A DIRECT CORRELATION BETWEEN NICOTINAMIDE N-METHYLTRANSFERASE ACTIVITY AND PROTEIN-LEVELS IN HUMAN LIVER CYTOSOL

Phenotypic differences in nicotinamide N-methyltransferase (NNMT, E.C. 2.1.1.1) activity may be due to a genetic polymorphism. We report the characterisation of the hepatic NNMT activity in cytosol from normal human livers, enzyme protein levels determined by Western blotting and ELISA and mRNA levels determined by SDS-PAGE/Northern blotting. Subje cts with high NNMT activity had high levels of NNMT protein and NNMT m RNA levels in hepatic cytosol and the converse was true for individual s with low NNMT activity. No differences in sequences were seen when c DNAs of individuals with high and low NNMT activity were compared. Thu s phenotypic differences in the general population are due to differen ces in steady-state mRNA levels and not because of a polymorphism in t he coding region of the NNMT gene. (C) 1998 Elsevier Science B.V. All rights reserved.