Purification and Characterization of a Genetically Determined Rabbit Serum Esterase.

The destruction of atropine (nn-hyoscyamine) was first reported by Fleischmann over 50 years ago (1). Subsequently, it was demonstrated that this destruction is mediated by a hydrolytic enzyme (2) which is detectable in the sera and organs of but a fraction of rabbits (3). Genetic analysis indicates that atropinesterase (EC 3.1 .l. 10) activity is inherited as an incompletely dominant Mendelian character (4). Although no morphological or physiological phenotypic effects may be attributed to the presence of this enzymatic activity, it has been shown to impart resistance in rabbits to the pharmacological effects of administered atropine (5). Although extensively studied in microbial systems, geneenzyme relationships have remained less explored in higher organisms. The present studies on rabbit serum .atropinesterase were therefore initiated with the intent of developing this system for investigation in wivo and in vitro of the gene-enzyme relationship in vertebrates. Towards this end it has been first necessary to gain insight into the nature of this enzyme. Accordingly, it has been purified and inhibitor and substrate specificities have been investigated. Evidence is presented indicating that the atropinesterase gene determines the presence of a single enzyme protein species with broad substrate specificity of the B-esterase tme (6,7).