Genetic information, whether inside or outside the nucleus, is exposed to a variety of harmful physico-chemical factors. Although DNA damage repair systems have been extensively studied, little information about post-repair and non-genomic DNA damage metabolism is available in the literature. Adenosine deaminase (ADA)
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Genetic information, whether inside or outside the nucleus, is exposed to a variety of harmful physico-chemical factors. Although DNA damage repair systems have been extensively studied, little information about post-repair and non-genomic DNA damage metabolism is available in the literature. Adenosine deaminase (ADA) is an abundant enzyme found on both sides of the cell membrane that regulates the concentration of adenine derivatives. In this article, it has been shown that 7,8-dihydro-8-oxo-2′-deoxyadenosine (
OXOdAdo) and (5′
R/
S) 5′,8-cyclo-2′-deoxyadenosine ((5′
R/
S)cdAdo) are suitable substrates for ADA. For this purpose, theoretical Density Functional Tight Binding and RP-HPLC analyses were applied. The products of ADA activity, i.e.,
OXOdIno (7,8-dihydro-8-oxo-2′-deoxyinosine) and (5′
R/
S) cdIno ((5′
R/
S) 8-cyclo-2′-deoxyinosine), were identified and confirmed by high-resolution mass spectroscopy. Although the (5′
R) and (5′
S)cdAdo enzymatic deamination processes are much slower (34% and 32% after 168 h, respectively) than the process observed for dAdo, 5′,8-cyclo-2′-deoxyinosine should be considered when monitoring cyclopurine levels in physiological fluids. The same should be considered in the case of
OXOdAdo, which is completely converted to
OXOdIno within one minute and may therefore be less visible than
OXOdGuo during mass spectroscopy analysis. Both these observations are important, given the abundance of 2′-deoxyadenosine on both sides of the cell membrane and its potential conversion into
OXOdAdo and (5′
R/
S)cdAdo. They may also explain why the observed level of
OXOdAdo is much lower than that of
OXOdGuo in cells and physiological fluids, even though their difference in ionisation potential is only 0.25 eV. Future studies are needed to further investigate the metabolism of DNA damage and to identify the enzymes involved in nucleic acid biochemistry.
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