Guanosine deamination

Purine (left). The purine nucleotide guano-sine monophosphate (CMP, 1) is degraded in two steps—first to the guanosine and then to guanine (Gua). Guanine is converted by deamination into another purine base, xanthine. 

An important reaction is the deamination of amines by dilute nitrous acid. This reagent, by a complex mechanism, converts the amino groups of cytidine, adenosine, and guanosine to hydroxyl groups hydroxy compounds tautomerize to the corresponding amides (Eq. 5-14). 

Transfer RNA molecules are notable for containing unusual nucleotides (Fig. 5) such as 1-methylguanosine (m G), pseudouridine OF), dihydrouridine (D), inosine (I) and 4-thiouridine (S4U). These are created by modification of guano-sine and uridine after tRNA synthesis. For example, inosine is generated by deamination of guanosine. 

The next reaction is the deamination of guanosine to xanthine. Xanthine needs only one more oxygen to form uric acid. 

Deamination with adenosine deaminase is widely used for the synthesis of guanosine derivatives, e.g. formation of... 

The deamination or action of nitric oxide on guanosine gives xanthine (X) (91), which is a mutagenic lesion. dX had been assumed to be an unstable lesion, but has been shown to be relatively stable when present in a duplex at pH 7, though depurination occurs at pH < 4. In a template, HIV-RT incorporated dCTP and dTTP opposite dX with equal efficiency, whilst Kle-now fragment (exo-) preferentially incorporated dCTP. 7-Deaza-dX has also been prepared and incorporated into ODNs. ... 

Stereochemical Configuration. Deamination by means of nitrous acid transforms adenosine into inosine (ribosyl-hypoxanthine), and guanosine into xanthosine (ribosyl-xanthine). These four purine nucleosides are hydrolyzed rapidly, and with equal ease, by dilute mineral acids. They are also all hydrolyzed by the same enzyme, so it is reasonable to presume that they are similarly constituted as regards the stereochemical disposition at the sugar-base link. Whether this is of the a- or i8-configuration is still unknown. 

In an attempt to shed some light on the mutagenic effects of nitrous acid on nucleic acids, Shapiro re-investigated the deamination of adenosine, cytidine, and guanosine with nitrous acid. Whereas adenosine and cytidine gave the expected products (namely, inosine and uridine, respectively), guanosine afforded, in addition to xanthosine, a small proportion of 2-nitroinosine (227), which was isolated as the ammonium salt. 

Guanosine monophosphate can be converted to IMP by a reductive deamination and the resulting IMP can produce AMP. The salvage pathway is of great importance to extrahepatic cells, which cannot either make purines de novo or synthesize purines in sufficient quantities. The salvage pathway also allows for the use of purine derivatives such as 6-mercaptopurine and 6-thioguanine as antimetabolites in chemotherapy. 

The HGXPRTase activity appears to be the major route of purine salvage. Adenine is salvaged by deamination to hypoxanthine whereas adenosine can be either phos-phorylated directly or deaminated. Guanosine is directly phosphorylated to GMP or cleaved to guanine. 

Adenosine and AMP can be deaminated by adenosine deaminase and AMP deaminase, respectively, to form inosine and IMP (see Fig. 41.10). Adenosine is also the only nucleoside to be directly phosphorylated to a nucleotide by adenosine kinase. Guanosine and inosine must be converted to free bases by purine nucleoside phosphorylase before they can be converted to nucleotides by HGPRT. 

Selective quenching allows also to put into evidence and to study a conformational change within a protein. ADAR2 (adenosine deaminase that acts on RNA) is a -80-kDa protein that efficiently deaminates the R/G site of GluR-B pre-mRNA sequences in vitro (O Connell et al. 1997). This enzyme has an RNA binding domain (RBD)l located in the C-terniinal catalytic domain. Deamination of adenosine (A) in the mRNA results in inosine (I) at that position. Because inosine is translated as guanosine (G), the editing reaction causes a functional A to G replacement. 

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