Cofactor

COFACTOR
Brief content:

Cofactors in general

Apoenzyme and holoenzyme

Coenzymes

Essential ions



Detailed content:
Cofactors in general:
What is cofactor?
The functions of cofactor
Apoenzyme and holoenzyme: some conceipts
Coenzymes
cosubstrates
prosthetic groups
Essential ions
activator ions
metalloenzyme





What is cofactor ?
The bound heme cofactor of succinate dehydrogenase, an enzyme in the mitochondrial electron transport chain
Small non-protein chemical compound that is bound ( either tightly or loosely) to an enzyme and is required by certain enzymes for catalysis.
Function:
Molecular “gofer” that carry (as shuttles) pieces of molecule from one place (the source) to another (destination).
Part of the active site → in intimate contact with the substrate( receive a piece removed from the substrate or add a piece from the substrate.
The substrate binds to the active site of the enzyme and a piece of it is cut away, then binds to the cofactor. Both the product and the filled cofactor then fall off the enzyme.
The loaded cofactor binds to the active site of another enzyme. Then another substrate comes along and the molecular fragment carried by the cofactor is added to the substrate and converting it into product. Both the product and empty cofactor fall off the enzyme.
The cofactor is now ready to repeat the process.
Molecular structure of one of the cofactors
Apoenzymes and holoenzymes
Coenzyme
Small organic non-protein molecules that carry chemical groups between enzymes
Not bound tightly by the enzymes as a normal part of the catalytic cycle.
Vitamins or derivatives of vitamins.
A part of the active site.
NADH coenzyme
Function of coenzyme
Binds to the active site of the enzyme and participate in catalysis.
Function as intermediate carriers of electrons, specific atoms and functional groups that are transferred in the overall reaction.
Example: the role of NAD in the transfer of electrons in certain coupled oxidation reduction reactions.
Conversion of lactate to pyruvate:
• Enzymatically catalyzed by lactate dehydrogenase
•Lactate loses 2 electrons ( becomes oxidized) and is converted into pyruvate.
• NAD+ gains 2 electrons ( is reduced) and is converted into NADH.


Conversion of lactate to pyruvate:
• Both lactate and NAD+ bind to the active site of enzyme lactate dehydrogenase and both participate in the catalytic reaction.
• In fact, catalysis could not occur unless the coenzyme NAH+ bound to the active site
Some other coenzymes with corresponding vitamins and functions:
Cosubstrate:
Loosely bound coenzymes that are required in stoichiometric amounts by enzymes
Nicotinamide adenine dinucleotide ( NAD) acts as a cosubstrate in the oxidation-reduction reaction that is catalyzed by malate dehydrogenase, one of the enzymes of citric acid cycle.
Malate + NAD+ → oxaloacetate + NADH
Prosthetic groups:
Non-protein( non-amino acid) component of an enzyme.
Tightly bound to enzymes and participate in the catalytic cycles of enzymes
Like any catalysts, an enzyme-prosthetic group complex undergoes changes during the reaction
Before catalyzing another reaction, it must return to its original state
Flavin adenine dinucleotide (FAD)
Essential ions:
Common cofactors
Activator ions:
- loosely bound to enzymes
- forming metal activated-enzymes.
Metal ions:
- tightly bound to enzymes
- forming metalloenzymes


References:
www.anaspec.com
Chemistry encyclopedia forum
Berg, Jeremy M.; Tymoczko, John L.; and Stryer, Lubert (2002). Biochemistry, 5th edition. New York: W. H. Freeman.
Horton, H. Robert; Moran, Laurence A.; Ochs, Raymond S.; Rawn, David J.; and Scrimgeour, K. Gray (2002). Principles of Biochemistry, 3rd edition. Upper Saddle River, NJ: Prentice Hall.
Voet, Donald; Voet, Judith G.; and Pratt, Charlotte (1999). Fundamentals of Biochemistry. New York: Wiley