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Enzyme Catalysis with Cofactors
It’s hard to overstate the importance of enzymes in biological systems. Almost all functions performed by a cell, including protein synthesis, DNA replication, and metabolism, depend on chemical reactions catalyzed by enzymes. Without enzymes, these processes could not occur fast nor accurate enough for life to exist. Due to the wide variety of functions served by enzymes, cells demand a wide diversity of enzymatic structure and functionality.
To increase the functionality of a cell’s array of enzymes, many enzyme-catalyzed pathways depend on the presence of non-protein components. Biochemists call these components “cofactors,” which include metal ions as well as “coenzymes,” which refers to cosubstrates and prosthetic groups. Each type of cofactor helps chemically modify a reaction, and they tend to play an irreplaceable role in most cases. For reactions that depend on cofactors, enzymes can be rendered an inactive “apoenzyme” without the presence of their cofactor. Once in contact with their cofactor, these enzyme complexes become fully active “holoenzymes”.
Enzyme Cofactors: Metal Ions
Many enzymes require metal ions in their active site to catalyze their respective chemical reaction. These metal ions often help stabilize unstable charged groups or they participate in redox reactions. Since these metals serve such important uses in enzyme catalysis, certain trace amounts of these metals form a crucial part of the diets of many organisms. Additionally, certain other metals can have toxic effects due to their effect of enzymatic action. Notable examples include Cd2+ and Hg2+, which can replace Zn2+ in enzymes dependent on that cation. However, Cd2+ and Hg2+ don’t have the same catalytic effect, resulting in dysfunctional enzymes and negative effects on the health of any organism that ingests those ions.
Perhaps the most important example of an enzyme-metal relationship involves that of DNA polymerase and Mg2+. Specifically, DNA polymerase catalyzes the formation of phosphodiester bonds between DNA nucleotides, as well as base-pairing hydrogen bonds between strands. To do this efficiently, the enzyme must stabilize the highly negatively-charged phosphates that form the backbone of the DNA strands. Magnesium cations stabilize these groups with their opposite charge, allowing DNA synthesis without structural damage or contortions to the strands.
Enzyme Cofactors: Cosubstrates
Aside from metal ions, enzymes may also depend on some organic molecule to help catalyze a reaction between their substrates. Biochemists use the term “coenzyme” to describe these organic molecules. One particular sort of coenzyme called a “cosubstrate” isn’t chemically attached to the enzyme, but rather floating transiently in the enzyme’s environment. Further, unlike other types of cofactors, cosubstrates bond to the active site of the enzyme and participate in the reaction alongside the substrate. Enzyme catalysis ends up “consuming” the cosubstrate. This means that the cosubstrate becomes chemically modified and must participate in some other reaction to regenerate it to participate in further reactions.
Nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FADH2) serve as some of the most important cosubstrates in eukaryotic organisms, due to their participation in cellular respiration. Specifically, in glycolysis and the citric acid cycle, their oxidized forms (NAD+ and FAD) become reduced by enzymes as they chemically modify glucose. Then, during the electron transport chain, the reduced cosubstrates (NADH and FADH2) become oxidized. Importantly, this powers the synthesis of ATP through oxidative phosphorylation. Of course, these newly oxidized forms can then be re-reduced to power further cellular respiration. NADH and FADH2 are good examples of cosubstrates where both their activation and inactivation serve a purpose in their enzymatic pathway.
Enzyme Cofactors: Prosthetic Groups
There also exist coenzymes that attach directly to the enzyme, rather than exist freely. Biochemists call these coenzymes “prosthetic groups,” and they tend to have strong covalent bonds with the protein of the enzyme. Like cosubstrates, prosthetic groups require regeneration to become catalytically active. Unlike cosubstrates, however, this regeneration occurs throughout their enzymatic reaction, rather than requiring a secondary reaction involving a different enzyme.
One example of an important prosthetic is the heme group associated with many different enzymes. Specifically, the heme group involves a Fe2+ ion embedded in an organic structure. The group helps catalyze important redox reactions, and thus it tends to associate with oxidoreductases. Additionally, heme groups serve purposes in non-enzyme proteins, such as hemoglobin, where heme groups bind to oxygen for transport.