Metabolite 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, or prevent the release of unstable intermediates.
It can also protect an intermediate from being consumed by competing reactions catalyzed by other enzymes.
Mechanisms for channeling
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.
Controversies
Channeling of NADH between oxidoreductases
Some authors have maintained that direct transfer of NADH from one enzyme as product to another as substrate is a common phenomenon. However others, such as Gutfreund and Chock and Pettersson Pettersson is a common Swedish patronymic surname, meaning "son of Peter".
Geographical distribution
As of 2014, 92.7% of all known bearers of the surname ''Pettersson'' were residents of Sweden (frequency 1:151), 1.7% of Finland (1:4,550), 1.3% o ...
have argued that the experimental evidence is too weak to support such a conclusion. In a more recent study Svedružić and colleagues conclude that such direct transfer is a real phenomenon, but they sound a note of caution:Our results also show that it is impossible to design experiments that can conclusively analyze substrate channeling in cells if we do not understand the underlying molecular principles and the properties of the related enzymes.
Physiological effects of metabolite channeling
It is sometimes suggested, for example by Ovádi, that metabolite channeling decreases the concentration of metabolite in free solution. However, it has also been argued that there is no net effect on the free concentration in steady-state conditions, a claim disputed by others. More recent authors consider this and other questions about channeling to be unresolved: "Substrate channeling ''in vivo'' has also been a subject of yet to be resolved debates," or they recognize that an effect on free concentration exists, but is "generally small."
See also
* Enzyme kinetics
* Enzyme assay
* Enzyme catalysis
Enzyme catalysis is the increase in the rate of a process by a biological molecule, an "enzyme". Most enzymes are proteins, and most such processes are chemical reactions. Within the enzyme, generally catalysis occurs at a localized site, calle ...
References
Enzyme kinetics
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