Xanthosine monophosphate

Human type II inosine monophosphate dehydrogenase catalyses NAD-dependent conversion of inosine monophosphate (IMP) into xanthosine monophosphate (XMP) measurements of the primary kinetic isotope effect using [ H]IMP suggest that both substrates (IMP and NAD) can dissociate from the enzyme-substrate complex therefore, the kinetic mechanism is not ordered. NMR studies indicate hydride transfer to the B or pro-S face of the nicotinamide ring of NAD, while kinetic studies suggest... 

Xanthine Ribose Xanthosine Xanthosine monophosphate (XMP) xanthinylic acid Xanthosine diphosphate Xanthosine triphosphate... 

GMP is also made in the de novo biosynthetic pathway of purine nucleotide biosynthesis from xanthosine monophosphate, as shown in Figure 22.6. 

Ribarvirin is a broad-spectmm antiviral agent that inhibits viral mRNA synthesis (Section 27.10). A step in the metabolic pathway responsible for the synthesis of guanosine triphosphate (GTP) converts inosine monophosphate (IMP) into xanthosine monophosphate (XMP). Ribarvirin is a competitive inhibitor of the enzyme that catalyzes that step. Thus, ribarvirin interferes with the synthesis of GTP and, therefore, with all nucleic acid synthesis. 

GMP is also synthesized from IMP in two steps (Fig. 41.8). In the first step, the hypoxanthine base is oxidized by IMP dehydrogenase to produce the base xanthine and the nucleotide xanthosine monophosphate (XMP). Glutamine then donates the amide nitrogen to XMP to form GMP in a reaction catalyzed by GMP synthetase. This second reaction requires energy, in the form of ATP. 

GMP synthesis The two reactions of GMP synthesis are an NAD -dependent oxidation followed by an amidotransferase reaction. In Step 1, IMP dehydrogenase employs the substrates NAD and H2O in catalyzing oxidation of IMP at C-2. The products are xanthylic acid (XMP or xanthosine monophosphate), NADH, and H. GMP is a competitive inhibitor (with respect to IMP) of IMP dehydrogenase. In Step 2, transfer of the amido-N of glutamine to the C-2 position of XMP yields GMP. This ATP-dependent reaction is catalyzed by GMP synthetase. 

The conversion of the adenine ring to guanine takes place by the deamination of AMP to inosine monophosphate (IMP), followed by oxidation of IMP to xanthosine monophosphate (XMP) and amination of XMP to GMP. Bacterial mutants which lack either the dehydrogenase or the aminase cannot convert adenine to nucleic acid guanine (19,20). In general the interconversion of purines does not take place by reversible reactions operating in either direction. 

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