Is There a Function for Protein Carboxylmethylation in the Nervous System?

Abstract

The functional aspects of protein carboxylmethylation in eucaryotic cells have remained enigmatic. Some of the major issues which obscure the possible role of this enzyme are 1) the nature and specificity of relevant in vivo protein substrates; 2) the stoichiometry of protein carboxylmethylation and 3) the rapid hydrolysis of carboxylmethylesters under conditions of neutral and basic pH (Billingsley and Lovenberg, 1985). Thus, two major schools of thought have arisen which attempt to address these issues-the functionalists, who look for revelant substrates which may be regulated by rapid carboxylmethylation, and the structuralists, who suggest that protein carboxylmethylation recognizes and/or repairs either reacemized aspartyl (Terwilliger and Clarke, 1981; McFadden and Clarke, 1982; Murray and Clarke, 1984) or beta isopeptide links (Aswad, 1984; O’Connor, et al., 1984) in a wide range of substrates. We will present evidence which suggests a possible functional role for protein-0-carboxylmethyltransferase (PCM; E.C.2.1.1.24) in nervous tissue based on the following findings.