Channeling of substrates and intermediates in enzyme-catalyzed reactions

The three-dimensional structures of tryptophan synthase, carbamoyl phosphat e synthetase, glutamine phosphoribosylpyrophosphate amidotransferase, and a sparagine synthetase have revealed the relative locations of multiple activ e sites within these proteins. In all of these polyfunctional enzymes, a pr oduct formed from the catalytic reaction at one active site is a substrate for an enzymatic reaction at a distal active site. Reaction intermediates a re translocated from one active site to the next through the participation of an intermolecular tunnel. The tunnel in tryptophan synthase is similar t o 25 Angstrom in length, whereas the tunnel in carbamoyl phosphate syntheta se is nearly 100 Angstrom, long. Kinetic studies have demonstrated that the individual reactions are coordinated through allosteric coupling of one ac tive site with another. The participation of these molecular tunnels is tho ught to protect reactive intermediates from coming in contact with the exte rnal medium.