2.19: Enzymes regulate reactions in several ways (but malformed enzymes can cause problems).

If not for enzymes, it is possible that nothing would ever get done. At least not in living organisms. Enzymes don’t alter the outcome of reactions, but without the chemical “nudge” they supply—often increasing reaction rates to millions of times their uncatalyzed rate—the processes necessary to sustain life could not occur.

The rate at which an enzyme catalyzes a reaction is influenced by several chemical and physical factors (FIGURE 2-43). These include:

• 1. Enzyme and substrate concentration. For a given amount of substrate, an increase in the amount of enzyme increases the rate at which the reaction occurs. Similarly, for a given amount of enzyme, an increase in the substrate concentration increases the reaction rate. In both cases, once all of the enzyme molecules are bound to substrate, or vice versa, additional enzyme or substrate no longer increases the reaction rate.
• 2. Temperature. Because increasing the temperature increases the speed of movement of molecules, reaction rates generally increase at higher temperatures. Reaction rates continue to increase only up to the optimum temperature for an enzyme. At temperatures above the optimum, reaction rates decrease as enzymes lose their shape or even denature. Enzymes from different species can have widely differing optimum temperatures.
• 3. pH. As with temperature, enzymes have an optimum pH. Above or below this pH, excess hydrogen or hydroxide ions interact with amino acid side chains in the active site. These interactions disrupt enzyme function (and sometimes structure) and decrease reaction rates.
• 4. Presence of inhibitors or activators. One of the most common ways that cells can speed up or slow down their metabolic pathways is through the binding of other chemicals to enzymes. This binding can alter enzyme shape in a way that increases or decreases the enzyme’s activity. Inhibitors reduce enzyme activity and come in two types. Competitive inhibitors bind to the active site, blocking substrate molecules from the site and thus from taking part in the reaction. Noncompetitive inhibitors do not compete for the active site but, rather, bind to another part of the enzyme, altering its shape in a way that changes the structure of the active site, thus reducing or blocking its ability to bind with substrate. Often, it is the very product of a metabolic pathway that acts as an inhibitor of enzymes early in the pathway, effectively shutting off the pathway when enough of its end product has been produced.

Just as a molecule can bind to an enzyme and inhibit the enzyme’s activity, so can some cellular chemicals act as activators. Instead of their binding to the enzyme “turning it off,” their binding to the enzyme “turns it on,” altering the enzyme’s shape or structure so that it can now catalyze a reaction.

Sometimes a cell produces a protein “word” that is misspelled—that is, the sequence of amino acids is incorrect. If an enzyme is altered even slightly, the active site may change and the enzyme will no longer function (FIGURE 2-44). Slightly modified, non-functioning enzymes are responsible for a large number of diseases and physiological problems (see Section 5-9). An example is the body’s inability to break down the amino acid phenylalanine (in a condition known as phenylketonuria).

One health issue influenced by enzyme function is the condition called lactose intolerance. Normally, during digestion, the lactose in milk is broken down into its component parts, glucose and galactose (see Figure 2-42). These simple sugars are then used for energy. But some people, when they become adults, are unable to break the bond linking the two simple sugars because they no longer produce the enzyme lactase that assists in this process. Consequently, any lactose in their diet passes through their stomach and small intestine undigested. Then, when it reaches the large intestine, bacteria living there consume the lactose. The problem is that, as the bacteria break down the lactose, they produce some carbon dioxide and other gases. These gases are trapped in the intestine and lead to severe discomfort. Interestingly, in regions of the world with long traditions of pastoralism (raising and consuming livestock), lactose intolerance is much rarer than in other parts of the world. Only about 10% of people from Denmark or Sweden have lactose intolerance, but among people from China, which has historically been largely non-pastoral, the vast majority of adults (more than 80% according to numerous published studies) are lactose intolerant.

The unpleasant symptoms of lactose intolerance can be avoided by not consuming milk, cheese, yogurt, ice cream, or any other dairy products, but they can also be avoided by taking a pill containing the enzyme lactase. It doesn’t matter how the enzyme gets into your digestive system; as long as it’s there, the lactose in the milk can be broken down.