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Enzymes: Coenzymes

What are coenzymes


Enzymes are protein catalysts that are responsible for lowering the energy barrier of many biological reactions. They function by reducing the activation energy of the reactions that they catalyse which allows the metabolic reaction to occur faster and at physiological temperatures. Enzymes are specific for one substrate due to the unique arrangement of their active sites. However many enzymes cannot function on their own, and instead require non-protein cofactors. Enzymes that require such cofactors are called apoenzymes. When the cofactor and the apoenzyme are combined a holoenzyme is produced, this holoenzyme is able to catalyse reactions.


Cofactors function by providing functional groups needed for the reaction or by slightly altering the structural conformation of the enzyme to which they are bound. This alteration allows substrates to bind more easily, making a reaction more probable. Cofactors can be prosthetic groups which are tightly bound to the enzyme, or the cofactors can be coenzymes which can be loosely bound. Coenzymes are usually released from the active site of the enzyme following a reaction. 


Role of coenzymes


Coenzymes are a type of cofactor and they are bound to enzyme active sites to aid with their proper functioning. Coenzymes which are directly involved and altered in the course of chemical reactions are considered to be a type of secondary substrate. This is because they are chemically changed as a result of the reaction unlike enzymes. However unlike the primary substrates, coenzymes can be used by a number of different enzymes and as such are not specific. For example hundreds of enzymes are able to use the coenzyme NAD. 


The function of coenzymes is to transport groups between enzymes. Chemical groups include hydride ions which are carried by coenzymes such as NAD, phosphate groups which are carried by coenzymes such as ATP and acetyl groups which are carried by coenzymes such as coenzyme A. Coenzymes which lose or gain these chemical groups in the course of the reaction are often reformed in the same metabolic pathway. For example NAD+ used in glycolysis and the citric acid cycle is replaced in the electron transport chain of respiration.


How are coenzymes made?


Due to the importance of coenzymes in chemical reactions, and due to the fact that they are used up and chemically altered by reactions, coenzymes must be continually regenerated. For example, synthesis of B vitamins is a complex, step wise process because the B vitamins have chiral centres which are complicated to synthesise. Coenzymes that are produced from B vitamins are especially important to the proper functioning of enzymes involved with regulation of metabolism and with the release of energy from food. Important B vitamins that are used as large components of coenzymes include riboflavin, niacin, biotin, pantothenic acid, B6, folate and B12. For example riboflavin, or vitamin B2 is used as a large component of FAD and FADH, and niacin is an important component of NAD and NADH. 


However vitamins cannot be made by the body, but instead they must be consumed in the diet. Therefore vitamins are essential components of the diet. Although the human body uses more than its own body weight in ATP, not as much of the vitamin that is used to produce the coenzyme is needed to be consumed. This is because the body is able to use the vitamins very instensively through regeneration.


Adenosine triphosphate (ATP)


The function of ATP is to transport chemical energy within cells for metabolism, and as such ATP is often referred to as the energy currency of cells. 


Adenosine triphosphate is composed of an adenine nucleotide base, a ribose sugar and three phosphate groups. Energy can be released from ATP when the terminal phosphate group is released in a hydrolysis reaction. This is because the energy of ATP is held in the bonds between the phosphate groups and when the bonds are broken it is accompanied by a release of energy. 


Nicotinamide adenine dinucleotide (NAD)


NAD is composed of two nucleotides, adenine and nicotinamide. The nucleotides are held together by a pair of phosphate groups which act as a bridge and are also bonded to a ribose sugar each. The function of NAD is to carry electrons from one enzyme controlled reaction to another. As such NAD is involved with redox reactions because substrates are either oxidised, in which they lose electrons or are reduced in which they gain electrons. NAD is either found as NAD+, which is an oxidising agent and is involved with accepting electrons from other molecules, or NADH which is used as a reducing agent to donate electrons to other molecules. 


Flavin adenine dinucleotide (FAD)

FAD is composed of an adenine nucleotide, a ribose sugar and two phosphate groups. FAD can also exist as a monophosphate and is called flavin adenine monophosphate (FMN). The primary role of FAD is in oxidative phosphorylation. FAD is involved with redox reactions and like NAD, FAD can exist in two redox states; FAD and FADH. The two states are interconvertable as a result of the addition or removal of electrons.


This is possible because FAD is able to accept hydride ions with their electron pairs. For example, FAD is a coenzyme used by the enzyme succinate dehydrogenase to help catalyse a reaction. The role of FAD in this reaction is to accept two electrons from succinate which results in the production of fumarate. FAD is reduced to FADH2 but remains tightly bound to succinate dehydrogenase. No further reactions can occur until FAD is regenerated.


Coenzyme A


Coenzyme A is not tightly bound to the enzymes to which it is associated and is able to freely be released. It plays an important role in the metabolism of protiens, carbohydrates and fats which are important reactions that allow the energy from food to be released. For example coenzyme A is required for the oxidation of pyruvate in the citric acid cycle. 


In addition coenzyme A is involved with acetylation reactions. These reactions are important in proper protein function and as a result many of the proteins in the body have undergone such modification reactions in which an acetate group is added to the protein. The acetate group is donated from coenzyme A. The addition of an acetate group alters the 3D structure of the protiens to which it is added and as a result thier function is also altered. In some cases a long chain fatty acid is also donated to the protien. This addition is needed for the cell signalling properties of various membrane protiens. 


Acetate groups from coenzyme A are also added to various substrates in reactions involved with gene expression and cell division. Coenzyme A is also important in the synthesis of cholesterol and steroid hormones, and is required for the detoxification of a range of harmful drugs that can accumulate in the liver. 


Alcohol dehydrogenase


Alcohol dehydrogenase (ADH) is an enzyme which uses NAD+ as a coenzyme. ADH has two binding regions, one where the primary substrate, ethanol binds and one where the coenzyme, NAD+ is able to bind. 


The enzyme is responsible for the conversion of ethanol to ethanal. The reaction is an oxidation- reduction reaction and results in the removal of two hydrogen ions and two electrons from ethanol. The hydrogen ions and electrons are added to NAD+ which converts the coenzyme to NADH + H+. This is the first reaction involved with the metabolism of ethanol. 



  • Stamp, S. (2012) Alcohol dehydrogenase. Biochemistry Chapter.
  • Becker, W. Kleinsmith, L.J. Hardin, J. Bertoni, G.P. (2008) The World of the Cell, Benjamin Cummings.
  • Price N.C., Stevens L., 1999. Fundamentals of Enzymology, 3rd Ed., Oxford University Press, New York.

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