Several of the adenosine deaminase isozymes are glycoproteins

Abstract

THE basis for the complex multiple molecular forms (isozymes) of the enzyme adenosine deaminase (ADA) has been widely studied. The ADA found in human erythrocytes (so-called ‘red cell’ ADA) exhibits genetically determined polymorphism detectable by electrophoresis¹, has reactive thiol groups² and has a low molecular size³.‘Red cell’ ADA is present in various tissues other than the red cell³, but additional adenosine deaminases. the so-called tissue ADA isozymes a, b, c, d and e named in order of decreasing electrophoretic mobility, which exhibit rather different properties. occur in varying amounts in nonerythroid tissues. With the discovery that the deficiency of ‘red cell’ ADA in certain patients with combined immune deficiency disease is accompanied by the deficiency of all the other isozymes^4–6. it became clear that all the forms were probably coded by a single ADA locus. The ‘red cell’ ADA can be converted into the characteristic ‘tissue’ isozymes by tissue extracts both from normal individuals^7,8 and from patients with combined immune deficiency disease. A converting factor has been isolated and partially purified and is thought to be a protein⁹. This protein is presumably associated with one or several ‘red cell’ ADA molecules to form the ‘tissue’ isozymes, accounting for the alteration in properties (increase in molecular size, loss of detectable genetically determined electrophoretic variation and loss of thiol reactivity³). We present here evidence, from lectin affinity chromatography and experiments with neuraminidase. that most of the multiple forms of ‘tissue’ ADA are glycoproteins which differ in their accessible sugar residues. This suggests that the converting factor may be a single glycoprotein with heterogenous carbohydrate content.