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Adenosine deaminase (ADA) is an important enzyme in the metabolism of purine nucleosides. The human ADA gene is located at 20q13.12 and contains 12 exons. The molecular weight of the ADA protein is 110 kD. In the purine decomposition pathway, ADA catalyzes the irreversible deamination of adenosine and 2'-deoxyadenosine, produces inosine and deoxyinosine and releases NH3, which is involved in the catabolism of ATP, nucleic acids, and purines. In normal cells, the decomposition products of ATP, ADP, and AMP are mostly converted to AMP by high activity of adenosine kinase, while dATP and dAMP metabolite d adenosine are only catalyzed by deoxyadenosine kinase. The formation of d AMP, the main physiological function of ADA, is to convert d adenosine to d-inozyna.
ADA is widely distributed in various tissues of the human body, with the highest content in the thymus, spleen and other lymphoid tissues, and low contents in the liver, lung, kidney and skeletal muscle. The ADA in the blood is mainly found in red blood cells, granulocytes and lymphocytes, and its activity is about 40-70 times that of serum. ADA is more active in T lymphocytes than B lymphocytes. ADA is an indispensable enzyme in the differentiation of pre-T lymphocytes into lymphocytes, which is related to cellular cellular immune activity.
Figure 1. ADA in the purine salvage pathway. (Whitmore, et al. 2016)
ADA and Liver Disease
The ADA in serum is mainly derived from the liver, and the intrahepatic ADA mainly exists in the cytoplasm. When liver cells are damaged, ADA is released into the blood circulation, causing an increase in ADA in peripheral blood. Therefore, ADA activity is a sensitive indicator reflecting the activity of hepatocytes. It can be used as one of the routine items of liver function tests. The liver enzymes with ALT, AST, ALP and GGT can reflect the enzymological changes of liver disease.
ADA can not only reflect the degree of acute liver injury and recovery process, but also help detect residual pathological changes and progression of acute hepatitis. In chronic liver injury, serum ADA increased significantly, and its positive rate reached 85. 6% - 91. 2%. Therefore, ADA activity detection can be used as one of the screening indicators for chronic liver disease. The serum ADA activity of patients with chronic active hepatitis is significantly higher than that of chronic persistent hepatitis, so it can be used for differential diagnosis.
Serum ADA activity was significantly increased in cirrhosis, ADA activity in decompensated liver cirrhosis was higher than compensatory cirrhosis; in cirrhosis, the transaminase positive rate was lower, the increase was not obvious, and the positive rate of ADA activity was Up to 90%, the degree of increase is more obvious, therefore, ADA can be used as a good enzymology indicator for liver cirrhosis monitoring.
ADA and Tuberculosis
ADA and tuberculosisADA activity in serum, pleural effusion, cerebrospinal fluid, and bronchoalveolar lavage fluid can be elevated in tuberculous patients. Michot et al. reported that ADA has a high clinical diagnostic significance for tuberculous pleurisy, and the sensitivity of pleural effusion ADA is significantly better than finding tuberculosis, tuberculin test and tuberculosis antibody in pleural effusion, which is very high positive predictive value. ADA has high sensitivity and high specificity for the diagnosis of tuberculous pleurisy and can be used as an objective indicator of diagnosis. Koh et al. evaluated the relationship between imaging features of computed tomography (CT) tuberculosis and adenosine deaminase (ADA) values by pleural fluid analysis in patients with pleural tuberculosis. Tuberculous pleurisy patients with high ADA values were found to be more likely to develop tuberculosis. High ADA values may help predict infectious pleural substantial tuberculosis.
ADA and Diabetes
ADA is an indispensable component of T lymphocyte differentiation and maturation. ADA deficiency can cause T cell growth and development disorders and affect the body's immune function. Therefore, ADA is considered as an indicator of cellular immunity. Kurtul et al. found that serum ADA was significantly elevated in patients with DM (diabetes), especially type 2 diabetes. Studies have found that DM patients with elevated serum ADA, and diabetic nephropathy patients with elevated serum ADA activity are more obvious, and a significant positive correlation with urine microalbumin, indicating that the higher the activity of serum ADA, the greater the possibility of renal damage in DM patients.
ADA and Heart Failure
The role of adenosine as a cardioprotective agent is well known, and recent experimental studies have shown that damage to adenosine-related signal transduction contributes to the pathophysiology of chronic heart failure. He et al. conducted a case-control study of 300 Chinese Han CHF (chronic heart failure) patients and 400 healthy individuals and genotyped and correlated the 9 single nucleotide polymorphisms (SNPs) of ADA. The rs452159 polymorphism of the ADA gene was found to be significantly associated with CHF susceptibility under the dominant model. Studies by Saccucci et al. have shown a complex association between the ADA gene and coronary artery disease. In addition to controlling adenosine concentration by adenosine deamination, other functions of the ADA gene may also play a role in the susceptibility and/or clinical course of coronary artery disease.
ADA and Autoimmune Diseases
Adult-onset Still Disease (AOSD) is a systemic autoimmune disease with high heterogeneity in its etiology, clinical manifestations, and prognosis. The diagnosis of this disease is difficult, there is no specific method at present, mainly based on the exclusion method, so the rate of misdiagnosis is high. Xun et al. studied the potential role of ADA in the diagnosis of AOSD and analyzed the correlation between ADA, LDH, and WBC (white blood cell count). The results showed that serum ADA activity was higher in the ADA and AOSD groups than in the control group (systemic lupus erythematosus group and healthy control group), and there was a significant positive correlation between serum ADA and LDH, but no significant correlation with WBC. A study showing that serum ADA may play an important role in AOSD can be used as a biomarker for AOSD that is independent of whole blood WBC.