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I've just been wondering what are the differences between the two and I can't seem to find a formal delineation.

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Enzyme cofactors are a collective name of all the chemical compunds or elements associated with the enzyme to increase its efficiency. There are mainly two types- inorganic ions and organic compounds. Inorganic ions are also known as enzyme activators (Cl ion in salivary amylase). Organic compunds are again divided into two- co-enzymes and prosthetic groups. Co-enzymes are loosely associated with the enzyme. They can be removed from the enzyme and undergo cyclic reactions to again combine with enzyme (EX: NAD, NADP). But prosthetic groups are tightly associated with enzyme molecules(EX : FAD). Hope this helps.

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A cofactor is a non-protein chemical compound. It is bound to the protein
Coenzymes are cofactors that are bound to an enzyme loosely.
Coenzymes are a special case of cofactors. (With Prosthetic groups)

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These terms, according to this paper, have not been defined consistently in textbooks. The same paper suggests the following definitions:

Prosthetic group, coenzyme and cofactor are all generally defined. Whilst a cofactor is any factor essentially required for enzyme activity or protein function, a coenzyme is the cofactor which is directly involved in enzyme catalysed reaction. A cofactor which is not directly involved in enzyme catalysis, or is associated with the function of a non-catalytic protein is not a coenzyme. A prosthetic group (covalently associated non-protein constituent required for a particular function), on the other hand, may also be termed a coenzyme if it is directly involved in catalytic reaction. A prosthetic group which is not involved in enzyme catalysed reaction but functionally essential to the enzyme or a non-catalytic protein is also called a cofactor. Coenzyme and cofactor weakly bound to enzyme or protein are however, not classified as prosthetic group.

So the prosthetic group is defined via its binding properties, the coenzyme is defined via its reaction, and a cofactor is defined via its chemical makeup. This results in lots of overlap and gray areas. A three-dimensional Venn diagram might be necessary to decide in a specific case which term or terms are applicable.

It does not help that hemoglobin, often the first example of a protein with a prosthetic group presented to students, binds to a metal via an organic molecule and is sometimes called an enzyme (but it is just an honorary enzyme).

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Cofactor is a non protein chemical compound that bound to the protein while a coenzyme is a Cofactor that bound to the enzyme

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    $\begingroup$ Your answer adds nothing new to previous answers. $\endgroup$
    – PAEP
    Commented Sep 23, 2023 at 16:20

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