Many enzymes contain small molecules or metal ions that participate directly in substrate binding or in catalysis. Termed prosthetic groups, cofactors, and coenzymes, they extend the repertoire of mechanistic capabilities beyond those afforded by the functional groups present on the aminoacyl side chains of peptides.

Prosthetic Groups

Prosthetic groups are tightly and stably incorporated into a protein’s structure by covalent bonds or noncovalent forces. Examples include pyridoxal phosphate, flavin mononucleotide (FMN), flavin adenine dinucleotide (FAD), thiamin pyro phosphate, lipoic acid, biotin, and transition metals such as Fe, Co, Cu, Mg, Mn, and Zn. Metal ions that participate in redox reactions generally are bound as organometallic complexes such as the prosthetic groups heme or iron–sulfur clusters. Metals may facilitate the binding and orientation of substrates, the formation of covalent bonds with reaction intermediates (Co²⁺ in coenzyme B₁₂), or by acting as Lewis acids or bases to render substrates more electrophilic (electron-poor) or nucleophilic (electron-rich), and hence more reactive.

Cofactors Associate Reversibly with Enzymes or Substrates

 Cofactors serve functions similar to those of prosthetic groups and overlap with them. The major difference between the two is operational, not chemical. Cofactors bind weakly and transiently to their cognate enzymes or substrates, forming dis sociable complexes. Therefore, unlike associated prosthetic groups, cofactors must be present in the surrounding environment to promote complex formation in order for catalysis to occur. Metal ions form the most numerous class of cofactors. Enzymes that require a metal ion cofactor are termed metal activated enzymes to distinguish them from the metalloen zymes for which bound metal ions serve as prosthetic groups. It is estimated that one-third of all enzymes fall into one of these two groups.

Many Coenzymes, Cofactors, & Prosthetic Groups Are Derivatives of B Vitamins

The water-soluble B vitamins supply important components of numerous coenzymes. Nicotinamide is a component of the redox coenzymes NAD and NADP (Figure 1); riboflavin is a component of the redox coenzymes FMN and FAD; pan tothenic acid is a component of the acyl group carrier coenzyme A. As its pyrophosphate thiamin participates in the decarboxylation of α-keto acids while folic acid and cobamide coenzymes function in one-carbon metabolism. In addition, several coenzymes contain the adenine, ribose, and phosphoryl moieties of AMP or ADP (see Figure 1).

Fig1. Structure of NAD⁺ and NADP⁺ .For NAD⁺, OR = - OH. For NADP⁺, - OR = -OPO₃^2-

Coenzymes Serve as Substrate Shuttles

Coenzymes serve as recyclable shuttles that transport many substrates from one point within the cell to another. The function of these shuttles is twofold. First, they stabilize species such as hydrogen atoms (FADH₂ ) or hydride ions (NADH) that are too reactive to persist for any significant time in the presence of the water, oxygen, or the organic molecules that permeate cells. Second, they increase the number of points of contact between substrate and enzyme, which increases the affinity and specificity with which small chemical groups such as acetate (coenzyme A), glucose (UDP), or hydride (NAD⁺) are bound by their target enzymes. Other chemical moieties transported by coenzymes include methyl groups (folates) and oligosaccharides (dolichol).