What diseases are 2'-Deoxyadenosine levels associated with?

2'-Deoxyadenosine is a derivative of the adenosine nucleoside with adenine (A) as the nucleobase, which pairs with deoxythymidine (T) in double-stranded DNA. Deoxyadenosine is an essential component of DNA. When deoxyadenosine levels are high enough, it can act as an immunotoxin and a metabolic toxin. Immunotoxins damage, limit the function of, or destroy immune cells. Metabolic toxins are endogenous metabolites. Chronically high levels of deoxyadenosine are associated with adenosine deaminase (ADA) deficiency, an inborn error of metabolism. ADA deficiency impairs the immune system and causes severe combined immunodeficiency (SCID). People with SCID lack nearly all immune protection against bacteria, viruses, and fungi. They are prone to recurrent and persistent infections that can be very severe or even life-threatening. These infections are often caused by "opportunistic" organisms that do not normally cause disease in people with a normal immune system.

The main symptoms of ADA deficiency are pneumonia, chronic diarrhea, and widespread rash. The mechanism by which dATP functions as an immunotoxin is as follows: Since deoxyadenosine is a precursor to dATP, the accumulation of dATP in cells inhibits ribonucleotide reductase and prevents DNA synthesis, so the cells cannot divide. Since developing T and B cells are some of the most active mitotic cells, they are unable to divide and multiply in response to immune challenges. High levels of deoxyadenosine also lead to an increase in S-adenosylhomocysteine, which is toxic to immature lymphocytes.

In addition, studies have shown that deoxyadenosine, a substance with a much weaker effect on epidermal adenylate cyclase stimulation, has been shown to be as effective as adenosine in inhibiting keratinocyte proliferation. Both adenosine and deoxyadenosine have a significant inhibitory effect on keratinocyte growth, [3H]thymidine uptake, and keratinocyte mitosis. Deoxyadenosine has a greater effect on keratinocyte growth and [3H]thymidine uptake than adenosine.

You may like