Substrate channeling

Substrate channeling is when the intermediary metabolic product of one enzyme is passed directly to another enzyme or active site without being released into solution. When several consecutive enzymes of a metabolic pathway channel substrates between themselves, this is called a metabolon. Channeling can make a metabolic pathway more rapid and efficient than it would be if the enzymes were randomly distributed in the cytosol, or prevent the release of unstable intermediates.[1] It can also protect an intermediate from being consumed by competing reactions catalyzed by other enzymes.

Channeling can occur in several ways. One possibility, which occurs in the pyruvate dehydrogenase complex, is when a substrate is attached to a flexible arm that moves between several active sites.[2] Another possibility is when two active sites being connected by a tunnel through the protein and the substrate moves through the tunnel, this is seen in tryptophan synthase.[1] A third possibility is when a charged region on the surface of the enzyme acts as a pathway or "electrostatic highway" to guide a substrate that has the opposite charge from one active site to another. This is seen in the bifunctional enzyme dihydrofolate reductase-thymidylate synthase.[3] The channeling of aminoacyl-tRNA for protein synthesis in vivo has been also reported.[4]

See also


  1. ^ a b Huang X, Holden HM, Raushel FM (2001). "Channeling of substrates and intermediates in enzyme-catalyzed reactions". Annu. Rev. Biochem. 70: 149–80. doi:10.1146/annurev.biochem.70.1.149. PMID 11395405. 
  2. ^ Perham RN (2000). "Swinging arms and swinging domains in multifunctional enzymes: catalytic machines for multistep reactions". Annu. Rev. Biochem. 69: 961–1004. doi:10.1146/annurev.biochem.69.1.961. PMID 10966480. 
  3. ^ Miles EW, Rhee S, Davies DR (April 1999). "The molecular basis of substrate channeling". J. Biol. Chem. 274 (18): 12193–6. doi:10.1074/jbc.274.18.12193. PMID 10212181. 
  4. ^ Negrutskii B.S., Deutscher M.P. (1991.). "Channeling of aminoacyl-tRNA for protein synthesis in vivo". Proc. Natl. Acad. Sci. USA 88 (11): 4991–5.. doi:10.1073/pnas.88.11.4991. PMC 51793. PMID 2052582.