Question

Describe the characteristic chemical step that occurs during covalent catalysis. Which four different types of catalytic mechanisms did we discuss to hydrolyze peptide bonds in proteins?

Answer 1

In an enzymatic reaction, covalent catalysis occurs when the substrate become temporarily covalently attached to the enzyme during the catalytic reaction. In this reaction, the enzyme contains a reactive group, usually a nucleophilic residue or an electrophilic residue, which reacts with the substrate through a nucleophilic or electrophilic attack. The nucleophilic groups can be either RCOO-, RNH, ROH that are present on the side-chains of amino acid residues, or the nitrogen atoms of the imidazole ring of histidine residues. The electrophilic moieties of substrates may be acyl, phosphoryl, or glycosyl groups, so the covalent intermediates would be acyl-, phosphoryl-, and glycosyl-enzyme complexes. Enzyme molecules are poor in electrophilic groups, but electrophilic catalysis does occur with those enzymes that contain metals or prosthetic groups that act as electron sinks during catalysis. The charge loss in the reaction during transitional state will then accelerate the hydrolysis.

Rather than lowering the activation energy for a reaction pathway, covalent catalysis provides an alternative pathway for the reaction (via to the covalent intermediate) and so is distinct from true catalysis. A true proposal of a covalent catalysis would require, for example, a partial covalent bond to the transition state by an enzyme group, and such effects do not contribute significantly to catalysis.