Effect of <img src='/image/spc_char/beta.gif' border=0>-lactamase-catalyzed hydrolysis of cephalosporins on peroxynitrite-mediated nitration of serum albumin and cytochrome c

Abstract

The hydrolysis of <img src='/image/spc_char/beta.gif' border=0>-lactam antibiotics by <img src='/image/spc_char/beta.gif' border=0>-lactamases is one of the major bacterial defense systems. These enzymes generally hydrolyze a variety of antibiotics including the latest generation of cephalosporins, cephamycins and imipenem. In this paper, the effect of cephalosporins-based antibiotics on the peroxynitrite-mediated nitration of protein tyrosine is described. Although some of the antibiotics have weak inhibitory effect on the nitration reactions in the absence of <img src='/image/spc_char/beta.gif' border=0>-lactamase, they exhibit very strong inhibition in the presence of <img src='/image/spc_char/beta.gif' border=0>-lactamase. This is due to the elimination of heterocyclic thiol/thione moieties from cephalosporins by <img src='/image/spc_char/beta.gif' border=0>-lactamase-mediated hydrolysis. After the elimination, the thiols/thiones effectively scavenge peroxynitrite, leading to the inhibition of the nitration reactions.