ENZYMATIC METHYL ESTERIFICATION OF ERYTHROCYTE-MEMBRANE PROTEINS IS IMPAIRED IN CHRONIC-RENAL-FAILURE - EVIDENCE FOR HIGH-LEVELS OF THE NATURAL INHIBITOR S-ADENOSYLHOMOCYSTEINE

The enzyme protein carboxyl methyltransferase type II has been recentl y shown to play a crucial role in the repair of damaged proteins. S-ad enosylmethionine (AdoMet) is the methyl donor of the reaction, and its demethylated product, S-adenosylhomocysteine (AdoHcy), is the natural inhibitor of this reaction, as well as of most AdoMet-dependent methy lations. We examined erythrocyte membrane protein methyl esterificatio n in chronic renal failure (CRF) patients on conservative treatment or hemodialyzed to detect possible alterations of the methylation patter n, in a condition where a state of disrupted red blood cell function i s present. We observed a significant reduction in membrane protein met hyl esterification in both groups, compared to control. The decrease w as particularly evident for cytoskeletal component ankyrin, which is k nown to be involved in membrane stability and integrity. Moreover, we observed a severalfold rise in AdoHcy levels, while AdoMet concentrati on was comparable to that detected in the control, resulting in a lowe r [AdoMet]/{AdoHcy] ratio (P < 0.001). Our findings show an impairment of this posttranslational modification of proteins, associated with h igh AdoHcy intracellular concentration in CRF. The data are consistent with the notion that, in CRF, structural damages accumulate in erythr ocyte membrane proteins, and are not adequately repaired.