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.

Key Words:

• 1-tyrosine hydroxylase
• Dopamine B-hydroxylase
• Phenylethanolamine N-methyltransferase
• Recombinant DNA
• Similar Gene Coding Sequences