THE HUMAN SERUM PARAOXONASE ARYLESTERASE GENE (PON1) IS ONE MEMBER OFA MULTIGENE FAMILY

A physiological role for paraoxonase (PON1) is still uncertain, but it catalyzes the hydrolysis of toxic organophosphates. Evidence that, th e human genome contains two PON1-like genes, designated PON2 and PON3, is presented here. Human PON1 and PON2 each have nine exons, and the exon/intron junctions occur at equivalent positions. PON1 and PON2 gen es are both on chromosome 7 in human and on chromosome 6 in the mouse. Turkey and chicken, like most birds, lack paraoxonase activity and ar e very susceptible 60 organophosphates. However, they have a PON-like gene with similar to 70% identity with human PON1, PON2, and PON3, Ano ther unexpected finding is that the deduced amino acid sequences of PO N2 in human, mouse, dog, turkey, and chicken and of human PON3 are all missing the amino acid residue 105, which is lysine in human PON1. Th e expanded number of PON genes will have important implications for fu ture experiments designed to discover the individual functions, cataly tic properties, and physiological roles of the paraoxonases. (C) 1996 Academic Press, Inc.