Metabolite channeling is the passing of the intermediary metabolic product of one
enzyme
An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...
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, the ''binding s ...
without its release 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
In biochemistry, a metabolic pathway is a linked series of chemical reactions occurring within a cell (biology), cell. The reactants, products, and Metabolic intermediate, intermediates of an enzymatic reaction are known as metabolites, which are ...
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.
Mechanisms for channeling
Channeling can occur in several ways. One possibility, which occurs in the
pyruvate dehydrogenase complex, 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.
[ 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 one-carbon transfer chemistry. ...
-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 deoxynucleot ...
. 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 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 kinetics is the study of the rates of enzyme catalysis, enzyme-catalysed chemical reactions. In enzyme kinetics, the reaction rate is measured and the effects of varying the conditions of the reaction are investigated. Studying an enzyme' ...
* Enzyme assay
Enzyme assays are laboratory methods for measuring enzymatic activity. They are vital for the study of enzyme kinetics and enzyme inhibition.
Enzyme units
The quantity or concentration of an enzyme can be expressed in molar amounts, as with a ...
* Enzyme catalysis
Enzyme catalysis is the increase in the rate of a process by an "enzyme", a biological molecule. 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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