What is Adenosine Deaminase?

Pranav Reddy

Adenosine deaminase is a purine catabolic enzyme that is essential to purine metabolism because of its ability to remove an amine group from both adenosine and 2’-deoxyadenosine. Its importance in the body means the majority of mutations in its genetic sequence result in severe disorders. Thus, it is important to understand the mechanisms surrounding this enzyme and its role within the body.

Woman posing
Woman posing

Adenosine deaminase is a polypeptide chain approximately 363 amino acids long with a high degree of sequence conservation across many species. The enzyme contains a zinc atom at its core that directly participates in the process of removing the amine group. The zinc atom accomplishes this task by instigating the removal of a hydrogen atom from water, which forms the hydroxyl group that attacks the substrate and helps knock off the amine group. Any decrease in the stability of the zinc atom results in the elimination of adenosine deaminase enzymatic activity.

There are two isoforms of the enzyme — adenosine deaminase 1 (ADA1) and adenosine deaminase 2 (ADA2). ADA1 is more common and is found within most of the cells in the human body. It is present in both the cytosol, fluid within the cell, and attached to the outside of the cell membrane. On the other hand, ADA2 is only found within certain tissues, such as the human thymus, and blood plasma. Other minor forms of adenosine deaminase include RNA- and tRNA-specific forms, named ADAR and ADAT, respectively.

In addition to purine metabolism, this enzyme plays several additional roles within the body. The first is its role as a signaling molecule that, when released, interacts with adenosine receptors. The response to this interaction includes coronary vasodilation, reduction in heart rate and many others. Another important role is its extracellular presence where it binds to different molecules. In this role, it most likely acts as a stimulatory molecule.

The most well known disorder concerning this enzyme is adenosine deaminase deficiency, which is a dangerous disorder that affects the immune system. The cause is a mutation on the 20th chromosome, where its gene is found. This produces a nonfunctional enzyme that is incapable of breaking down deoxyadenosine. Build up of deoxyadenosine is toxic and kills T and B lymphocytes, which are vital parts of the body’s immune system. Thus, a person diagnosed with adenosine deaminase deficiency will have a malfunctioning immune system that will leave his body open to attack from bacteria and viruses.

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