Comparison and Possible Homology of Isozymes of Adenosine Deaminase in Aves and Humans

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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 K(m) 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 K(m), a lower pH optimum, and a greater resistance to inhibition by erythro-9-(2-hydroxy-2-nonyl) adenine (EHNA). The similarity in K(m)s 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 amounts 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.