Cofactor Definition
A cofactor is a non-protein chemical compound or metallic ion that is required for an enzyme’s role as a catalyst. It can be considered a “helper molecule” that assists in biochemical transformations. Cofactors can be divided into two types: coenzymes and prosthetic groups.
Coenzymes are organic molecules that are often derived from vitamins, while prosthetic groups are non-protein molecules that are tightly bound to enzymes. Cofactors are essential for the action of a large molecule, such as an enzyme, and without them, the protein component of the enzyme would no longer have catalytic activity.
Function of Cofactors
Cofactors are non-protein chemical compounds or metallic ions that are required for an enzyme’s role as a catalyst. They can be considered “helper molecules” that assist in biochemical transformations.
Many enzymes are simple proteins consisting entirely of one or more amino acid chains, while others contain a nonprotein component called a cofactor that is necessary for the enzyme’s proper functioning.
Cofactors can be divided into two major groups: organic cofactors, such as flavin or heme, and inorganic cofactors, such as the metal ions Mg2+, Cu+, Mn2+, and iron-sulfur clusters.
Organic cofactors are often vitamins or made from vitamins, and many contain the nucleotide adenosine monophosphate (AMP) as part of their structures, such as ATP, coenzyme A, FAD, and NAD+. This common structure may reflect a common evolutionary origin as part of ribozymes in an ancient RNA world.
Coenzymes are a type of cofactor that are small, non-protein organic molecules that carry chemical groups between enzymes, such as NAD and FAD. They form easily removed loose bonds with enzymes.
A cofactor is a non-protein chemical compound that tightly and loosely binds with an enzyme or other protein molecules. Cofactors can be further divided into prosthetic groups and coenzymes.
Prosthetic groups are cofactors that are firmly bound to the apoenzyme and cannot be removed without denaturing the latter, while coenzymes are cofactors that are bound loosely to the apoenzyme and can be readily separated from it. Coenzymes take part in the catalyzed reaction, are modified during the reaction, and may be regenerated in subsequent reactions.
Types of Cofactor
Vitamins
Enzyme cofactors are non-protein molecules that are essential for the proper functioning of enzymes. There are two types of cofactors: inorganic ions and organic molecules known as coenzymes.
Most coenzymes are vitamins or are derived from vitamins. Vitamins are organic compounds that are essential in very small amounts for the maintenance of normal metabolism.
Vitamins are classified into two broad categories: fat-soluble vitamins (vitamins A, D, E, and K) and water-soluble vitamins (vitamins B and C).
The B vitamins include vitamin B2 (riboflavin), vitamin B3 (niacin), biotin, folic acid, and pantothenic acid. Vitamin B2 is a precursor to flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), which are involved in oxidation-reduction reactions.
Vitamin B3 is a precursor to nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP), which are involved in oxidation-reduction reactions. Biotin is involved in carboxylation reactions, while folic acid is a carrier of one-carbon units such as the formyl group.
Pantothenic acid is a precursor to coenzyme A, which is a carrier of acyl groups. Vitamin C (ascorbic acid) is an antioxidant and is involved in the formation of collagen, a protein found in connective tissues.
Inorganic cofactors are minerals, such as zinc or copper ions. Two common cofactors that are derived from the B vitamins are NAD and FAD, which are derived from niacin and riboflavin, respectively. Cofactors can be oxidized or reduced for the enzymes to catalyze the reactions. An example of a mineral that serves as a cofactor
Minerals
An example of a mineral that serves as a cofactor is Fe2+ for proline and lysyl hydroxylases. Vitamin C (ascorbic acid) is needed to reduce iron to Fe2+ so that it can serve as a cofactor for proline and lysyl hydroxylases.
Vitamins are organic compounds that are essential in very small amounts for the maintenance of normal metabolism.
Over the past 100 years, scientists have identified and isolated 13 vitamins required in the human diet and have divided them into two broad categories: the fat-soluble vitamins (A, D, E, and K) and the water-soluble vitamins (B vitamins and vitamin C).
Organic Non-Vitamin Cofactors
Organic non-vitamin cofactors are a type of cofactor that is not derived from vitamins. They are organic molecules that support biochemical reactions and are not typically present in amino acids. Examples of organic non-vitamin cofactors include heme, biotin, and coenzyme A.
Pyruvate dehydrogenase, a multienzyme complex at the convergence of glycolysis and the citric acid cycle, requires one metal ion and five organic cofactors, including covalently bound lipoamide.
These cofactors are essential for the proper functioning of the enzyme. Understanding cofactors is essential for studying health at the biological level, as humans and animals may suffer life-threatening illnesses or diseases if they lack certain cofactors.
Examples of Cofactors
Thiamine (Vitamin B3)
Thiamine pyrophosphate (TPP), also known as thiamine diphosphate or cocarboxylase, is a derivative of thiamine (vitamin B1) that serves as a cofactor for enzymes involved in carbohydrate metabolism.
TPP is synthesized in the cytosol and is required in the cytosol for the activity of transketolase and in the mitochondria for the activity of pyruvate-, oxoglutarate-, and branched chain keto acid dehydrogenases.
TPP works as a coenzyme in many enzymatic reactions, such as the metabolism of carbohydrates, lipids, and branched-chain amino acids.
TPP acts as a coenzyme for the mitochondrial enzyme complexes such as α-ketoglutarate dehydrogenase and pyruvate dehydrogenase, which have a critical role in the Krebs cycle and tricarboxylic acid cycle.
In humans, the main fraction of total thiamine contains TPP (72-80%) which exists mostly in a form that is bound to TPP-dependent enzymes.
Free thiamine and TMP constitute about 20-26% of the total thiamine content and appear to be a flexible fraction of this vitamin pool that is easily transferable and transformable into TPP or TTP, depending on the requirements at the time.
Thiamine deficiency decreases the activity of these enzymes, which impairs the conversion of pyruvate to acetyl-CoA, leading to a decrease in ATP production.
Folic Acid (Vitamin B9)
Folic acid (vitamin B9) functions as a coenzyme or cosubstrate in single-carbon transfers in the synthesis of nucleic acids (DNA and RNA) and the metabolism of amino acids.
One of the most important folate-dependent reactions is the conversion of homocysteine to methionine in the synthesis of S-adenosyl-methionine, an important methyl donor.
The folate cofactor, N5-methyltetrahydrofolate, donates its methyl group to a vitamin B12-dependent enzyme, methionine synthase, which recycles homocysteine back to methionine.
This process is important for the supply of methyl groups to the methylation cycle, which uses methionine and makes homocysteine.
Iron-Sulfur Clusters
Iron-sulfur clusters are polynuclear inorganic cofactors composed of clusters of ferric (Fe3+) and ferrous (Fe2+) cations and sulfide (S2−) anions.
They are essential cofactors that mediate electron transfer within the mitochondrial respiratory chain. The Fe-S cluster pathways that function within the respiratory complexes are highly conserved between bacteria and the mitochondria of eukaryotic cells.
Iron (Fe2+) is a cofactor for proline and lysyl hydroxylases. Vitamin C (ascorbic acid) is needed to reduce iron to Fe2+ so that it can serve as a cofactor for proline and lysyl hydroxylases. Most inorganic cofactors are minerals, and iron is one of them.
