Regulation of phenylethanolamine N-methyltransferase

Abstract

Publisher Summary This chapter discusses regulation of phenylethanolamine N -methyltransferase (PNMT). PNMT is localized almost exclusively to the adrenal medulla, although traces of activity have been reported in heart, brain, in extra-adrenal chromaffin tissue and in sympathetic ganglia. PNMT catalyzes the N -methylation of a number of primary and secondary β-hydroxyphenylethylamine derivatives. The requirement of the enzyme for β-hydroxylated phenylethylamine substrates appears to vary with species: PNMT from monkey, rabbit, rat and human with N -methylate only phenylethylamine substrates bearing a β-hydroxyl group. PNMTs from the rat and the frog share common substrate specificities, but virtually every other biochemical parameter of these enzymes differs. These include pH and thermal optima, thermal stability and starch-block migration. When these studies are compared with those of previous findings a striking uniformity of substrate specificity is observed, coupled with an equally striking heterogeneity of electrophoretic migration. These findings suggest that the evolution of PNMT has permitted amino acid substitutions which affect charge, molecular weight and stability of the enzyme, but has not tolerated alterations at the catalytic site of the molecule, which has remained relatively constant.