Biochemistry and molecular biology of catecholamine neurons: a single gene or gene family hypothesis

Abstract

We postulate that the catecholamine synthesizing enzyme, tyrosine hydroxylase (TH), dopamine B-hydroxylase (DBH) and phenylethanolamine N-methyltransferase (PNMT) are coded for by similar gene coding sequence(s). This is based on the following observations: (1) proteolytic digestion of these enzymes produces similar peptides whose amino acid composition is nearly identical; (2) antibodies to each enzyme coprecipitate more than one of these enzymes from in vitro poly(A)mRNA translation products; (3) using hybrid selection analysis to positively identify the cDNA clones, we discovered that DBH cDNA clones cross-hybridize with PNMT mRNA, and PNMT cDNA cross-hybridize with DBH mRNA; (4) DNA hybridization analysis demonstrated that DBH and PNMT cDNA probes hybridized to several common restriction fragments of total cellular DNA. The evidence suggests that these enzymes are coded for by a single gene or linked genes coding for all catecholamine enzymes.