MCAT Biochemistry Review
Chapter 2: Enzymes
There is an obesity epidemic in the United States that is paralleled by an increase in high blood pressure, or hypertension. This is extremely relevant to medical students because hypertension increases the risk of stroke, heart failure, and kidney failure.
Each year, physicians encourage millions of Americans to improve their diets, add exercise to their daily regimens, or even take prescription drugs to control their hypertension. Many of these anti-hypertensive medications are called ACE (angiotensin-converting enzyme) inhibitors. In healthy patients, ACE catalyzes a reaction that converts a peptide called angiotensin I to angiotensin II. The angiotensin II peptide then not only directly causes constriction of the blood vessels to raise blood pressure, but also stimulates the release of the hormone aldosterone, which activates the kidneys to reabsorb more water back into the bloodstream. The increase in blood volume also increases blood pressure. Physicians take advantage of this complicated pathway with a straightforward solution: stop the pathway early by inhibiting ACE, and blood pressure will decrease.
Enzymes are crucial proteins that dramatically increase the rate of biological reactions. They're used to regulate homeostatic mechanisms in every organ system and are highly regulated themselves by environmental conditions, activators, and inhibitors. These regulators may be naturally occurring or may be given as a drug, such as the ACE inhibitors used to treat hypertension. Some enzymes are kept in an inactivated form called a zymogen and are only activated as needed. In this chapter, we'll learn about how enzymes work and how different conditions influence their activity. We'll also see how enzymes are regulated, which will help us tie together concepts about every organ system and metabolic process we learn about for the MCAT.
2.1 Enzymes as Biological Catalysts
Enzymes are incredibly important as biological catalysts. Catalysts do not impact the thermodynamics of a biological reaction; that is, the ΔHrxn and equilibrium position do not change. Instead, they help the reaction proceed at a much faster rate. As a catalyst, the enzyme is not changed during the course of the reaction. Enzymes increase the reaction rate of a process by a factor of 100, 1000 or even 1,000,000,000,000 (1012) times when compared to the uncatalyzed reaction. Without this increase, we wouldn't be alive. Table 2.1 summarizes the key points to remember about enzymes.
Lower the activation energy
Increase the rate of the reaction
Do not alter the equilibrium constant
Are not changed or consumed in the reaction (which means that they will appear in both the reactants and products.)
Are pH- and temperature-sensitive, with optimal activity at specific pH ranges and temperatures
Do not affect the overall ΔG of the reaction
Are specific for a particular reaction or class of reactions
Table 2.1. Key Features of Enzymes
Enzymes are picky. The molecules upon which an enzyme acts are called substrates; a given enzyme will only catalyze a single reaction or class of reactions with these substrates, a property known as enzyme specificity. For example, urease only catalyzes the breakdown of urea.Chymotrypsin, on the other hand, can cleave peptide bonds around the amino acids phenylalanine, tryptophan, and tyrosine in a variety of polypeptides. Although those amino acids aren't identical, they all contain an aromatic ring, which makes chymotrypsin specific for a class of molecules.
Enzymes can be classified into six categories, based on their function or mechanism. We'll review each type of enzyme and give examples of those that you are most likely to see on Test Day. If you encounter an unfamiliar enzyme on the MCAT, keep in mind that most enzymes have descriptive names ending in the suffix – ase: lactase, for example, breaks down lactose.
Oxidoreductases catalyze oxidation–reduction reactions, that is, the transfer of electrons between biological molecules. They often have a cofactor that acts as an electron carrier, such as NAD+ or NADP+. In reactions catalyzed by oxidoreductases, the electron donor is known as thereductant, and the electron acceptor is known as the oxidant. Enzymes with dehydrogenase or reductase in their names are usually oxidoreductases. Enzymes in which oxygen is the final electron acceptor often include oxidase in their names.
The convention for naming reductants and oxidants of oxidoreductases is the same as the convention for naming reducing agents and oxidizing agents in general and organic chemistry. This is a good time to brush up on oxidation–reduction reactions if you haven't seen them in a while—they're covered in Chapter 11 of MCAT General Chemistry Review and Chapter 4 of MCAT Organic Chemistry Review.
Transferases catalyze the movement of a functional group from one molecule to another. For example, in protein metabolism, an aminotransferase can convert aspartate and α-ketoglutarate, as a pair, to glutamate and oxaloacetate by moving the amino group from aspartate to α-ketoglutarate. Most transferases will be straightforwardly named, but remember that kinases are also a member of this class. Kinases catalyze the transfer of a phosphate group, generally from ATP, to another molecule.
Hydrolases catalyze the breaking of a compound into two molecules using the addition of water. In common usage, many hydrolases are named only for their substrate. For example, one of the most common hydrolases you will encounter on the MCAT is a phosphatase, which cleaves a phosphate group from another molecule. Other hydrolases include peptidases, nucleases, and lipases, which break down proteins, nucleic acids, and lipids, respectively.
Lyases catalyze the cleavage of a single molecule into two products. They do not require water as a substrate and do not act as oxidoreductases. Because most enzymes can also catalyze the reverse of their specific reactions, the synthesis of two molecules into a single molecule may also be catalyzed by a lyase. When fulfilling this function, it is common for them to be referred to as synthases.
Isomerases catalyze the rearrangement of bonds within a molecule. Some isomerases can be can also be classified as oxidoreductases, transferases, or lyases, depending on the mechanism of the enzyme. Keep in mind that isomerases catalyze reactions between stereoisomers as well as constitutional isomers.
Ligases catalyze addition or synthesis reactions, generally between large similar molecules, and often require ATP. Synthesis reactions with smaller molecules are generally accomplished by lyases. Ligases are most likely to be encountered in nucleic acid synthesis and repair on Test Day.
Major Enzyme Classifications: LI'L HOT
IMPACT ON ACTIVATION ENERGY
Recall that thermodynamics relates the relative energy states of a reaction in terms of its products and reactants. An endergonic reaction is one that requires energy input (ΔG > 0), whereas an exergonic reaction is one in which energy is given off (ΔG < 0). Remember that endo– means “in” and exo– means “out,” so endergonic reactions take in energy as they proceed, whereas exergonic reactions release energy as they proceed. We can look at the reaction diagram in Figure 2.1 to see this demonstrated more clearly.
Figure 2.1. Exergonic Reaction Diagram The activation energy required for a catalyzed reaction is lower than that of an uncatalyzed reaction while the ΔG (and ΔH) remains the same.
The reaction shown in Figure 2.1 is spontaneous. Note that the ΔG for this reaction is negative. A very important characteristic of enzymes is that they do not alter the overall free energy change for a reaction, nor do they change the equilibrium of a reaction. Rather, they affect the rate (kinetics) at which a reaction occurs; thus, they can affect how quickly a reaction gets to equilibrium but not the actual equilibrium state itself. For example, a reaction could take years to approach equilibrium without an enzyme. In comparison, with the enzyme, equilibrium might be attained within seconds. Enzymes ensure that many important reactions can occur in a reasonable amount of time in biological systems. Recall that enzymes, as catalysts, are unchanged by the reaction. What is the functional consequence of this? Far fewer enzymes are required relative to the overall amount of substrate because one enzyme can act on many, many molecules of substrate over time.
Catalysts exert their effect by lowering the activation energy of a reaction; in other words, they make it easier for the substrate to reach the transition state. Imagine having to walk to the other side of a tall hill. The only way to get there is to climb to the top of the hill and then walk down the other side—but wouldn't it be easier if the top of the hill was cut off so one wouldn't have to climb so high? That's exactly what catalysts do for chemical reactions when they make it easier for substrates to achieve their transition state. Most reactions catalyzed by enzymes are technically reversible, although that reversal may be extremely energetically unfavorable and therefore essentially nonexistent.
MCAT Concept Check 2.1:
Before you move on, assess your understanding of the material with these questions.
1. How do enzymes function as biological catalysts?
2. What is enzyme specificity?
3. What are the names and main functions of the six different classes of enzymes?
4. In what ways do enzymes affect the thermodynamics vs. the kinetics of a reaction?