REGIONAL DIFFERENCES IN PROTEIN CARBOXYMETHYLATION IN POSTMORTEM HUMAN BRAIN

1. The aim of this study was to determine the pattern of protein carbo xymethylation in different regions of the human brain. 2. The availabi lity of protein methylation sites was determined by measurement of the incorporation of methyl-H-3 groups into proteins isolated from postmo rtem brain tissue. The stability of protein carboxymethylation in post -mortem brain was determined by sampling post-mortem pig and human bra in tissue at intervals during the first 24 h after death. This method has previously been used to demonstrate that decreased protein carboxy methylation occurred in post-mortem pig brain when methionine synthase was inhibited. 3. There were no significant differences in the protei n carboxymethyltransferase activity in samples of pig brain obtained a t the time of death compared with that obtained when the same tissue w as maintained at room temperature for up to 24 h after death. Similarl y, there were no significant differences in the protein carboxymethylt ransferase activity in samples isolated from human brain 12 h after de ath compared with that obtained from the same human brain tissue maint ained at room temperature for up to 24 h after death. These results su ggest that the level of carboxymethylation of proteins from human post -mortem brain obtained within 24 h of death is not significantly diffe rent to the level present at the time of death. To characterize the di stribution of protein carboxymethylation in human brain, nine regions of post-mortem brain were sampled from 16 human subjects. Protein carb oxymethyltransferase activity was lowest in the cerebellum (P < 0.05) and highest in cortical white matter compared with other regions of th e brain (P < 0.05), No significant differences in protein carboxymethy ltransferase activity were noted between other regions of the cortex o r the subcortical regions. 4. In human cortical white matter there are more available sites for protein carboxymethylation than other brain regions. This may explain the greater sensitivity of white matter to t he adverse consequences of hypomethylation associated with vitamin B(1 2 )deficiency. Post-mortem brain tissue can serve as a tool for the st udy of physiological or pathological factors which influence human bra in protein methylation in vivo.