Deoxyguanosine metabolism

The structural gene for PNP in humans has been assigned to the ql3 band of chromosome 14. The enzyme is ubiquitous in human tissues with the highest specific catalytic activities in peripheral blood lymphocytes, granulocytes, erythrocytes and kidney. In most patients deficiency of enzyme activity is associated with a mutation of the structural gene for PNP. The products of adenosine deaminase - inos-ine, deoxyinosine, guanosine and 2'-deoxyguanosine (dGuo) - are all naturally occurring substrates for the enzyme. The phosphorylase generates the corresponding purine bases, hypoxanthine or guanine (see Figure 1). Of the substrates that accumulate in excess in the absence of PNP activity, only dGuo can be salvaged directly by phosphorylation to the corresponding nucleotide, 2'-deoxyguanosine monophosphate. Phosphorylation is exclusively by deoxy-cytidine kinase which results in the accumulation ultimately of deoxyGTP.

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