Disease relevance of ADA

• ADA activity is known to decrease markedly in chick embryo fibroblasts (CEF) transformed by Rous sarcoma virus [1].
• 5'-Iodotubercidin (100 nM) completely protected neurons against toxicity of adenosine plus adenosine deaminase inhibitors [2].
• 3. Adenosine deaminase (2.5 i.u./ml) increased the size of the EPSP by 70%, suggesting that endogenous adenosine modulates synaptic transmission in the ciliary ganglion [3].

High impact information on ADA

• The high affinity between the catalytic small subunit ADA (SS-ADA) and its membranal complexing protein (ADCP) (which abounds on the plasma membrane of CEF) allowed the hybridization of fluorescent labeled SS-ADA with native ADCP on CEF [1].
• The transformation process is shown to have led to increased membrane fluidity and rotational mobility of ADCP as well as to its reduced availability to SS-ADA binding [1].
• 8. We conclude that adenosine deaminase and adenosine kinase play an important role in the metabolism of intracellular concentrations of adenosine and thereby regulate the growth and development of sympathetic neurons [2].
• 4. Inhibitors of adenosine deaminase dramatically facilitated the toxic action so that physiologically relevant concentrations of adenosine were neurotoxic [2].
• RESULTS: Removal of adenosine from the culture medium with adenosine deaminase resulted in an enhanced ability of the adenosine A1 receptor agonist R-N6-(2-phenylisopropyl)-adenosine to exert a direct, negative inotropic effect and to inhibit isoprenaline stimulated adenylyl cyclase activity [4].

Biological context of ADA

• 2. The deoxyadenosine/adenosine deamination ratios ranged from 0.75 to 0.84 for both ADA activities [5].
• Chicken embryo fibroblasts exposed to weak, time-varying magnetic fields share cell proliferation, adenosine deaminase activity, and membrane characteristics of transformed cells [6].
• Adenosine deaminase 2 from chicken liver: purification, characterization, and N-terminal amino acid sequence [7].

Anatomical context of ADA

• 5. The temperature optima for erythrocyte and heart ADA were 30 and 35 degrees C, respectively [5].
• Adenosine deaminase (ADA) is involved in purine metabolism and plays an important role in the mechanism of the immune system [7].
• 1. The adenosine deaminase (ADA) activities of chicken erythrocyte and heart cytosols had pH optima of 6 [5].
• Binding of the antagonist radioligand [3H]-8-cyclopentyl-1,3-dipropylxanthine in membranes from myocytes pre-exposed to adenosine deaminase showed a 70% increase in the adenosine A1 receptor density and a 54% increase in the proportion of the high affinity adenosine A1 receptor: control 33(5)%, n = 5, versus sensitised 49(3)%, n = 5, p < 0.01 [4].
• Chicken egg yolk contains an adenosine deaminase that was investigated after purifying about 500 times [8].

Associations of ADA with chemical compounds

• Pyrene-labeled, small subunit ADA was applied to cultured (normal) CEF, which have available and abundant ADA complexing protein (ADCP) on their plasma membranes [6].
• 3. For erythrocyte ADA, Km values were 8.9-12.9 microM adenosine (range) and 8.3 microM 2'-deoxyadenosine [5].
• For heart ADA, Km values were 6.7-12.0 microM adenosine (range) and 5.3 microM 2'-deoxyadenosine [5].
• 4. Inosine was a competitive inhibitor of both erythrocyte (Ki = 73 microM) and heart (Ki = 109 microM) ADA [5].
• Inhibition of adenosine deaminase by 1 microM-coformycin had no effect on the formation of labelled uric acid, indicating that the initial degradation of AMP proceeds by way of deamination rather than dephosphorylation [9].

Analytical, diagnostic and therapeutic context of ADA

• Chicken embryo fibroblasts (CEF) exposed to a sinusoidally varying magnetic field (SVMF) (100 Hz, 700 microT, for 24 h) showed a remarkable rise of segmental rotational relaxation rate of adenosine deaminase (ADA, EC 3.5.4.4) as determined by multifrequency phase fluorometry [6].
• Blood cell lysates of chickens and turkeys were subjected to starch gel electrophoresis and the gels were stained for adenosine deaminase [10].

References