Human Physiology, 14th edition (2016)

94 Chapter 4

increases. Eventually, however, a point will be reached where

additional increases in substrate concentration do not result

in comparable increases in reaction rate. When the rela-

tionship between substrate concentration and reaction rate

reaches a plateau of maximum velocity, the enzyme is said

to be saturated. If we think of enzymes as workers in a plant

that converts a raw material (say, metal ore) into a product

(say, iron), then enzyme saturation is like the plant working

at full capacity, with no idle time for the workers. Increasing

the amount of raw material (substrate) at this point cannot

increase the rate of product formation. This concept is illus-

trated in figure 4.6.

Some enzymatic reactions within a cell are reversible, with

both the forward and the backward reactions catalyzed by the

same enzyme. The enzyme carbonic anhydrase, for example,

is named because it can catalyze the following reaction:

H^2 C O^3 → H^2 O 1 C O^2

The same enzyme, however, can also catalyze the reverse

reaction:

H^2 O 1 CO^2 → H^2 C O^3

The two reactions can be more conveniently illustrated by a

single equation with double arrows:

H^2 O 1 C O^2  H^2 C O^3

The direction of the reversible reaction depends on the

relative concentrations of the molecules to the left and right

of the arrows. If the concentration of CO 2 is very high (as it

is in the tissues), the reaction will be driven to the right. If

the concentration of CO 2 is low and that of H 2 CO 3 is high (as

it is in the lungs), the reaction will be driven to the left. The

principle that reversible reactions will be driven from the side

of the equation where the concentration is higher to the side

where the concentration is lower is known as the law of mass

action.

Coenzymes are organic molecules, derived from water-
soluble vitamins such as niacin and riboflavin, that are needed
for the function of particular enzymes. Coenzymes participate
in enzyme-catalyzed reactions by transporting hydrogen atoms
and small molecules from one enzyme to another. Examples
of the actions of cofactors and coenzymes in specific reactions
will be given in the context of their roles in cellular metabo-
lism in section 4.3.

Enzyme Activation

There are a number of important cases in which enzymes are
produced as inactive forms. In the cells of the pancreas, for
example, many digestive enzymes are produced as inactive
zymogens, which are activated after they are secreted into the
intestine. Activation of zymogens in the intestinal lumen (cav-
ity) protects the pancreatic cells from self-digestion.
In liver cells, as another example, the enzyme that cata-
lyzes the hydrolysis of stored glycogen is inactive when it is
produced, and must later be activated by the addition of a phos-
phate group. A different enzyme, called a protein kinase, cata-
lyzes the addition of the phosphate group to that enzyme. This
enzyme activation occurs between meals (in a fasting state),
when the breakdown of glycogen to glucose allows the liver
to secrete glucose into the blood. After a carbohydrate meal,
when glucose enters the blood from the intestine, the liver
enzyme that hydrolyzes glycogen is inactivated by the removal
of its phosphate group (by yet a different enzyme). This allows
glycogen breakdown in the liver to be replaced by glycogen
synthesis.
The activation/inactivation of the enzyme in this exam-
ple is achieved by the process of phosphorylation/dephos-
phorylation. Many other enzymes are regulated in a similar
manner, but some are activated by binding to small, regula-
tory organic molecules. For example, the enzyme protein
kinase is activated when it binds to cyclic AMP (cAMP), a
second-messenger molecule (chapter 6) discussed in rela-
tion to neural and endocrine regulation in chapters 7 and 11,
respectively.
Enzyme activity is also regulated by the turnover of
enzyme proteins. This refers to the breakdown and resyn-
thesis of enzymes. Enzymes can be reused indefinitely after
they catalyze reactions, but—as discussed in chapter 3—
enzymes are degraded within lysosomes and proteosomes.
Thus, their activities will end unless they are also resynthe-
sized. Enzyme turnover allows genes to alter the enzyme
activities (and thus metabolism) of the cell as conditions
change.

Substrate Concentration and

Reversible Reactions

At a given level of enzyme concentration, the rate of prod-
uct formation will increase as the substrate concentration

Figure 4.6 The effect of substrate concentration

on the rate of an enzyme-catalyzed reaction. When

the reaction rate is at a maximum, the enzyme is said to be

saturated.

Maximum rate

Saturation

Substrate concentration

Reaction rate