An enzyme in lymphocytes and myeloid cells that recycles toxic purine pathway metabolites, which are essential for metabolism of DNA and for cell viability.
ADA levels are increased in inflammatory effusions as those from the pleural, pericardium, and joints, caused by bacterial infections, granulomatous inflammation such as tuberculosis, or sarcoidosis, malignancy, and autoimmune diseases.
ADA levels are elevated neutrophil predominate effusion is well and is not a useful assay in the setting of a neutrophil-predominate effusion.
In lymphocyte-predominately effusions levels are higher in patients with tuberculosis than in those caused by other conditions.
In lymphocyte-predominate effusion a ADA level greater than 40 units per liter has significant sensitivity and specificity for a diagnosis of tuberculosis.
Adenosine deaminase
Adenosine deaminase is an enzyme involved in purine metabolism.
It is needed for the breakdown of adenosine from food and for the turnover of nucleic acids in tissues.
Chromosome 20 is its location.
One of the key enzymes of purine metabolism, associated with a high degree of amino acid sequence conservation suggesting its crucial nature of ADA in the purine salvage pathway.
It irreversibly deaminates adenosine, converting it to the related nucleoside inosine by the substitution of the amino group for a keto group.
Inosine can have its ribose removed by another enzyme called purine nucleoside phosphorylase, converting it to hypoxanthine.
Its primary function is the development and maintenance of the immune system.
Zinc is the only cofactor necessary for activity.
It is involved in the development and maintenance of the immune system, epithelial cell differentiation, neurotransmission, and gestation maintenance.
Adenosine deaminase deficiency leads to pulmonary fibrosis.
Deficiency of adenosine delaminates is one cause of severe combined immunodeficiency (SCID), particularly of autosomal recessive inheritance.
Deficient levels of ADA have also associated with pulmonary inflammation, thymic cell death, and defective T-cell receptor signaling.
With mutations causing this enzyme to be overexpressed, it may cause hemolytic anemia.
A different allele (ADA2) may lead to autism, and elevated levels of ADA has also been associated with AIDS.
There are 2 isoforms of ADA: ADA1 and ADA2.
ADA1 is found in most body cells, particularly lymphocytes and macrophages.
ADA1 is present not only in the cytosol and nucleus but also on the cell membrane attached to dipeptidyl peptidase-4, CD26.
ADA1 is involved mostly in intracellular activity
ADA1 and exists both in monomer and dimer forms.
ADA2 is in spleen,and in macrophages, where it co-exists with ADA1.
ADA2 is found predominantly in the human plasma and serum.
The two isoforms regulate the ratio of adenosine to deoxyadenosine potentiating the killing of parasites.
ADA2 is the predominant form present in blood and is increased in many diseases, particularly those associated with the immune system:
AD2 levels are elevated in rheumatoid arthritis, psoriasis, and sarcoidosis, and most cancers.
Total plasma ADA can be measured using high performance liquid chromatography or enzymatic or colorimetric techniques, and by measuring the ammonia released from adenosine when broken down to inosine.
Low ADA levels excludes tuberculosis from consideration in lymphocytic pleural effusions or peritoneal ascites.
Tuberculosis pleural effusions can now be diagnosed accurately by increased levels of pleural fluid adenosine deaminase, above 40 U per liter.
Cladribine and Pentostatin used in the treatment of hairy cell leukemia; their mechanism of action is inhibition of adenosine deaminase.