Enzyme Cofactors: Mechanism and Function

Cofactors are tiny chemical compounds that bind to enzymes for activating or increasing their kinetic activity for a chemical reaction. Chemical reactions are happening all the time in living things. These reactions have a variety of purposes, one of which is to break down the food we ingest and produce energy from it. Enzymes are a class of proteins that help to make this possible. 

• These chemical reactions are accelerated (or catalyzed) by enzymes (made of protein), which work with a single substrate to catalyze a single reaction.
• For some enzymes to work as an enzyme, another non-protein molecule must be present. 
• Without these cofactors, the enzymes stay in their inactive "apoenzyme" states. 
• The enzyme becomes the active "holoenzyme" after the cofactor is included.

Key Terms: Enzyme cofactors, Cofactor and coenzyme, Enzyme, Metal ion, Organic cofactors. 

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Enzyme Cofactors

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A non-protein molecule that aids a biological reaction is called a cofactor. Cofactors may be in the form of chemical compounds, metal ions, or other molecules with advantageous properties not normally seen in amino acids. Some cofactors, such as ATP, can be created by the body, whilst other cofactors need to be supplied through diet.

• Through intermolecular interactions, this cofactor often forms a weak link with the polypeptide chains. 
• Cofactors come in two different varieties: inorganic ions, such as zinc or copper ions, which are also known as minerals, and organic molecules, or coenzymes. 
• The majority of coenzymes are either vitamins or are produced from vitamins. 
• A prosthetic group is described as being strongly covalently connected to the polypeptide chain by the cofactor. 
• Organic cofactors are frequently vitamin-based or vitamin-derived which must be eaten in trace amounts for our enzymes to work properly.

Read More: Glucose and Fructose

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Mechanism of Action

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Numerous cofactors will occupy the enzyme's active site and aid in substrate binding. An apoenzyme is a complete enzyme without a cofactor, whereas a holoenzyme is a complete enzyme with a cofactor.

• Some enzymes or enzyme complexes need a number of cofactors. 
• One metal ion and five organic cofactors, for instance, are used in the multienzyme complex pyruvate dehydrogenase at the point where the citric acid cycle and glycolysis converge. 
• These contain a metal ion (Mg²⁺), the cosubstrates nicotinamide adenine dinucleotide (NAD⁺) and coenzyme A (CoA), as well as the covalently bonded lipoamide and flavin adenine dinucleotide (FAD).
• Basic mechanism of the enzyme (E)-substrate (S) reaction looks like–

E + S ⇔ ES ⇔ EP ⇔ E + P

Here, P is denoted as the product.

• Two hypotheses are proposed for the mechanism of action Lock and key hypothesis and the Induced fit hypothesis.
• The Lock-and-Key Hypothesis states that the unbound enzyme's active site is complementary in form to the substrate.
• The Induced-Fit Hypothesis states that the flexible enzyme's active site adopts a complementary shape to the substrate only after it has been bound.

Read More: Nucleotide and Nucleoside

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Enzyme Cofactor Function

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Enzymes use cofactors to alter the shape of the active site or to supply chemical groups that are needed to promote or control enzymatic activity but are absent from the enzyme itself. 

• These chemical groups can be applied in a variety of ways, such as boosting substrate affinities.
• It is also utilized in stabilizing intermediate products inside the active site.
• Also used in adding chemical groups to an enzyme product, or taking a chemical group off the substrate. 
• Electrons, phosphate, oxygen, methyl groups, sugars, and fatty acids are typical donor/acceptor groups.

Read More: Structure of Glucose and Fructose

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Types of Enzyme Cofactors

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Various types of enzyme cofactors can be divided into a few categories– 

Vitamins: Organic substances known as vitamins serve as co-factors in vital metabolic processes. 

• Since vitamins cannot be produced by the body, they must normally be absorbed through diet. 
• Numerous vitamins work as cofactors to enable enzymes to catalyze processes, such as the synthesis of vital proteins. 
• For instance, vitamin C functions as a cofactor in the synthesis of the collagen found in connective tissue.
• The consequences of a co-factor shortage are well-illustrated by vitamin deficiencies. 
• Human body requires a wide variety of co-factors to carry out the wide variety of necessary biochemical reactions, just as there are numerous probable vitamin shortages with numerous symptoms.

Minerals: Like vitamins, minerals are substances that must be eaten into the body in order for cells to work properly. 

• The distinction is that minerals are inorganic compounds that naturally occur and are frequently found in rocks and soil.
• But vitamins are organic molecules—molecules containing carbon—that are frequently generated by other living things.
• Plants frequently provide us with minerals by absorbing them from the soil through their roots along with water. 
• Rarely, vitamin-deficient individuals may feel the impulse to eat specific types of soil in order to directly absorb the minerals from the soil.
• Copper is required for the activity of a few key liver enzymes that break down toxins, iron.
• Break down of such toxins is required for the activity of a few key metabolic enzymes, magnesium. 
• This is again required for the activity of DNA polymerase and other enzymes, and zinc, which is also required for the activity of DNA polymerase and a few key liver enzymes.

Organic Non-Vitamin Cofactors: Some cofactors are organic materials that aren't considered to be enzymes. Some of them might be produced by our own bodies, making them ineligible as vitamins.

• Coenzyme Q, an important component of the mitochondrial transport chain, and heme, a complex iron-containing compound required for our blood cells to carry oxygen throughout our bodies.
• This is an example of organic non-vitamin cofactors. 
• ATP is an essential cofactor for many biochemical processes, transferring energy to numerous enzymes, transport proteins, and more.

Read More: Hormones

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Examples of Cofactors

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Thiamine (Vitamin B3): A vitamin called thiamine is mainly present in edible seeds like beans, maize and rice. Thiamine is frequently artificially added to foods containing wheat, such as morning cereals, in an effort to enhance public health.

• Thiamine helps the body produce a variety of co-enzymes that support critical functions. 
• To degrade carbohydrates and amino acids, it is converted into thiamine pyrophosphate.
• One of the causes of Korsakoff Syndrome, a rare neurological condition seen in persons with chronic alcohol addiction, is acute thiamine deficiency. 
• In Korsakoff Syndrome, memory impairment is one of the severe symptoms brought on by acute malnutrition, thiamine deficiency, and brain damage from excessive alcohol use.

Folic Acid (Vitamin B9): Another vitamin that is increasingly frequently added to food to enhance public health is folic acid. 

• DNA, RNA, and amino acids must be produced by the body in order for cells to grow and divide.
• Folic acid is therefore especially important for expectant mothers, whose foetuses are rapidly generating new cells and tissues. 
• Folic acid deficiency can cause birth abnormalities in infants or anaemia in pregnant women who may not be able to produce enough new blood cells to keep themselves and the unborn child healthy.

Iron-Sulfur Clusters: Clusters of the ions iron and sulphur that may form stable configurations are known as iron-sulfur clusters. 

• Numerous special characteristics of these clusters that are not present in amino acids or other chemical molecules. 
• Iron-sulfur clusters are extremely beneficial for biological processes involving electron transfers because of their special characteristics. 
• More easily than less common elements like carbon, iron and sulphur can both store and release electrons.

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Things to Remember

• A cofactor is a molecule that is not a protein that aids a biological reaction.
• To improve overall health, folic acid, often known as vitamin B9, is frequently added to foods. 
• Cell growth and division require the body to create amino acids, DNA, and RNA.
• Acute thiamine deficiency is just one of the many potential causes of Korsakoff Syndrome, a rare neurological disorder that is frequently seen in people with severe alcohol addiction.
• Organic compounds known as vitamins serve as cofactors in vital metabolic processes.
• Copper is a mineral that is crucial for human health since it is required for the activity of specific liver enzymes that break down pollutants.
• Anaemia in expectant moms who may not be able to make enough new blood cells to sustain both themselves and the kid can develop from a folic acid deficit, which can also cause abnormal births in children.

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