Enzymes as Biological Catalysts - Enzymes - MCAT Biochemistry Review

MCAT Biochemistry Review

Chapter 2: Enzymes

2.2 Mechanisms of Enzyme Activity

While enzyme mechanisms will vary depending on the reaction that is being catalyzed, they tend to share some common features. Enzymes may act to provide a favorable microenvironment in terms of charge or pH, stabilize the transition state, or bring reactive groups nearer to one another in the active site. The formation of the enzyme–substrate complex in the active site of an enzyme is the key catalytic activity of the enzyme, which reduces the activation energy of the reaction as described above. This interaction between a substrate and the active site of an enzyme also accounts for the selectivity and some regulatory mechanisms of enzymes.


The molecule upon which an enzyme acts is known as its substrate. The physical interaction between these two is referred to as the enzyme–substrate complex. The active site is the location within the enzyme where the substrate is held during the chemical reaction, as shown in Figure 2.2.

Figure 2.2. Reaction Catalysis in the Active Site of an Enzyme This transferase has catalyzed the formation of a bond between two substrate molecules.

The active site assumes a defined spatial arrangement in the enzyme–substrate complex, which dictates the specificity of that enzyme for a molecule or group of molecules. Hydrogen bonding, ionic interactions, and transient covalent bonds within the active site all stabilize this spatial arrangement and contribute to the efficiency of the enzyme. Two competing theories explain how enzymes and substrates interact, but one of the two is better supported than the other.

Lock and Key Theory

The lock and key theory is aptly named. It suggests that the enzyme's active site (lock) is already in the appropriate confirmation for the substrate (key) to bind. As shown in Figure 2.3, the substrate can then easily fit into the active site, like a key into a lock, or a hand into a glove. No alteration of the tertiary or quaternary structure is necessary upon binding of the substrate.

Figure 2.3. Lock and Key Theory vs. Induced Fit Model for Enzyme Catalysis

Induced Fit Model

The more scientifically accepted theory is the induced fit model; this is the one you are more likely to see on Test Day. Imagine that the enzyme is a foam stress ball, and the substrate is a frustrated MCAT student's hand. What's the desired interaction? The student wants to release some stress and relax. As his hand squeezes the ball, both change conformation. The ball is no longer spherical and his hand is no longer flat because they adjust to fit each other well. In this case, the substrate (the student) has induced a change in the shape of the enzyme (the stress ball). This interaction requires energy, and therefore, this part of the reaction is endergonic. Once the student lets go of the stress ball, we have our desired product: a relaxed, more confident test-taker. Letting go of the stress ball is pretty easy and doesn't require extra energy; so, this part of the reaction is exergonic. Just like enzymes, foam stress balls return to their original shape once their crushers (substrates) let go of them. On a molecular level, demonstrated in Figure 2.3, the induced fit model starts with a substrate and an enzyme active site that don't seem to fit together. However, once the substrate is present and ready to interact with the active site, the molecules find that the induced form, or transition state, is more comfortable for both of them. Thus, the shape of the active site becomes truly complementary only after the substrate begins binding to the enzyme. Similarly, a substrate of the wrong type will not cause the appropriate conformational shift in the enzyme. Thus, the active site will not be adequately exposed, the transition state is not preferred, and no reaction occurs.


Many enzymes require nonprotein molecules called cofactors or coenzymes to be effective. These cofactors and coenzymes tend to be small in size so they can bind to the active site of the enzyme and participate in the catalysis of the reaction, usually by carrying charge through ionization, protonation, or deprotonation. Cofactors and coenzymes are usually kept at low concentrations in cells, so they can be recruited only when needed. Enzymes without their cofactors are called apoenzymes, whereas those containing them are holoenzymes. Cofactors are attached in a variety of ways, ranging from weak noncovalent interactions to strong covalent ones. Tightly bound cofactors or coenzymes that are necessary for enzyme function are known as prosthetic groups.


Deficiencies in vitamin cofactors can result in devastating disease. Thiamine is an essential cofactor for several enzymes involved in cellular metabolism and nerve conduction. Thiamine deficiency, often a result of excess alcohol consumption, results in diseases including Wernicke–Korsakoff syndrome. In this disorder, patients suffer from a variety of neurologic deficits, including delirium, balance problems, and, in severe cases, the inability to form new memories.

Cofactors and coenzymes are topics that we are likely to see on Test Day, so they are important to know. Cofactors are generally inorganic molecules or metal ions, and are often ingested as dietary minerals. Coenzymes are small organic groups, the vast majority of which are vitamins or derivatives of vitamins such as NAD+, FAD, and coenzyme A. The water-soluble vitamins include the B complex vitamins and ascorbic acid (vitamin C), and are important coenzymes that must be replenished regularly because they are easily excreted. The fat-soluble vitamins—A, D, E, and K—are better regulated by partition coefficients, which quantify the ability of a molecule to dissolve in a polar vs. nonpolar environment. Enzymatic reactions are not restricted to a single cofactor or coenzyme. For example, metabolic reactions often require magnesium, NAD+ (derived from vitamin B3), and biotin (vitamin B7) simultaneously.


Vitamins come in two major classes: fat- and water-soluble. This is important to consider in digestive diseases, where different parts of the gastrointestinal tract may be affected by different disease processes. Because different parts of the gastrointestinal tract specialize in the absorption of different types of biomolecules, loss of different parts of the gastrointestinal tract or its accessory organs may result in different vitamin deficiencies. The digestive system is discussed in Chapter 9 of MCAT Biology Review.

The MCAT is unlikely to expect memorization of the B vitamins; however, familiarity with their names may make biochemistry passages easier on Test Day:

· B1: thiamine

· B2: riboflavin

· B3: niacin

· B5: pantothenic acid

· B6: pyridoxal phosphate

· B7: biotin

· B9: folic acid

· B12: cyanocobalamin

MCAT Concept Check 2.2:

Before you move on, assess your understanding of the material with these questions.

1. How do the lock and key theory and induced fit model differ?

Lock and Key

Induced Fit

2. What do cofactors and coenzymes do? How do they differ?