Substrate channeling is the passing of the intermediary metabolic product of one

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...

directly to another enzyme or

active site In biology and biochemistry, the active site is the region of an enzyme where substrate molecules bind and undergo a chemical reaction. The active site consists of amino acid residues that form temporary bonds with the substrate (binding site) a ...

without its release into solution. When several consecutive enzymes of a metabolic pathway channel substrates between themselves, this is called a

metabolon In biochemistry, a metabolon is a temporary structural-functional complex formed between sequential enzymes of a metabolic pathway, held together both by non-covalent interactions and by structural elements of the cell, such as integral membrane pro ...

. Channeling can make a

metabolic pathway In biochemistry, a metabolic pathway is a linked series of chemical reactions occurring within a cell. The reactants, products, and intermediates of an enzymatic reaction are known as metabolites, which are modified by a sequence of chemical reac ...

more rapid and efficient than it would be if the enzymes were randomly distributed in the

cytosol The cytosol, also known as cytoplasmic matrix or groundplasm, is one of the liquids found inside cells (intracellular fluid (ICF)). It is separated into compartments by membranes. For example, the mitochondrial matrix separates the mitochondri ...

, or prevent the release of unstable intermediates. 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 Pyruvate dehydrogenase complex (PDC) is a complex of three enzymes that converts pyruvate into acetyl-CoA by a process called pyruvate decarboxylation. Acetyl-CoA may then be used in the citric acid cycle to carry out cellular respiration, and t ...

, is by a substrate being attached to a flexible arm that moves between several active sites (not very likely). Another possibility is by two active sites being connected by a tunnel through the protein and the substrate moving through the tunnel; this is seen in

tryptophan synthase Tryptophan synthase or tryptophan synthetase is an enzyme () that catalyses the final two steps in the biosynthesis of tryptophan. It is commonly found in Eubacteria, Archaebacteria, Protista, Fungi, and Plantae. However, it is absent from Animali ...

. A third possibility is by a charged region on the surface of the enzyme acting 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 Dihydrofolate reductase, or DHFR, is an enzyme that reduces dihydrofolic acid to tetrahydrofolic acid, using NADPH as an electron donor, which can be converted to the kinds of tetrahydrofolate cofactors used in 1-carbon transfer chemistry. In ...

thymidylate synthase Thymidylate synthase (TS) () is an enzyme that catalyzes the conversion of deoxyuridine monophosphate (dUMP) to deoxythymidine monophosphate (dTMP). Thymidine is one of the nucleotides in DNA. With inhibition of TS, an imbalance of deoxynucleo ...

. The channeling of aminoacyl-tRNA for protein synthesis in vivo has been also reported. A presence of channel in enzyme structure is rather common feature as more than 68% of enzymes have active site access channels. Enzyme channels can be identified and characterized b
MOLEonline
software.

References

Enzyme kinetics {{enzyme-stub

See also

References