Cofactors

Cofactors are non-protein chemical components that bind to enzymes or other proteins and are necessary for their biological activity. They can participate in catalysis directly, stabilize active-site structures, or help in substrate binding and orientation. Without these helpers, many enzymes remain inactive or work far more slowly.

Cofactors are broadly classified into inorganic and organic types. Inorganic cofactors are typically metal ions, such as magnesium, manganese, iron, zinc, and copper, which can stabilize charged intermediates, participate in redox reactions, or provide catalytic versatility. Organic cofactors, also known as coenzymes, are organic molecules often derived from vitamins. Common examples include NAD+ and NADP+ (nicotinamide adenine dinucleotide), FAD (flavin adenine dinucleotide), CoA (coenzyme A), biotin, and lipoic acid. Some cofactors are tightly bound prosthetic groups integrated into the enzyme, while others are loosely bound cosubstrates that cycle in and out during reactions.

Differentiating apoenzymes from holoenzymes helps describe their dependency on cofactors. An apoenzyme is the protein alone, lacking its cofactor; a holoenzyme includes the bound cofactor. Prototypical examples include heme as a tightly bound prosthetic group in cytochromes or the NAD+/NADP+ coenzymes that shuttle electrons. Cofactor binding can be permanent or transient, and coenzymes often participate in redox chemistry, group transfer, or electron and atom shuttling during catalysis.

Many cofactors are vitamin-derived or require vitamins for their biosynthesis and maintenance. Deficiencies in these vitamins can impair enzyme function and metabolism, illustrating the essential, interconnected nature of cofactors in cellular biology.