Glutamine enzymes acting

Glutamine and ATP analogues were useful to probe the reaction mechanism, but these inhibitors are likely to interfere with many other enzymes acting on the same substrates. More recently, analogues of puromycin (22) (Table 5) were synthesized and evaluated as mechanism-based selective inhibitors of H. pylori... 

Ammonia is produced by deamination of glutamine, glutamate, other amino acids, and adenylate. A considerable quantity is derived from intestinal bacterial enzymes acting on urea and other nitrogenous eompounds. The urea comes from body fluids that diffuse into the intestine, and the other nitrogenous products are derived from intestinal metabolism (e.g., glutamine) and ingested protein. The ammonia diffuses across the intestinal mucosa to the portal blood and is eonverted to urea in the liver. 

Three major feedback mechanisms cooperate in regulating the overall rate of de novo purine nucleotide synthesis and the relative rates of formation of the two end products, adenylate and guanylate (Fig. 22-35). The first mechanism is exerted on the first reaction that is unique to purine synthesis—transfer of an amino group to PRPP to form 5-phosphoribosylamine. This reaction is catalyzed by the allosteric enzyme glutamine-PRPP amidotransferase, which is inhibited by the end products IMP, AMP, and GMP. AMP and GMP act synergisti-cally in this concerted inhibition. Thus, whenever either AMP or GMP accumulates to excess, the first step in its biosynthesis from PRPP is partially inhibited. 

In intestinal epithelial cells the same apoB gene that is used to synthesize apoB-100 in the liver is used to make the shorter apoB-48 (48%) protein. This is accomplished in an unusual way that involves "editing" of the mRNA that is formed. Codon 2153 in the mRNA for the protein is CAA, encoding glutamine. However, the cytosine of the triplet is acted on by a deaminase, an editing enzyme, to form UAA, a chain termination codon.14 15 A third form of apoB is found... 

Let us first consider the situation under conditions of nitrogen excess (see fig. 21.5). The first regulatory protein in the cascade is converted into a uridylyl-removing enzyme. This enzyme hydrolyzes UMP from a PII 3 UMP protein that acts in concert with adenylyltransferase to form adenylate glutamine synthase. The resulting adenylylated enzyme is inactive. 

Fe/S clusters in regulatory enzymes have been proposed to act as sensors in such a manner that, upon detection of a measurand, the cluster disintegrates and activity stops. Putative examples are NO sensing by the [2Fe-2S] cluster in the terminal enzyme of heme synthesis, ferrochelatase [8], and 02 sensing by the [4Fe-4S] cluster in the regulatory enzyme of purine nucleotide biosynthesis, glutamine 5-phosphoribosyl-l-pyrophosphate amidotransferase [9], This is of course not a catalytic activity, since the cluster is destroyed in the action. 

---