D-ASPARTATE CONTENT OF ERYTHROCYTE-MEMBRANE PROTEINS IS DECREASED IN UREMIA - IMPLICATIONS FOR THE REPAIR OF DAMAGED PROTEINS

The authors of this article have demonstrated that erythrocytes from p atients affected by either chronic renal failure or ESRD, conditions a ssociated with erythrocyte membrane disorders, show reduced levels of methyl esterified membrane proteins because of elevated S-adenosylhomo cysteine concentration. The enzyme proteine L-isospartyl (D-aspartyl) O-methyltransferase, responsible for the bulk of this methyl esterific ation, is implicated in the repair of proteins containing isomerized a nd racemized aspartyl residues, which arise from L-asparaginyl and L-a spartyl residues. The presence of these altered residues, spontaneousl y generated during protein aging, can adversely affect protein functio n. The amount of D- and L-aspartyl residues (and their isomerized deri vatives) in erythrocyte membranes from hemodialysis patients was deter mined. The total level of D-aspartyl derivatives (D-Asx) actually was found to be lower than in controls. In contrast, neither the abundance of several other amino acids, nor of total non-Asx D-amino acids, dif fers between patients and controls. Mathematical simulation of relevan t reactions supports the hypothesis that these effects reflect the les sening of the normal D-isoaspartyl residue accumulation that occurs as a side reaction in the methyltransferase-induced repair process. This evidence is the first that D-Asx content is influenced in vivo by L-i soaspartyl (D-aspartyl) O-methyltransferase activity and can be signif icantly altered in a disease where this activity is inhibited, thus re presenting a red flag in a disrupted circuit.