Hydrolytic deamination

Two amino acids—asparagine and glutamine—contain acid-amide groups in the side chains, from which NH3 can be released by hydrolysis (hydrolytic deamination). In the blood, glutamine is the most important transport molecule for amino nitrogen. Hydrolytic deamination of glutamine in the liver also supplies the urea cycle with NH3. 

This enzyme [EC 3.5.3.13] catalyzes the hydrolytic deamination of iV-formimino-L-glutamate to yield iV-formyl-L-glutamate and ammonia. 

Adenosine deaminase catalyzes the hydrolytic deamination of adenosine and 2 -deoxyadenosine to inosine and 2 -deoxyinosine respectively. Inhibition of adenosine deaminase leads to an accumulation of its substrates which results in adenosine receptor-mediated effects. Most inhibitors are not reported to have antinociceptive properties, but 2 -deoxycoformycin was proven to have an inhibitory effect on pain transmission (Poon and Sawynok, 1999), and Fujisawa Pharmaceuticals claim adenosine deaminase inhibitors to be active against chronic pain. 

Phosphorylation of dCDP to dCTP (step k, Fig. 25-14) completes the biosynthesis of the first of the pyrimidine precursors of DNA. The uridine nucleotides arise in two ways. Reduction of UDP yields dUDP (step), Fig. 25-14). However, the deoxycytidine nucleotides are more often hydrolytically deaminated (reactions / and / ) 274 Methylation of dUMP to form thymidylate, dTMP (step n, Fig. 25-14), is catalyzed by thymidylate synthase. The reaction involves transfer of a 1-carbon unit from methylene tetrahydrofolic acid with subsequent reduction using THF as the electron donor. A probable mechanism is shown in Fig. 15-21. See also Box 15-E. Some bacterial transfer RNAs contain 4-thiouridine (Fig. 5-33). The sulfur atom is introduced by a sulfurtransferase (the Thil gene product in E. coli). The same protein is essential for thiamin biosynthesis (Fig. 25-21)274a... 

Both the fungus Eremothecium (Box 15-B) and mutants of Saccharomyces have been used to deduce the pathways of riboflavin synthesis outlined in Figure 25-20. The first reaction (step a) is identical to step a of Fig. 25-19 but is catalyzed by a different GTP cyclohydrolase.362 Instead of an Amadori rearrangement it catalyzes the hydrolytic deamination and dephosphorylation (step b) to give the flavin precursor... 

The hydrolytic deamination catalyzed by rabbit and rat muscle AMP aminohydrolase may be facilitated by Zn2+ (133, 154a) in contrast to the mediation of a common purinyl enzyme intermediate for adenosine aminohydrolase catalysis (see Section III). 

Carbon-14 and nitrogen-15 heavy-atom KIEs in the hydrolytic deamination of adenosine 5-monophoshate (AMP 513) with AMP deaminase... 

S. Sun et al., Radical-mediated cytosine and S-methylcytosine hydrolytic deamination reactions. Int. J. Quantum Chem. 106, 1878-1894 (2006)... 

Because of its reactivity, water destroys hydrolytically unstable organic species. Thus, a hypothetical form of life in a Titan hydrocarbon ocean would be less subject to the hydrolytic deamination of its nucleobases, and would be able to guide reactivity more easily than life in water. 

The electrolysis products in neutral medium included one additional absorbing substance, the chromatographic properties of which, together with its reaction with the Fink reagent to give a yellow product85), pointed to its being 5,6-dihydro-cytosine 86), further confirmed by its hydrolytic deamination to a product identical with 5,6-dihydrouracil. 

Guanase catalyzes the hydrolytic deamination of guanine to xanthine and ammonia. Its activity in serum is strongly elevated in patients with liver disease. 

ADA and AMPDA are enzymes involved in the purine cycle and they catalyze the hydrolytic deamination of purine nucleosides and nucleotides. In the last few years these biocatalysts have shown a great utility in biocatalysis, because they display broad substrate specificity and their use can also be extended to carbocyclo-nucleosides and acyclonucleosides [34], The general process that takes place using these enzymes is outlined in Scheme 10.15. 

Scheme 10.15 Hydrolytic deamination of ADA and AMPDA of adenosine and adenylic acid.

R Diolkylphenal, axodiazine. SOsNa Fig. 90. Hydrolytic deamination reactions. 

Other biological molecules are labile under UV-B irradiance and DNA is among the most affected. DNA is constantly subject to hydrolytic deamination, methylation and insertion by organic electrophyles and other compounds. In addition to this, UV-B radiation causes severe alterations... 

Scheme 4.27 Hydrolytic deamination of nucleoside analogs (top) can be blocked by fluorination in the 2 -position, destabilizing the carbocationic reaction intermediate (box). The half-life of dideoxyadenosine (X = H) at pH 1 is 35 s whereas the 2 -fluoro analog (X = F, active as a reverse transcriptase inhibitor) is completely stable for 20 days [59]. The antiherpetic Gemcitabine (bottom) is stabilized by the same principle.

Alkahne, hydrolytic deamination of cytidyhc acid h (under conditions which avoided phosphate migration) yielded midyhc acid h, proving that... 

Figure 11.1 Representative BER and NER substrates, (a) Bases modified by hydrolytic deamination (U, Hyp), oxidation (8-oxo-G, TG), alkylation (3-meA, eA), and hydrolysis (AP site) are processed by BER. The atoms of the molecule that differ from native DNA are...

Treatment of 1-ethyladenine 192 with 0.2 N aqueous NaOH caused rearrangement to iV-ethyladenine 194 with two by-products, hypoxanthine 196 and 1-ethylhypoxanthine 198, resulting from unusual hydrolytic deaminations of the intermediate 193 via 195 and 197, respectively. Rates increased with an increase in the pH of the medium. Similar results were also reported for the rearrangement of 7-alkyl-1 -methyladenines (94CPB382) (Scheme 63). 

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