Adenosine deaminase (ADA) isoenzymes ADA1 and ADA2: diagnostic and biological role

Abstract

The isoenzymes ADA1 and ADA2 of the enzyme adenosine deaminase (ADA 3.5.4.4) deaminate mainly two nucleosides: adenosine and 2'deoxyadenosine, producing inosine and 2'deoxyinosine. Adenosine and 2'deoxyadenosine are molecules with many effects on human cells [1][2][3][4]. Thus, the homeostasis of these substances and the activity of the isoenzymes ADA1 and ADA2 in human cells are of extreme importance. Isoenzyme ADA1In humans, the isoenzyme ADA1 is ubiquitous and guarantees the downregulation of the substrates adenosine and 2'deoxyadenosine [1]. This homeostasis is particularly important because a low level of 2'deoxyadenosine is essential for a proper function in immune cells [2][3][4][5]. The isoenzyme ADA1 is also present in red cells, which are equipped with an efficient mechanism to capture and internalize 2'deoxyadenosine. Therefore, in humans, red cells form a "dialysis" system for circulating 2'deoxyadenosine and, in this way, preserve the nucleated cells from an excessive external supply of 2'deoxyadenosine [6].The importance of ADA1 in cells is revealed by the disfunction of the immune response in subjects congenitally lacking ADA1 due to inadequate homeostasis of 2'deoxyadenosine in their immune cells [2,4,6]. There are several other important effects of the substrate adenosine which also bear witness to the importance of the presence of ADA1 in the human body [7]; these will not be discussed here.The Km of ADA1 is 5.2×10 -5 M. ADA1 has an optimal pH of 7-7.5 and a similar affinity for both adenosine and 2'deoxyadenosine (2'deoxyadenosine/adenosine deaminase ratio of 0.75) [1,8].These features make ADA1 highly efficient in deaminating the substrates (adenosine and 2'deoxyadenosine) in biological sites where the pH is optimal for this isoenzyme even though the substrate concentration is very low. Isoenzyme ADA2 (ADA1-ADA2 isoenzymatic system)The isoenzyme ADA2 is not ubiquitous, but coexists with ADA1 only in monocytes-macrophages. ADA2 and ADA1 are coded by different gene loci [1,4,9,10].The Km of ADA2 is 200×l0 -5 M; ADA2 has an optimum pH of 6.5 and a weak affinity for 2'deoxyadenosine (2'deoxyadenosine/adenosine deaminase ratio of 0.25) [1,8,9]. These features make ADA2 inefficient in deaminating 2'deoxyadenosine in biological sites where the pH is higher than the optimum for this isoenzyme and the concentration of substrates is too low.Why, therefore, should ADA2 be present in monocytesmacrophages, where conditions are not suitable for its optimum function? To answer this question, which is extremely important from a biological point of view, it is necessary to consider ADA1 and ADA2 as a system which acts to guarantee the homeostasis of adenosine and 2'deoxyadenosine in monocytes-macrophages. This homeostatic mechanism involves two substrates and two isoenzymes. Both isoenzymes have similar affinity for the substrate adenosine, whilst ADA2 has a different affinity (very weak) for the substrate 2'deoxyadenosine [1,8].Through the simulation model STELLA II (High Performance System Inc., 1993), we h...

Adenosine Deaminase in Diagnosis of Tuberculosis: A Review

“…ADA-1 is found in many tissues including red blood cells. ADA-2 is found only in macrophages and monocytes 7,8 . ADA acts in proliferation and differentiation of lymphocyte, especially T lymphocyte.…”

“…Furthermore, ADA has been proposed to be a useful surrogate marker for TB because it can be detected in body fluids such as pleural, pericardial and peritoneal fluid. The levels of ADA increase in TB because of the stimulation of T cells by mycobacterial antigens 8 .…”

Adenosine Deaminase (ADA) in Tuberculous Meningitis

“…However, high ADA levels can also be found in pleural effusions secondary to pneumonia, empyema, and neoplasms especially those of hemopoietic origin, rheumatoid arthritis, and systemic lupus erythematosus. The high ADA activities in tuberculous pleural effusions are largely due to increased ADA (Gakis, 1996;Valdes et al, 1996). It is therefore important to determine the activities of ADA isoenzymes in a variety of pleural effusions.…”

Diagnostic Utility of Adenosine Deaminase in Serum and Bronchoalveolar Lavage Fluid for Screening Lung Cancer in Western Iran

“…Finally, all activities were expressed in unit per liter (U/L). Coefficient of variation (%CV) for this method is about 3%; it has a high reproducibility and very inexpensive materials are used (9). Giusti method needs to be done at 37 °C.…”

“…ADA is widely distributed in human tissues and involved in immune system development. Two major isoforms of ADA have been isolated with different characteristics (8,9). Alteration in serum ADA activity has been reported in a broad range of lung diseases such as tuberculosis and chronic obstructive pulmonary disease (COPD) (10,11).…”