumulation of S-adenosyl-L-homocysteine and substantially inhibited membrane protein carboxyl methylation. From the degree of inhibition and from the observed turnover of methylated proteins, we estimate that the number of protein methyl esters in cells incubated with adenosine and L-homocysteine for 20 h is less than 20% that of cells incubated without these inhibitors. No significant differences in the physical deformability properties of the membrane of these hypomethylated cells were detected. However, there was a small but significant (p less than 0.001) increase in the amount of membrane protein D-aspartyl residues in these cells compared to control cells. These observations are consistent with the hypothesis that methylation of membrane proteins at D-aspartyl residues may result in the selective removal or repair of these uncommon residues.
D000241:Adenosine / Q000494:pharmacology; D001224:Aspartic Acid / Q000097:blood; D004910:Erythrocyte Membrane / Q000187:drug effects; D004912:Erythrocytes / Q000201:enzymology*; D006710:Homocysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D008565:Membrane Proteins / Q000097:blood*; D008715:Methionine / Q000031:analogs & derivatives / Q000378:metabolism; D008745:Methylation; D026601:Protein D-Aspartate-L-Isoaspartate Methyltransferase; D011496:Protein Methyltransferases / Q000097:blood*; D011499:Protein Processing, Post-Translational; D012435:S-Adenosylhomocysteine / Q000494:pharmacology*; D012436:S-Adenosylmethionine / Q000378:metabolism
D008565:Membrane Proteins; D006710:Homocysteine; D001224:Aspartic Acid; D012436:S-Adenosylmethionine; D012435:S-Adenosylhomocysteine; D008715:Methionine; C038344:methionine methyl ester; C007957:homocysteine thiolactone; D011496:Protein Methyltransferases; D026601:Protein D-Aspartate-L-Isoaspartate Methyltransferase; D000241:Adenosine