title: Comparison and possible homology of isozymes of adenosine deaminase in Aves and humans.
abstract: Two kinetically distinct adenosine deaminase (ADA) isozymes with different molecular weights (35,000 and 100,000 daltons) are found in chicken liver in approximately equal amounts. The 100,000-dalton ADA has a markedly higher Km for adenosine and a markedly lower deaminating activity for deoxyadenosine relative to adenosine than does the 35,000-dalton ADA. A 100,000-dalton ADA isozyme has only recently been detected in mammalian tissues, where, in contrast to the chicken, it is only a trace component of total ADA activity. The human 100,000-dalton ADA isozyme, compared to the human 35,000-dalton ADA isozyme, has been reported to have a higher Km, a lower pH optimum, and a greater resistance to inhibition by erythro-9-(2-hydroxy-2-nonyl) adenine (EHNA). The similarity in KmS of the 100,000-dalton ADA isozyme in man and aves led us to hypothesize that these isozymes might be descended from a common ancestor and therefore also be similar as to other kinetic parameters. We now report that the chicken 100,000-dalton ADA, like the human 100,000-dalton isozyme, has a lower pH optimum and a greater resistance to inhibition by EHNA than does the avian or human 35,000-dalton isozyme. In addition, the avian 100,000-dalton isozyme is relatively resistant to inhibition by deoxycoformycin and has a cathodal rather than an anodal electrophoretic mobility at pH 6.5. Conversely, we report that the human 100,000-dalton ADA isozyme, similar to the avian 100,000-dalton ADA, has markedly lower relative deaminating activity for deoxyadenosine than does the 35,000-dalton ADA human isozyme. Thus, despite the marked difference in the relative amount of the 100,000- and 35,000-dalton ADA isozymes in man as compared to aves, the 100,000-dalton ADA isozymes from both species exhibit several similar kinetic properties, all of which are different from those of the 35,000-dalton ADA isozymes. We also report using a new sensitive assay, relative rates of degradation by the two chicken isozymes of several naturally occurring modified adenine nucleosides which are inhibitory to in vitro human lymphocyte proliferation.
mesh_terms: D000243:Adenosine Deaminase / Q000032:analysis / Q000378:metabolism*; D058892:Adenosine Deaminase Inhibitors; D000818:Animals; D002645:Chickens / Q000378:metabolism*; D006801:Humans; D007527:Isoenzymes / Q000032:analysis / Q000378:metabolism*; D008099:Liver / Q000201:enzymology*; D008970:Molecular Weight; D009700:Nucleoside Deaminases / Q000378:metabolism*; D013045:Species Specificity; D013154:Spleen / Q000201:enzymology*; D013379:Substrate Specificity
chemical_list: D058892:Adenosine Deaminase Inhibitors; D007527:Isoenzymes; D009700:Nucleoside Deaminases; D000243:Adenosine Deaminase