Channeling of substrates and intermediates in enzyme-catalyzed reactions

Annu Rev Biochem. 2001;70:149-80. doi: 10.1146/annurev.biochem.70.1.149.


The three-dimensional structures of tryptophan synthase, carbamoyl phosphate synthetase, glutamine phosphoribosylpyrophosphate amidotransferase, and asparagine synthetase have revealed the relative locations of multiple active sites within these proteins. In all of these polyfunctional enzymes, a product formed from the catalytic reaction at one active site is a substrate for an enzymatic reaction at a distal active site. Reaction intermediates are translocated from one active site to the next through the participation of an intermolecular tunnel. The tunnel in tryptophan synthase is approximately 25 A in length, whereas the tunnel in carbamoyl phosphate synthetase is nearly 100 A long. Kinetic studies have demonstrated that the individual reactions are coordinated through allosteric coupling of one active site with another. The participation of these molecular tunnels is thought to protect reactive intermediates from coming in contact with the external medium.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • 3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)
  • Amidophosphoribosyltransferase / chemistry
  • Amidophosphoribosyltransferase / metabolism
  • Ammonia-Lyases / chemistry
  • Ammonia-Lyases / metabolism
  • Aspartate-Ammonia Ligase / chemistry
  • Aspartate-Ammonia Ligase / metabolism
  • Binding Sites
  • Carbamoyl-Phosphate Synthase (Ammonia)
  • Carbon-Nitrogen Ligases / chemistry
  • Carbon-Nitrogen Ligases / metabolism
  • Catalysis
  • Catalytic Domain
  • Enzymes / chemistry*
  • Enzymes / metabolism*
  • Ketone Oxidoreductases / chemistry
  • Ketone Oxidoreductases / metabolism
  • Multienzyme Complexes / chemistry
  • Multienzyme Complexes / metabolism
  • Tetrahydrofolate Dehydrogenase / chemistry
  • Tetrahydrofolate Dehydrogenase / metabolism
  • Tryptophan Synthase / chemistry
  • Tryptophan Synthase / metabolism


  • Enzymes
  • Multienzyme Complexes
  • 6,7-dimethyl-8-ribityllumazine synthase
  • Ketone Oxidoreductases
  • 3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)
  • Tetrahydrofolate Dehydrogenase
  • Amidophosphoribosyltransferase
  • Tryptophan Synthase
  • Ammonia-Lyases
  • formiminotetrahydrofolate cyclodeaminase
  • Carbon-Nitrogen Ligases
  • Aspartate-Ammonia Ligase
  • Carbamoyl-Phosphate Synthase (Ammonia)
  • GMP synthase (glutamine-hydrolyzing)