Acetyl adenylate, hydrolysis

The structurally similar amino acid-RNA derivatives also react rapidly with hydroxylamine and are energy-rich compounds, since they are in reversible equilibrium with ATP (Hoagland et al, 1958 Mager and Lipmann, 1958 Holley and Goldstein, 1959). Within the acyl phosphate series, acetyl adenylate (1737 cm ) has a free energy of hydrolysis at pH 7 which is similar to that of acetylimidazole and is... 

A variety of enzymatic mechanisms for antibiotic resistance are known. Hydrolysis of the lactam rings of /3-lactams, cephalosporins, and carbapenams destroys their ability to inhibit transpeptidases that cross-link peptidoglycan in bacterial cell walls. Modification of aminoglycoside antibiotics by acetylation, phosphorylation, or adenylation interferes with their ability to bind to the 16S subunit of the ribosome. Streptogramin activity can be destroyed by acetylation or by an elimination reaction that opens the lactone ring. The enzymes responsible for these detoxification reactions evolved in response to naturally occurring antibiotics, but are easily adapted to modify semisynthetic and completely synthetic antibiotics. For example, only a few point mutations are needed to enhance the ability of TEM /3-lactamases to hydrolyze third-generation cephalosporins such as cefotaxime and ceftazidime. ... 

Hydroxy- 9-methylglutaryl CoA further yields acetyl CoA and acetoacetic acid, as was shown earlier by Coon et cU. (I48). In biotin deficiency the carboxylation reaction does not occur. It was shown by Lynen et al. that the actual carboxylation is preceded by the enzymic dehydration (rf jS-hydroxyisovaleryl CoA to /8-methylcrotonyl CoA, which is the true substrate for the entry of CO2. TTiis occurs at the expense of the hydrolysis of the terminal P04 of ATP. The unsaturated intermediate is then saturated by the addition of H2O to yield the final product. The critical step of this carboxylation is the conversion of CO2 to a reactive form. The analogy of the biochemical activation of other substances through an acyl adenylate type of compound did not fit CO2 activation. The final mechanism of the activation of CO2 was derived from the discovery that the carboxylase enzyme was a biotin-protein. This observation explains earlier work 149) which indicated that biotin is a cofactor of the fatty acid-synthesizing enzyme system. When the purified carboxylase was incubated with P and ATP an exchange reaction of phosphate occurred, which was inhibited by avidin, a protein which specifically binds biotin. This indicated that the primary reaction in CO2 fixation is the combination of ATP with the biotin-protein enzyme to yield ADP biotin-protein -f P. The active CO2 is then the product of an exchange reaction between ADP and C02 which is finally attached to the biotin-protein complex. 

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